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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Hereditary Spastic Paraplegia Overview - GeneReviews&reg; - NCBI Bookshelf</title>
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id="jr-fip-next" class="wsprkl btn" title="Jump to next match">&#9654;</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK1509_"><span class="title" itemprop="name">Hereditary Spastic Paraplegia Overview</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: Hereditary Spastic Paraparesis, Strumpell-Lorrain Syndrome</div><p class="contribs">Hedera P.</p><p class="fm-aai"><a href="#_NBK1509_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 41 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="hsp.Summary" itemprop="description"><h2 id="_hsp_Summary_">Summary</h2><p>The purpose of this overview is to:</p><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><p class="no_top_margin">Describe the <a href="#hsp.Clinical_Characteristics_and_Recomme">clinical characteristics</a> of hereditary spastic paraplegia and recommended treatment.</p></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><p class="no_top_margin">Review the <a href="#hsp.Causes_of_Hereditary_Spastic_Paraple">causes</a> of hereditary spastic paraplegia.</p></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><p class="no_top_margin">Consider the <a href="#hsp.Differential_Diagnosis_of_Hereditary">differential diagnosis</a> of hereditary spastic paraplegia.</p></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><p class="no_top_margin">Provide an <a href="#hsp.Evaluation_Strategies_to_Identify_th">evaluation strategy</a> to identify the genetic cause of hereditary spastic paraplegia in a proband.</p></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><p class="no_top_margin">Inform <a href="#hsp.Genetic_Counseling">genetic counseling</a> of family members of a proband with hereditary spastic paraplegia.</p></dd></dl></dl>
</div><div id="hsp.Clinical_Characteristics_and_Recomme"><h2 id="_hsp_Clinical_Characteristics_and_Recomme_">1. Clinical Characteristics and Recommended Treatment: Hereditary Spastic Paraplegia</h2><p><b>The predominant signs and symptoms of hereditary spastic paraplegia (HSP)</b> are lower-extremity weakness and spasticity.</p><p><b>Neurologic examination.</b> Individuals with HSP demonstrate the following:</p><ul><li class="half_rhythm"><div>Bilateral lower-extremity spasticity (maximal in hamstrings, quadriceps, adductors, and gastrocnemius-soleus muscles) and weakness (maximal in the iliopsoas, hamstring, and tibialis anterior muscles). Spasticity and weakness are variable. Some individuals have spasticity and no demonstrable weakness, whereas others have spasticity and weakness in approximately the same proportions.</div></li><li class="half_rhythm"><div>Lower-extremity hyperreflexia and extensor plantar responses</div></li><li class="half_rhythm"><div>Often, mildly impaired vibration sensation in the distal lower extremities</div></li></ul><p>
<b>Symptom onset</b>
</p><ul><li class="half_rhythm"><div><b>Early onset.</b> When symptoms begin in very early childhood, they may be non-progressive and resemble spastic diplegic cerebral palsy.</div></li><li class="half_rhythm"><div><b>Later onset.</b> When symptoms begin in later childhood or after they usually progress slowly and steadily. After a number of years, it is not usual for individuals with progressively worsening gait to experience a "functional plateau" (i.e., the rate of further worsening of gait impairment is similar to that attributable to age).</div></li></ul><p><b>Classification.</b> HSP is classified clinically as "uncomplicated" (nonsyndromic) or "complicated" (syndromic).</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Uncomplicated (or "pure") HSP</b> is characterized by neurologic impairment limited to progressive lower-extremity spastic weakness, hypertonic urinary bladder disturbance, and mild diminution of lower-extremity vibration sensation [<a class="bibr" href="#hsp.REF.harding.1983.1151" rid="hsp.REF.harding.1983.1151">Harding 1983</a>]. Individuals with uncomplicated HSP experience the following:</div><ul><li class="half_rhythm"><div>Difficulty walking (may either be non-progressive or worsen insidiously)</div></li><li class="half_rhythm"><div>Often, the need for canes, walkers, or wheelchairs</div></li><li class="half_rhythm"><div>Possible urinary urgency and lower-extremity paresthesias</div></li><li class="half_rhythm"><div>Typically, normal strength and dexterity of the upper extremities</div></li><li class="half_rhythm"><div>No involvement of speech, chewing, or swallowing</div></li></ul><div class="half_rhythm">Though symptoms may be disabling, life span is not shortened.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Complicated HSP</b> is characterized by the impairments present in uncomplicated HSP <b>plus</b> other system involvement or other neurologic findings including any of the following:*</div><ul><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Seizures</div></li><li class="half_rhythm"><div>Intellectual disability</div></li><li class="half_rhythm"><div>Dementia</div></li><li class="half_rhythm"><div>Muscle atrophy</div></li><li class="half_rhythm"><div>Extrapyramidal disturbance</div></li><li class="half_rhythm"><div>Peripheral neuropathy</div></li></ul><div class="half_rhythm">*&#x000a0;In the absence of other causes for these additional features</div></li></ul><div id="hsp.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>At present, there is no specific treatment to prevent or reverse nerve degeneration in HSP. Treatments are directed at reducing symptoms and improving balance, strength, and agility. Individuals should be evaluated periodically (annually or as needed) by a neurologist and physiatrist to assess progression and develop treatment strategies to maximize walking ability and reduce symptoms.</p><p>Current recommendations:</p><ul><li class="half_rhythm"><div>Daily regimen of physical therapy directed toward improving cardiovascular fitness, maintaining and improving muscle strength and gait, and reducing spasticity</div></li><li class="half_rhythm"><div>Occupational therapy, assistive walking devices, and ankle-foot orthotics as needed</div></li><li class="half_rhythm"><div>Drugs to reduce muscle spasticity (e.g., Lioresal<sup>&#x000ae;</sup> [oral or intrathecal], tizanidine, dantrolene, botulinum A and B toxin injections [Botox<sup>&#x000ae;</sup>, Dysport, Xeomin, or Myoblock]) and urinary urgency (e.g., oxybutynin, solifenacin, mirabegron, or intrabladder injections with Botox<sup>&#x000ae;</sup>)</div></li></ul></div></div><div id="hsp.Causes_of_Hereditary_Spastic_Paraple"><h2 id="_hsp_Causes_of_Hereditary_Spastic_Paraple_">2. Causes of Hereditary Spastic Paraplegia</h2><p><b>Genetic types of hereditary spastic paraplegia (HSP).</b> To date, more than 80 genetic types of HSP have been defined by genetic linkage analysis and identification of HSP-related gene variants. In the past, genetic loci for HSP were designated SPG (for "<i>sp</i>astic paraple<i>g</i>ia") and numbered in order of their discovery. With the identification of the causative genes at those loci, reference by clinicians and clinical labs to a specific genetic type of HSP has moved to the name of the gene rather than the locus designation. Autosomal dominant, autosomal recessive, X-linked, and maternally inherited (mitochondrial) forms of HSP have been identified.</p><p><b>Autosomal dominant HSP</b> is the most common type of HSP, found in 75%-80% of affected individuals.</p><ul><li class="half_rhythm"><div>SPG4, caused by a pathogenic variant in <i>SPAST</i>, is the most common type, accounting for approximately 40% of all autosomal dominant HSP.</div></li><li class="half_rhythm"><div>SPG3A, caused by a pathogenic variant in <i>ATL1</i>, is the second most common type of autosomal dominant HSP, accounting for approximately 10%-15% of all autosomal dominant HSP. SPG3A is the main cause of autosomal dominant HSP with early onset (occurs in &#x0003e;75% of individuals in this category).</div></li><li class="half_rhythm"><div>SPG30 (caused by a pathogenic variant in <i>KIF1A</i>) and SPG31 (caused by a pathogenic variant in <i>REEP1</i>) are both relatively common, each accounting for about 5% of all autosomal dominant HSP.</div></li><li class="half_rhythm"><div>Other types of autosomal dominant HSP with a predominantly adult onset are relatively rare and most of them account for 1% or less of all autosomal dominant HSP.</div></li></ul><p><b>Autosomal recessive HSP</b> is very heterogeneous, with an ever-growing list of newly identified genes. Many new causes of autosomal recessive HSP are very rare and may be limited to a single family or even a single individual. The frequency is increased in populations with a higher degree of consanguinity. AR HSP is found in an estimated 25%-30% of all individuals with HSP.</p><p>Most common types of autosomal recessive HSP are encountered in the general population:</p><ul><li class="half_rhythm"><div>SPG5A, caused by pathogenic variants in <i>CYP7B1</i>, accounts for 7.3% of all autosomal recessive HSP and 3% of apparently sporadic pure spastic paraplegia.</div></li><li class="half_rhythm"><div>SPG7, caused by pathogenic variants in <i>SPG7</i>, may account for approximately 5% of all autosomal recessive HSP.</div></li><li class="half_rhythm"><div>SPG11, caused by pathogenic variants in <i>SPG11</i>, accounts for 3%-5% of all autosomal recessive HSP but is found in 75% of individuals with all types of HSP who have radiologic signs of thin or absent corpus callosum.</div></li></ul><p><b>X-linked HSP and mitochondrial HSP</b> are the rarest genetic forms of HSP, accounting for fewer than 1%-2% of all individuals affected with HSP.</p><p><b>Other.</b> Several types of HSP (e.g., those associated with pathogenic variants in <i>ATL1</i> [<a class="bibr" href="#hsp.REF.khan.2014.1180" rid="hsp.REF.khan.2014.1180">Khan et al 2014</a>], <i>SPG7</i> [<a class="bibr" href="#hsp.REF.mcdermott.2001.467" rid="hsp.REF.mcdermott.2001.467">McDermott et al 2001</a>], and <i>ALDH18A1</i> [<a class="bibr" href="#hsp.REF.coutelier.2015.2191" rid="hsp.REF.coutelier.2015.2191">Coutelier et al 2015</a>]) may be inherited as either autosomal recessive or autosomal dominant disorders.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighspThereditaryspasticparaplegiagene"><a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobhspThereditaryspasticparaplegiagene"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hsp.T.hereditary_spastic_paraplegia_gene"><a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene">Table 1. </a></h4><p class="float-caption no_bottom_margin">Hereditary Spastic Paraplegia: Genes and Distinguishing Clinical Features &#x02013; Autosomal Dominant Inheritance </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighspThereditaryspasticparaplegiagene1"><a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_1/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobhspThereditaryspasticparaplegiagene1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hsp.T.hereditary_spastic_paraplegia_gene_1"><a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_1/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene1">Table 2. </a></h4><p class="float-caption no_bottom_margin">Hereditary Spastic Paraplegia: Genes and Distinguishing Clinical Features &#x02013; Autosomal Recessive Inheritance </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighspThereditaryspasticparaplegiagene2"><a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_2/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobhspThereditaryspasticparaplegiagene2"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hsp.T.hereditary_spastic_paraplegia_gene_2"><a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_2/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene2">Table 3. </a></h4><p class="float-caption no_bottom_margin">Hereditary Spastic Paraplegia: Genes and Distinguishing Clinical Features &#x02013; X-Linked Inheritance </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighspThereditaryspasticparaplegiagene3"><a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_3/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobhspThereditaryspasticparaplegiagene3"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hsp.T.hereditary_spastic_paraplegia_gene_3"><a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_3/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene3">Table 4. </a></h4><p class="float-caption no_bottom_margin">Hereditary Spastic Paraplegia: Gene and Distinguishing Clinical Features &#x02013; Maternal (Mitochondrial) Inheritance </p></div></div></div><div id="hsp.Differential_Diagnosis_of_Hereditary"><h2 id="_hsp_Differential_Diagnosis_of_Hereditary_">3. Differential Diagnosis of Hereditary Spastic Paraplegia</h2><p>The differential diagnosis includes the following:</p><ul><li class="half_rhythm"><div><b>Structural abnormalities</b> involving the brain or spinal cord (e.g., tethered cord syndrome and spinal cord compression)</div></li><li class="half_rhythm"><div><b>Vascular abnormalities</b> including arteriovenous abnormalities or fibrocartilaginous embolism</div></li><li class="half_rhythm"><div><b>Demyelinating disorders</b> including primary progressive multiple sclerosis or Devi's disease (neuromyelitis optica)</div></li><li class="half_rhythm"><div><b>Paraneoplastic myelopathies</b> including those associated with anti-GAD65 antibodies</div></li><li class="half_rhythm"><div><b>Other motor neuron disorders</b> such as slowly progressive <a href="/books/n/gene/als-overview/?report=reader">amyotrophic lateral sclerosis</a> (ALS) or primary lateral sclerosis (PLS)</div></li><li class="half_rhythm"><div><b>Leukodystrophies</b> such as steadily progressive multiple sclerosis, B<sub>12</sub> deficiency, <a href="/books/n/gene/krabbe/?report=reader">Krabbe disease</a>, <a href="/books/n/gene/mld/?report=reader">metachromatic leukodystrophy</a>, and <a href="/books/n/gene/pbd/?report=reader">adrenomyeloneuropathy</a></div></li><li class="half_rhythm"><div><b>Spinocerebellar ataxias (SCAs)</b> including Machado-Joseph disease (<a href="/books/n/gene/sca3/?report=reader">SCA 3</a>), <a href="/books/n/gene/friedreich/?report=reader">Friedreich ataxia</a>, <a href="/books/n/gene/arsacs/?report=reader">spastic ataxia of Charlevoix-Saguenay</a>, or other spastic ataxias. See <a href="/books/n/gene/ataxias/?report=reader">Hereditary Ataxias</a>.</div></li><li class="half_rhythm"><div><b>Diplegic form</b>
<b>of cerebral palsy (CP)</b> with corresponding MR imaging abnormalities. However, several individuals with presumed CP have had pathogenic variants in genes associated with HSP identified on molecular genetic testing associated with either an autosomal dominant or autosomal recessive inheritance [<a class="bibr" href="#hsp.REF.rainier.2006.445" rid="hsp.REF.rainier.2006.445">Rainier et al 2006</a>, <a class="bibr" href="#hsp.REF.hedera.2013.231" rid="hsp.REF.hedera.2013.231">Hedera 2013</a>].</div></li><li class="half_rhythm"><div><b>Infection</b> including human immunodeficiency virus (HIV/AIDs), tropical spastic paraplegia (also known as human T-cell leukemia virus 1 [HTLV1] -associated myelopathy), and neurosyphilis</div></li><li class="half_rhythm"><div><b>Metabolic disorders</b> (reviewed in <a class="bibr" href="#hsp.REF.hedera.2016.769" rid="hsp.REF.hedera.2016.769">Hedera [2016]</a>) including homocysteine remethylation defects (due to methylene tetrahydrofolate reductase [MTHFR] deficiency), <a href="/books/n/gene/cbl/?report=reader">cobalamin C disease</a>, <a href="/books/n/gene/ucd-overview/?report=reader">urea cycle defects</a>, <a href="/books/n/gene/biotin/?report=reader">biotinidase deficiency</a>, <a href="/books/n/gene/pku/?report=reader">phenylketonuria</a>, glycine encephalopathy, cerebral folate deficiency, homocarnosinosis, <a href="/books/n/gene/ctx/?report=reader">cerebrotendinous xanthomatosis</a>, <a href="/books/n/gene/apbd/?report=reader">adult polyglucosan body disease</a>, and nucleoside phosphorylase deficiency</div></li><li class="half_rhythm"><div><b>Nutritional disorders</b> (reviewed in <a class="bibr" href="#hsp.REF.hedera.2016.769" rid="hsp.REF.hedera.2016.769">Hedera [2016]</a>) including copper deficiency, vitamin B<sub>12</sub> and E deficiencies</div></li><li class="half_rhythm"><div><b>Early-onset dementias</b> including frontotemporal dementia-ALS (see <a href="/books/n/gene/als-overview/?report=reader">Amyotrophic Lateral Sclerosis Overview</a>) and familial Alzheimer disease caused by pathogenic variants in <i>PSEN1</i> (encoding presenilin-1), <i>PSEN2</i> (encoding presenilin-2), or APP (encoding amyloid precursor protein) (See <a href="/books/n/gene/alzheimer/?report=reader">Alzheimer Disease Overview</a>.)</div></li><li class="half_rhythm"><div><b>Dopa-responsive dystonia.</b> It is important to consider dopa-responsive dystonia in all individuals &#x02013; particularly children &#x02013; with progressive gait disturbance. See <a href="/books/n/gene/drd/?report=reader">GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia</a>, <a href="/books/n/gene/thdrd/?report=reader">Tyrosine Hydroxylase Deficiency</a>.</div></li></ul></div><div id="hsp.Evaluation_Strategies_to_Identify_th"><h2 id="_hsp_Evaluation_Strategies_to_Identify_th_">4. Evaluation Strategies to Identify the Genetic Cause of Hereditary Spastic Paraplegia in a Proband</h2><p>Establishing a specific genetic cause of hereditary spastic paraplegia (HSP):</p><ul><li class="half_rhythm"><div>Can aid in discussions of prognosis (which are beyond the scope of this <i>GeneReview</i>) and genetic counseling;</div></li><li class="half_rhythm"><div>Usually involves a medical history, physical examination, laboratory testing, family history, and genomic/genetic testing.</div></li></ul><p><b>Medical history and physical examination</b> is directed at identifying neurologic features associated with HSP as well as any additional features that could indicate the presence of a complicated HSP (see <a href="#hsp.Clinical_Characteristics_and_Recomme">Clinical Characteristics</a> and <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene">Tables 1</a>, <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_1/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene1">2</a>, <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_2/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene2">3</a>, and <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_3/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene3">4</a>).</p><p><b>Family history</b> includes a three-generation family history with attention to other relatives with possible HSP. Documentation of relevant findings in family members can be accomplished either through direct examination of those individuals or through review of their medical records including neuroimaging, neuropathology, neurologic examination, and results of molecular genetic testing. Autosomal dominant, autosomal recessive, and X-linked or maternal (mitochondrial) inheritance patterns have all been reported with HSP.</p><p><b>Exclusion of other disorders.</b> See <a href="#hsp.Differential_Diagnosis_of_Hereditary">Differential Diagnosis</a>.</p><p><b>Molecular genetic testing</b> approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, exome array). Gene-targeted testing requires the clinician to hypothesize which gene(s) are likely involved, whereas genomic testing does not.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Concurrent or serial single-gene testing</b> can be considered if clinical findings and/or family history indicate that involvement of a particular gene or small subset of genes is most likely (see <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene">Tables 1</a>, <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_1/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene1">2</a>, <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_2/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene2">3</a>, and <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_3/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene3">4</a>).</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A multigene panel</b> that includes some or all of the genes listed in <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene">Table 1</a> is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Comprehensive</b>
<b>genomic testing</b> (which does not require the clinician to determine which gene[s] are likely involved) may be considered. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible. <b>Exome array</b> (when clinically available) may be considered if exome sequencing is not diagnostic.</div><div class="half_rhythm">For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</div></li></ul></div><div id="hsp.Genetic_Counseling"><h2 id="_hsp_Genetic_Counseling_">5. Genetic Counseling</h2><p>
<i>Genetic counseling is the process of providing individuals and families with
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
make informed medical and personal decisions. The following section deals with genetic
risk assessment and the use of family history and genetic testing to clarify genetic
status for family members; it is not meant to address all personal, cultural, or
ethical issues that may arise or to substitute for consultation with a genetics
professional</i>. &#x02014;ED.</p><div id="hsp.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Hereditary spastic paraplegia (HSP) can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner or by maternal (mitochondrial) inheritance, depending on the genetic subtype in a family.</p><p>Several types of HSP (e.g., those associated with pathogenic variants in <i>ATL1</i>, <i>SPG7</i>, <i>ALDH18A1</i>, and possibly <i>SPG11</i>) may be inherited either as autosomal recessive or autosomal dominant disorders (see <a href="#hsp.Causes_of_Hereditary_Spastic_Paraple">Causes of Hereditary Spastic Paraplegia</a>).</p></div><div id="hsp.Risk_to_Family_Members"><h3>Risk to Family Members</h3><div id="hsp.Autosomal_Dominant_HSP"><h4>Autosomal Dominant HSP</h4><p>
<b>Parents of a proband</b>
</p><ul><li class="half_rhythm"><div>Most individuals diagnosed as having an autosomal dominant HSP have an affected parent.</div></li><li class="half_rhythm"><div>Occasionally, a proband with HSP may have the disorder as the result of a <i>de novo</i> pathogenic variant. The frequency of <i>de novo</i> variants causing autosomal dominant HSP is unknown.</div></li><li class="half_rhythm"><div>Recommendations for the evaluation of parents of a proband with an apparent <i>de novo</i> pathogenic variant include molecular genetic testing of both parents for the pathogenic variant identified in the proband.</div></li><li class="half_rhythm"><div>If the pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, possible explanations include a <i>de novo</i> pathogenic variant in the proband or germline mosaicism in a parent. Parental germline mosaicism has been reported in <i>SPAST</i>-related HSP (SPG4) [<a class="bibr" href="#hsp.REF.aulitzky.2014.352" rid="hsp.REF.aulitzky.2014.352">Aulitzky et al 2014</a>]. The incidence of parental germline mosaicism is probably very low, but no conclusive epidemiologic data are available.</div></li></ul><p>
<b>Sibs of a proband</b>
</p><ul><li class="half_rhythm"><div>The risk to the sibs of the proband depends on the genetic status of the proband's parents: if one of the proband's parents has a pathogenic variant, the risk to the sibs of inheriting the pathogenic variant is 50%.</div></li><li class="half_rhythm"><div>The age of onset and degree of disability are highly variable among members of the same family, in different families with the same pathogenic variant, or between genetic types of HSP.</div></li><li class="half_rhythm"><div>If the HSP-related pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the risk to sibs is slightly greater than that of the general population (though still &#x0003c;1%) because of the theoretic possibility of parental germline mosaicism.</div></li></ul><p><b>Offspring of a proband.</b> Each child of an individual with autosomal dominant HSP is at a 50% risk of inheriting the HSP-related pathogenic variant.</p><p><b>Other family members.</b> The risk to other family members depends on the status of the proband's parents: if a parent is affected, the parent's family members may be at risk.</p></div><div id="hsp.Autosomal_Recessive_HSP"><h4>Autosomal Recessive HSP</h4><p>
<b>Parents of a proband</b>
</p><ul><li class="half_rhythm"><div>The parents of an affected individual are obligate heterozygotes (i.e., carriers of one HSP-related pathogenic variant).</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are typically asymptomatic. The only known exception to this rule is <i>SPG7</i>, where an apparently dominant inheritance was suggested for otherwise autosomal recessive HSP [<a class="bibr" href="#hsp.REF.mcdermott.2001.467" rid="hsp.REF.mcdermott.2001.467">McDermott et al 2001</a>].</div></li></ul><p>
<b>Sibs of a proband</b>
</p><ul><li class="half_rhythm"><div>At conception, each sib has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Heterozygotes are typically asymptomatic if the pattern of inheritance is consistent with autosomal recessive mode and affected individuals harbor biallelic pathogenic variants.</div></li></ul><p><b>Offspring of a proband.</b> The offspring of an individual with autosomal recessive HSP are obligate heterozygotes (carriers) for an HSP-related pathogenic variant.</p><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier of an HSP-related pathogenic variant.</p></div><div id="hsp.XLinked_HSP"><h4>X-Linked HSP</h4><p>
<b>Parents of a male proband</b>
</p><ul><li class="half_rhythm"><div>The father of an affected male will not have the disorder nor will he be hemizygous for the HSP-related pathogenic variant; therefore, he does not require further evaluation/testing.</div></li><li class="half_rhythm"><div>In a family with more than one individual with X-linked HSP, the mother of an affected male is an obligate carrier of the HSP-related pathogenic variant. If a woman has more than one affected child and if the HSP-related pathogenic variant cannot be detected in her leukocyte DNA, she most likely has germline mosaicism (maternal germline and somatic mosaicism in <i>L1CAM</i>-related HSP [SPG1] has been reported [<a class="bibr" href="#hsp.REF.du.1998.200" rid="hsp.REF.du.1998.200">Du et al 1998</a>, <a class="bibr" href="#hsp.REF.vits.1998.s284" rid="hsp.REF.vits.1998.s284">Vits et al 1998</a>]).</div></li><li class="half_rhythm"><div>If a male is the only affected family member (i.e., a simplex case), the mother may be a heterozygote or the affected male may have a <i>de novo</i> HSP-related pathogenic variant, in which case the mother is not a heterozygote.</div></li></ul><p>
<b>Parents of a female proband</b>
</p><ul><li class="half_rhythm"><div>A female proband may have inherited the HSP-related pathogenic variant from either her mother or her father, or the pathogenic variant may be <i>de novo</i>.</div></li><li class="half_rhythm"><div>Detailed evaluation of the parents and review of the extended family history may help distinguish probands with a <i>de novo</i> pathogenic variant from those with an inherited pathogenic variant. Molecular genetic testing of the mother (and possibly the father, or subsequently the father) can determine if the pathogenic variant was inherited.</div></li></ul><p>
<b>Sibs of a male proband</b>
</p><ul><li class="half_rhythm"><div>The risk to sibs depends on the genetic status of the mother.</div><ul><li class="half_rhythm"><div>If the mother of the proband with X-linked HSP has an HSP-related pathogenic variant, the chance of transmitting it in each pregnancy is 50%. Males who inherit the variant will be affected; females who inherit the variant will be heterozygotes and may have a range of clinical manifestations (see <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_2/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene2">Table 3</a>).</div></li><li class="half_rhythm"><div>If the proband represents a simplex case (i.e., a single occurrence in a family) and if the HSP-related pathogenic variant cannot be detected in the leukocyte DNA of the mother, the risk to sibs is slightly greater than that of the general population (though still &#x0003c;1%) because of the theoretic possibility of maternal germline mosaicism.</div></li></ul></li><li class="half_rhythm"><div>The age of onset, penetrance, and degree of disability are not predictable in members of the same family, in different families with the same pathogenic variant, or between genetic types of HSP.</div></li></ul><p>
<b>Sibs of a female proband</b>
</p><ul><li class="half_rhythm"><div>The risk to sibs depends on the genetic status of the parents.</div><ul><li class="half_rhythm"><div>If the mother of the proband has an HSP-related pathogenic variant, the chance of transmitting it in each pregnancy is 50%. Males who inherit the variant will be affected; females who inherit the variant will be heterozygotes and may have a range of clinical manifestations (see <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_2/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene2">Table 3</a>).</div></li><li class="half_rhythm"><div>If the father of the proband has an HSP-related pathogenic variant, he will transmit it to all of his daughters and none of his sons.</div></li></ul></li><li class="half_rhythm"><div>If the proband represents a simplex case (i.e., a single occurrence in a family) and if the HSP-related pathogenic variant cannot be detected in the leukocyte DNA of either parent, the risk to sibs is slightly greater than that of the general population (though still &#x0003c;1%) because of the possibility of parental germline mosaicism.</div></li><li class="half_rhythm"><div>The age of onset, penetrance, and degree of disability are not predictable in members of the same family, in different families with the same pathogenic variant, or between genetic types of HSP.</div></li></ul><p><b>Offspring of a male proband.</b> Affected males transmit the HSP-related pathogenic variant to:</p><ul><li class="half_rhythm"><div>All of their daughters, who will be heterozygotes and may have a range of clinical manifestations (see <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_2/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene2">Table 3</a>);</div></li><li class="half_rhythm"><div>None of their sons.</div></li></ul><p><b>Offspring of a female proband.</b> Women with an HSP-related pathogenic variant have a 50% chance of transmitting the pathogenic variant to each child:</p><ul><li class="half_rhythm"><div>Males who inherit the pathogenic variant will be affected.</div></li><li class="half_rhythm"><div>Females who inherit the variant will be heterozygotes and may have a range of clinical manifestations (see <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_2/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene2">Table 3</a>). This is best documented for <i>SPG2</i>, where female heterozygotes may show a mild paraparesis with late onset of the disease [<a class="bibr" href="#hsp.REF.sivakumar.1999.680" rid="hsp.REF.sivakumar.1999.680">Sivakumar et al 1999</a>].</div></li></ul><p><b>Other family members.</b> The risk to other family members depends on the status of the proband's parents: if a parent has the HSP-related pathogenic variant, the parent's family members may be at risk.</p><p><b>Heterozygote (carrier) detection.</b> Molecular genetic testing of at-risk female relatives to determine their genetic status is most informative if the pathogenic variant has been identified in the proband.</p><p>Note: (1) Females who are heterozygous for X-linked HSP may have a range of clinical manifestations (see <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_2/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene2">Table 3</a>). (2) Identification of female heterozygotes requires either (a) prior identification of the HSP-related pathogenic variant in the family or, (b) if an affected male is not available for testing, molecular genetic testing first by sequence analysis, and if no pathogenic variant is identified, by gene-targeted deletion/duplication analysis.</p></div><div id="hsp.Maternal_Mitochondrial_Inheritance"><h4>Maternal (Mitochondrial) Inheritance</h4><p>
<b>Parents of a proband</b>
</p><ul><li class="half_rhythm"><div>The father of a proband is not at risk of having the <i>MT-ATP6</i> pathogenic variant.</div></li><li class="half_rhythm"><div>The mother of a proband (usually) has the <i>MT-ATP6</i> pathogenic variant and may or may not have symptoms.</div></li><li class="half_rhythm"><div>Alternatively, the proband may have a <i>de novo</i> (somatic) mitochondrial pathogenic variant.</div></li></ul><p>
<b>Sibs of a proband</b>
</p><ul><li class="half_rhythm"><div>The risk to the sibs depends on the genetic status of the mother.</div></li><li class="half_rhythm"><div>If the mother has the <i>MT-ATP6</i> pathogenic variant, all sibs of a proband will inherit the <i>MT-ATP6</i> pathogenic variant and may or may not have symptoms.</div></li></ul><p>
<b>Offspring of a proband</b>
</p><ul><li class="half_rhythm"><div>All offspring of females with a mtDNA pathogenic variant will inherit the pathogenic variant.</div></li><li class="half_rhythm"><div>Offspring of males with a mtDNA pathogenic variant are not at risk of inheriting the pathogenic variant.</div></li></ul><p><b>Other family members.</b> The risk to other family members depends on the genetic status of the proband's mother. If the mother has an <i>MT-ATP6</i> pathogenic variant, her sibs and mother are also at risk.</p></div></div><div id="hsp.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>Caution must be exercised when counseling an individual who has all the signs and symptoms of HSP but no similarly affected relatives. Such individuals may be diagnosed as having primary lateral sclerosis (PLS). While such individuals with no known family history of HSP may have autosomal recessive HSP (and thus low risk of transmitting the disorder to offspring), it is also possible that they have X-linked HSP, autosomal dominant HSP with reduced penetrance, a <i>de novo</i> pathogenic variant, a mtDNA pathogenic variant, mistaken paternity, or an environmentally acquired disorder.</p><p>
<b>Family planning</b>
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy. Similarly, decisions about testing to determine the genetic status of at-risk asymptomatic family members are best made before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including general discussion of potential risks to offspring and reproductive options) to young adults who are affected, carriers, or at risk of being affected or a carrier; however, it is not possible to make specific predictions about the potential severity of disease in offspring.</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see <a class="bibr" href="#hsp.REF.huang.2022.389" rid="hsp.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="hsp.Prenatal_Testing_and_Preimplantation"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for hereditary spastic paraplegia are possible.</p></div></div><div id="hsp.Resources"><h2 id="_hsp_Resources_">Resources</h2><p>
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
support organizations and/or registries for the benefit of individuals with this disorder
and their families. GeneReviews is not responsible for the information provided by other
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
<ul><li class="half_rhythm"><div>
<b>EURO HSP</b>
</div><div>
<a href="https://www.eurohsp.eu" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">eurohsp.eu</a>
</div></li><li class="half_rhythm"><div>
<b>HSP Research Foundation</b>
</div><div>Australia</div><div><b>Email:</b> inquiries@hspersunite.org.au</div><div>
<a href="https://www.hspersunite.org.au/" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">hspersunite.org.au</a>
</div></li><li class="half_rhythm"><div>
<b>National Institute of Neurological Disorders and Stroke (NINDS)</b>
</div><div>
<a href="https://www.ninds.nih.gov/Disorders/All-Disorders/Hereditary-Spastic-Paraplegia-Information-Page" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">Hereditary Spastic Paraplegia</a>
</div></li><li class="half_rhythm"><div>
<b>National Organization for Rare Disorders (NORD)</b>
</div><div>
<a href="https://rarediseases.org/rare-diseases/hereditary-spastic-paraplegia/" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">Hereditary Spastic Paraplegia</a>
</div></li><li class="half_rhythm"><div>
<b>Spastic Paraplegia Foundation, Inc.</b>
</div><div><b>Phone:</b> 877-773-4483</div><div><b>Email:</b> information@sp-foundation.org</div><div>
<a href="http://sp-foundation.org" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">sp-foundation.org</a>
</div></li><li class="half_rhythm"><div>
<b>Tom Wahlig Foundation</b>
</div><div>Tom Wahlig Stiftung</div><div>Germany</div><div>
<a href="https://www.hsp-info.de/en/foundation.htm" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">hsp-info.de/en/foundation.htm</a>
</div></li><li class="half_rhythm"><div>
<b>A.I. Vi.P.S.</b>
</div><div>Associazione Italiana Vivere la Paraparesi Spastica</div><div>Italy</div><div><b>Phone:</b> 39 392 9825622</div><div><b>Email:</b> info@aivips.it</div><div>
<a href="https://www.aivips.it/" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">aivips.it</a>
</div></li></ul>
</div><div id="hsp.Chapter_Notes"><h2 id="_hsp_Chapter_Notes_">Chapter Notes</h2><div id="hsp.Author_History"><h3>Author History</h3><p>John K Fink, MD; University of Michigan (2000-2018)<br />Peter Hedera, MD, PhD, FACMG (2018-present)</p></div><div id="hsp.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>11 February 2021 (aa/ha/ph) Revision: added AD SPG30 and associated references; updated SPG1/MASA syndrome terminology information</div></li><li class="half_rhythm"><div>27 September 2018 (ha) Comprehensive update posted live</div></li><li class="half_rhythm"><div>6 February 2014 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>11 July 2007 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>22 September 2003 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>15 August 2000 (me) Overview posted live</div></li><li class="half_rhythm"><div>21 March 2000 (jf) Original submission</div></li></ul></div></div><div id="hsp.References"><h2 id="_hsp_References_">References</h2><div id="hsp.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="hsp.REF.abou_jamra.2011.788">Abou Jamra
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[<a href="https://pubmed.ncbi.nlm.nih.gov/7782849" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 7782849</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hsp.REF.y_ld_r_m.2011.1886">Y&#x00131;ld&#x00131;r&#x00131;m
Y, Orhan
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[<a href="https://pubmed.ncbi.nlm.nih.gov/21330303" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 21330303</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hsp.REF.zhao.2001.326">Zhao
X, Alvarado
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[<a href="https://pubmed.ncbi.nlm.nih.gov/11685207" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 11685207</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hsp.REF.z_chner.2006.365">Z&#x000fc;chner
S, Wang
G, Tran-Viet
KN, Nance
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JM, Ashley-Koch
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MA. Mutations in the novel mitochondrial protein REEP1 cause hereditary spastic paraplegia type 31.
Am J Hum Genet
2006;79:365&#x02013;9.
[<a href="/pmc/articles/PMC1559498/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC1559498</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16826527" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 16826527</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1509_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Peter Hedera</span>, MD, PhD, FACMG<div class="affiliation small">Department of Neurology<br />Vanderbilt University<br />Nashville, Tennessee<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.tlibrednav@aredeh.retep" class="oemail">ude.tlibrednav@aredeh.retep</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">August 15, 2000</span>; Last Revision: <span itemprop="dateModified">February 11, 2021</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> &#x000a9; 1993-2025, University of Washington, Seattle. GeneReviews is
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&amp;targetsite=external&amp;targetcat=link&amp;targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Hedera P. Hereditary Spastic Paraplegia Overview. 2000 Aug 15 [Updated 2021 Feb 11]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews&#x000ae; [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/hsan2/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/tfap/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobhspThereditaryspasticparaplegiagene"><div id="hsp.T.hereditary_spastic_paraplegia_gene" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Hereditary Spastic Paraplegia: Genes and Distinguishing Clinical Features &#x02013; Autosomal Dominant Inheritance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hsp.T.hereditary_spastic_paraplegia_gene_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" rowspan="2" scope="rowgroup" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene&#x000a0;<sup>1</sup></th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" style="text-align:left;vertical-align:middle;">HSP Designation</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" style="text-align:left;vertical-align:middle;">Type of HSP</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" style="text-align:left;vertical-align:middle;">Onset</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" style="text-align:left;vertical-align:middle;">Distinguishing Clinical Features</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" style="text-align:left;vertical-align:middle;">Other</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">References</th></tr><tr><th headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7" id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;"><i>GeneReview</i> or OMIM Entry</th><th headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7" id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Citation</th></tr></thead><tbody><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ADAR</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not assigned</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Abnormal pattern of interferon expression determined by reverse transcription PCR assay</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reported in a single Hispanic individual</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.crow.2014.386" rid="hsp.REF.crow.2014.386">Crow et al [2014]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ALDH18A1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG9A</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adolescence to adulthood (1 subject w/infantile onset)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cataracts</div></li><li class="half_rhythm"><div>Gastroesophageal reflux</div></li><li class="half_rhythm"><div>Motor neuronopathy</div></li></ul>
Variably present:
<ul><li class="half_rhythm"><div>Dysarthria</div></li><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Cognitive impairment</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Rare</div></li><li class="half_rhythm"><div>Allelic w/AR HSP (SPG9B)</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/601162" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">601162</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.coutelier.2015.2191" rid="hsp.REF.coutelier.2015.2191">Coutelier et al [2015]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ATAD3A</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not assigned</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early onset</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Amyotrophy</div></li><li class="half_rhythm"><div>Hyperkinetic movements</div></li><li class="half_rhythm"><div>May be confused w/hyperkinetic cerebral palsy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.cooper.2017.1432" rid="hsp.REF.cooper.2017.1432">Cooper et al [2017]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ATL1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG3A</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infantile to childhood (rarely adult onset)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Progression may be minimal w/static course.</div></li><li class="half_rhythm"><div>May present as spastic diplegic cerebral palsy</div></li><li class="half_rhythm"><div>Complicated phenotype w/peripheral neuropathy or autonomic failure reported</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>80% of early-onset AD HSP</div></li><li class="half_rhythm"><div>10%-15% of all AD HSP</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/spg3a/?report=reader">Spastic Paraplegia 3A</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.zhao.2001.326" rid="hsp.REF.zhao.2001.326">Zhao et al [2001]</a>, <a class="bibr" href="#hsp.REF.namekawa.2006.112" rid="hsp.REF.namekawa.2006.112">Namekawa et al [2006]</a>, <a class="bibr" href="#hsp.REF.rainier.2006.445" rid="hsp.REF.rainier.2006.445">Rainier et al [2006]</a>, <a class="bibr" href="#hsp.REF.ivanova.2007.706" rid="hsp.REF.ivanova.2007.706">Ivanova et al [2007]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>BICD2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not assigned</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood or adult</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Infantile onset assoc w/SMA w/variable upper motor signs &#x00026; contractures</div></li><li class="half_rhythm"><div>Adult onset assoc w/mild amyotrophy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.oates.2013.965" rid="hsp.REF.oates.2013.965">Oates et al [2013]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>BSCL2</i>&#x000a0;<sup>2</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG17</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Distal amyotrophy affecting hands &#x00026; feet</div></li><li class="half_rhythm"><div>Motor neuropathy</div></li><li class="half_rhythm"><div>Can be indistinguishable from ALS</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/spg17/?report=reader"><i>BSCL2</i>-Related Neurologic Disorders/ Seipinopathy</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.windpassinger.2004.271" rid="hsp.REF.windpassinger.2004.271">Windpassinger et al [2004]</a>, <a class="bibr" href="#hsp.REF.musacchio.2017.11" rid="hsp.REF.musacchio.2017.11">Musacchio et al [2017]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>CPT1C</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG73</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Foot deformity may be present.</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Single family</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/616282" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">616282</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.rinaldi.2015.561" rid="hsp.REF.rinaldi.2015.561">Rinaldi et al [2015]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>DNM2</i>
<sup>3</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not assigned</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Before age 20 yrs</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Axonal polyneuropathy may be present.</div></li><li class="half_rhythm"><div>Mild distal amyotrophy in feet</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Single family</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.sambuughin.2015.223" rid="hsp.REF.sambuughin.2015.223">Sambuughin et al [2015]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ERLIN2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG18&#x000a0;<sup>4</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Juvenile to adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Single family</div></li><li class="half_rhythm"><div>Most pathogenic variants assoc w/AR HSP (See <a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_1/?report=objectonly" target="object" rid-ob="figobhspThereditaryspasticparaplegiagene1">Table 2</a>.)</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.rydning.2018.943" rid="hsp.REF.rydning.2018.943">Rydning et al [2018]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>HSPD1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG13</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild distal amyotrophy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/605280" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">605280</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.hansen.2002.1328" rid="hsp.REF.hansen.2002.1328">Hansen et al [2002]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>KIF1A</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG30</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated (for AD inheritance)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Juvenile to adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Some individuals have mild ID.</div></li><li class="half_rhythm"><div>Optic nerve atrophy, epilepsy can be rarely seen in AD SPG30.</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5%-6% of all AD HSP</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/610357" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">610357</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.roda.2017.821" rid="hsp.REF.roda.2017.821">Roda et al [2017]</a>, <a class="bibr" href="#hsp.REF.pennings.2020.40" rid="hsp.REF.pennings.2020.40">Pennings et al [2020]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>KIF5A</i>
<sup>4</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG10</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Juvenile or adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Polyneuropathy</div></li><li class="half_rhythm"><div>Pes cavus</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>1%-2% of all AD HSP</div></li><li class="half_rhythm"><div>5%-8% of all complicated AD HSP</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/604187" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">604187</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.reid.2002.1189" rid="hsp.REF.reid.2002.1189">Reid et al [2002]</a>, <a class="bibr" href="#hsp.REF.blair.2006.47" rid="hsp.REF.blair.2006.47">Blair et al [2006]</a>, <a class="bibr" href="#hsp.REF.liu.2014.612" rid="hsp.REF.liu.2014.612">Liu et al [2014]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>NIPA1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG6</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adulthood (infantile onset rare)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe weakness &#x00026; spasticity</div></li><li class="half_rhythm"><div>Rapidly progressive</div></li><li class="half_rhythm"><div>Rarely, complicated by epilepsy or variable peripheral neuropathy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare (~1% of AD HSP)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/600363" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">600363</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.rainier.2003.967" rid="hsp.REF.rainier.2003.967">Rainier et al [2003]</a>, <a class="bibr" href="#hsp.REF.du.2011.480" rid="hsp.REF.du.2011.480">Du et al [2011]</a>, <a class="bibr" href="#hsp.REF.svenstrup.2011.1197" rid="hsp.REF.svenstrup.2011.1197">Svenstrup et al [2011]</a>, <a class="bibr" href="#hsp.REF.hedera.2013.231" rid="hsp.REF.hedera.2013.231">Hedera [2013]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ATP2B4</i> (<i>PMCA4</i>)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not assigned</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Single family</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.li.2014.e104790" rid="hsp.REF.li.2014.e104790">Li et al [2014]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>REEP1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG31</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Variable from 2nd to 7th decades</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild amyotrophy variably present.</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common, 4%-6% of all AD HSP</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/610250" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">610250</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.z_chner.2006.365" rid="hsp.REF.z_chner.2006.365">Z&#x000fc;chner et al [2006]</a>, <a class="bibr" href="#hsp.REF.hewamadduma.2009.105" rid="hsp.REF.hewamadduma.2009.105">Hewamadduma et al [2009]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>REEP2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG72</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Very early, average age 4 yrs</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Musculoskeletal problems</div></li><li class="half_rhythm"><div>Mild postural tremor</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Rare</div></li><li class="half_rhythm"><div>Inheritance can be dominant or recessive</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/615625" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">615625</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.esteves.2014.268" rid="hsp.REF.esteves.2014.268">Esteves et al [2014]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>RTN2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG12</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Before age 20 yrs</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5% of early-onset AD HSP but overall rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/604805" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">604805</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.montenegro.2012.538" rid="hsp.REF.montenegro.2012.538">Montenegro et al [2012]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>SLC33A1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG42</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Slowly progressive</div></li><li class="half_rhythm"><div>Mild pes cavus</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Single family known</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/612539" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">612539</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.lin.2008.752" rid="hsp.REF.lin.2008.752">Lin et al [2008]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>SPAST</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG4</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Variable from infancy to 7th decade</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cognitive decline &#x00026; dementia common</div></li><li class="half_rhythm"><div>Distal amyotrophy variably present</div></li><li class="half_rhythm"><div>Complicated phenotype w/ataxia variably present</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">40% of AD HSP</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/spg4/?report=reader">Spastic Paraplegia 4</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.hazan.1999.296" rid="hsp.REF.hazan.1999.296">Hazan et al [1999]</a>, <a class="bibr" href="#hsp.REF.fonknechten.2000.637" rid="hsp.REF.fonknechten.2000.637">Fonknechten et al [2000]</a>, <a class="bibr" href="#hsp.REF.nielsen.2004.817" rid="hsp.REF.nielsen.2004.817">Nielsen et al [2004]</a>, <a class="bibr" href="#hsp.REF.murphy.2009.378" rid="hsp.REF.murphy.2009.378">Murphy et al [2009]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>SPG7</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG7</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated or complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Juvenile or adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Dysarthria</div></li><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Optic atrophy</div></li><li class="half_rhythm"><div>Supranuclear palsy</div></li><li class="half_rhythm"><div>Mitochondrial abnormalities on skeletal muscle biopsy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD inheritance suggested for some pathogenic variants, but overall this is rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/spg7/?report=reader">Spastic Paraplegia 7</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.mcdermott.2001.467" rid="hsp.REF.mcdermott.2001.467">McDermott et al [2001]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>WASHC5</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG8</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adulthood (rare infantile onset reported)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe motor deficit in some individuals</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare (~1% of AD HSP)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/spg8/?report=reader">Spastic Paraplegia 8</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.hedera.1999.44" rid="hsp.REF.hedera.1999.44">Hedera et al [1999]</a>, <a class="bibr" href="#hsp.REF.valdmanis.2007.152" rid="hsp.REF.valdmanis.2007.152">Valdmanis et al [2007]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TUBB4A</i>&#x000a0;<sup>5</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not assigned</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Juvenile</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cerebellar ataxia</div></li><li class="half_rhythm"><div>MRI evidence of hypomyelination</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.kancheva.2015.854" rid="hsp.REF.kancheva.2015.854">Kancheva et al [2015]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ZFYVE27</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG33</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild pes cavus</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Single family known</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/610244" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">610244</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.mannan.2006.351" rid="hsp.REF.mannan.2006.351">Mannan et al [2006]</a>
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; ALS = amyotrophic lateral sclerosis; CMT = Charcot-Marie-Tooth neuropathy; DI-CMT = dominant intermediate Charcot-Marie-Tooth neuropathy; HMN = hereditary motor neuropathy; HSP = hereditary spastic paraplegia; ID = intelectual disability; SMA = spinal muscular atrophy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="hsp.TF.1.1"><p class="no_margin">Genes are listed alphabetically.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="hsp.TF.1.2"><p class="no_margin">Allelic with distal hereditary motor neuropathy type V (dHMN-V) and variants of Charcot-Marie-Tooth disease type 2</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="hsp.TF.1.3"><p class="no_margin">Allelic with CMT2M; DI-CMTB, centronuclear myopathy; &#x00026; lethal congenital contractures syndrome type 5</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="hsp.TF.1.4"><p class="no_margin">Allelic with Charcot-Marie-Tooth disease axonal CMT2A and ALS25 (susceptibility to ALS)</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="hsp.TF.1.5"><p class="no_margin">Allelic with hypomyelinating leukodystrophy type 6 and autosomal dominant dystonia type 4</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhspThereditaryspasticparaplegiagene1"><div id="hsp.T.hereditary_spastic_paraplegia_gene_1" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Hereditary Spastic Paraplegia: Genes and Distinguishing Clinical Features &#x02013; Autosomal Recessive Inheritance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hsp.T.hereditary_spastic_paraplegia_gene_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" rowspan="2" scope="rowgroup" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene&#x000a0;<sup>1</sup></th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" style="text-align:left;vertical-align:middle;">HSP Designation</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" style="text-align:left;vertical-align:middle;">Type of HSP</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" style="text-align:left;vertical-align:middle;">Onset</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" style="text-align:left;vertical-align:middle;">Distinguishing Clinical Features</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" style="text-align:left;vertical-align:middle;">Other</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">References</th></tr><tr><th headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7" id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;"><i>GeneReview</i><br />or OMIM Entry</th><th headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7" id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Citation</th></tr></thead><tbody><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SPG21</i><br />(<i>ACP33</i>)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG21</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Adult-onset dementia &#x00026; parkinsonism</div></li><li class="half_rhythm"><div>Polyneuropathy</div></li><li class="half_rhythm"><div>Akinetic mutism seen in advanced cases</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Rare, first described in Old Order Amish population (later identified in various ethnic groups)</div></li><li class="half_rhythm"><div>Also known as Mast syndrome</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/248900" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">248900</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.cross.1967a.1" rid="hsp.REF.cross.1967a.1">Cross &#x00026; McKusick [1967a]</a>, <a class="bibr" href="#hsp.REF.simpson.2003.1147" rid="hsp.REF.simpson.2003.1147">Simpson et al [2003]</a>, <a class="bibr" href="#hsp.REF.ishiura.2014.163" rid="hsp.REF.ishiura.2014.163">Ishiura et al [2014]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ALDH18A1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG9B</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adolescence to adulthood (one subject w/infantile onset)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Cataracts</div></li><li class="half_rhythm"><div>Gastroesophageal reflux</div></li><li class="half_rhythm"><div>Motor neuronopathy</div></li></ul>
Variably present:
<ul><li class="half_rhythm"><div>Dysarthria</div></li><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Cognitive impairment</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Rare</div></li><li class="half_rhythm"><div>Allelic w/AD HSP (SPG9A)</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/616586" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">616586</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.coutelier.2015.2191" rid="hsp.REF.coutelier.2015.2191">Coutelier et al [2015]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ALDH3A2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not assigned</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Congenital ichthyosis</div></li><li class="half_rhythm"><div>Macular dystrophy</div></li><li class="half_rhythm"><div>Leukodystrophy</div></li><li class="half_rhythm"><div>Seizures in ~40% of affected persons</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Rare</div></li><li class="half_rhythm"><div>Most common in people of Swedish ancestry</div></li><li class="half_rhythm"><div>Known as Sj&#x000f6;gren-Larsson syndrome</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.rizzo.1999.1547" rid="hsp.REF.rizzo.1999.1547">Rizzo et al [1999]</a>, <a class="bibr" href="#hsp.REF.gordon.2007.152" rid="hsp.REF.gordon.2007.152">Gordon [2007]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>AMPD2</i>&#x000a0;<sup>2</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG63</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Short stature</div></li><li class="half_rhythm"><div>Thin corpus callosum</div></li><li class="half_rhythm"><div>White matter changes</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/615686" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">615686</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.novarino.2014.506" rid="hsp.REF.novarino.2014.506">Novarino et al [2014]</a>, <a class="bibr" href="#hsp.REF.kort_m.2018.695" rid="hsp.REF.kort_m.2018.695">Kort&#x000fc;m et al [2018]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>AP4B1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG47</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe ID</div></li><li class="half_rhythm"><div>Facial dysmorphism</div></li><li class="half_rhythm"><div>Seizures</div></li><li class="half_rhythm"><div>Stereotypic laughter w/tongue protrusion</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/614066" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">614066</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.abou_jamra.2011.788" rid="hsp.REF.abou_jamra.2011.788">Abou Jamra et al [2011]</a>, <a class="bibr" href="#hsp.REF.bauer.2012.73" rid="hsp.REF.bauer.2012.73">Bauer et al [2012]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>AP4E1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG51</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe ID</div></li><li class="half_rhythm"><div>Facial dysmorphism</div></li><li class="half_rhythm"><div>Seizures</div></li><li class="half_rhythm"><div>Stereotypic laughter w/tongue protrusion</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/613744" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">613744</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.abou_jamra.2011.788" rid="hsp.REF.abou_jamra.2011.788">Abou Jamra et al [2011]</a>, <a class="bibr" href="#hsp.REF.morenodeluca.2011.141" rid="hsp.REF.morenodeluca.2011.141">Moreno-De-Luca et al [2011]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>AP4M1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG50</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe ID</div></li><li class="half_rhythm"><div>Facial dysmorphism</div></li><li class="half_rhythm"><div>Seizures</div></li><li class="half_rhythm"><div>Stereotypic laughter w/tongue protrusion</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/612936" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">612936</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.verkerk.2009.40" rid="hsp.REF.verkerk.2009.40">Verkerk et al [2009]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>AP4S1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG52</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe ID</div></li><li class="half_rhythm"><div>Facial dysmorphism</div></li><li class="half_rhythm"><div>Seizures</div></li><li class="half_rhythm"><div>Stereotypic laughter w/tongue protrusion</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/614067" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">614067</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.abou_jamra.2011.788" rid="hsp.REF.abou_jamra.2011.788">Abou Jamra et al [2011]</a>, <a class="bibr" href="#hsp.REF.hardies.2015.2218" rid="hsp.REF.hardies.2015.2218">Hardies et al [2015]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>AP5Z1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG48</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically adulthood; rarely infancy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Urinary incontinence</div></li><li class="half_rhythm"><div>Parkinsonism</div></li><li class="half_rhythm"><div>Dystonia</div></li><li class="half_rhythm"><div>Thin corpus callosum</div></li><li class="half_rhythm"><div>Leukodystrophy</div></li><li class="half_rhythm"><div>Severe DD in infantile onset</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Single family</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/613647" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">613647</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.s_abicki.2010.e1000408" rid="hsp.REF.s_abicki.2010.e1000408">S&#x00142;abicki et al [2010]</a>, <a class="bibr" href="#hsp.REF.pensato.2014.1907" rid="hsp.REF.pensato.2014.1907">Pensato et al [2014]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ATL1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG3A</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infantile to childhood (rarely adult onset)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Progression may be minimal w/static course</div></li><li class="half_rhythm"><div>May present as spastic diplegic cerebral palsy</div></li><li class="half_rhythm"><div>Complicated phenotype w/peripheral neuropathy or autonomic failure reported</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR inheritance is very rare.</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/spg3a/?report=reader">Spastic Paraplegia 3A</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.khan.2014.1180" rid="hsp.REF.khan.2014.1180">Khan et al [2014]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>B4GALNT1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG26</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Juvenile</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Amyotrophy</div></li><li class="half_rhythm"><div>Dysarthria</div></li><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Dystonia</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/609195" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">609195</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.boukhris.2013.118" rid="hsp.REF.boukhris.2013.118">Boukhris et al [2013]</a>, <a class="bibr" href="#hsp.REF.harlalka.2013.3618" rid="hsp.REF.harlalka.2013.3618">Harlalka et al [2013]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>BICD2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not assigned</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Amyotrophy</div></li><li class="half_rhythm"><div>Contractures</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.oates.2013.965" rid="hsp.REF.oates.2013.965">Oates et al [2013]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>MTRFR</i> (<i>C12orf65</i>)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG55</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Visual loss</div></li><li class="half_rhythm"><div>Polyneuropathy</div></li><li class="half_rhythm"><div>Arthrogryposis</div></li><li class="half_rhythm"><div>Signs of mitochondrial encephalomyopathy, some classified as Leigh's syndrome</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/615035" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">615035</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.shimazaki.2012.777" rid="hsp.REF.shimazaki.2012.777">Shimazaki et al [2012]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>C19orf12</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG43</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Amyotrophy</div></li><li class="half_rhythm"><div>Dysarthria</div></li><li class="half_rhythm"><div>Multiple contractures</div></li><li class="half_rhythm"><div>Neurodegeneration w/brain iron accumulation in some</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/615043" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">615043</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.landour_.2013.1357" rid="hsp.REF.landour_.2013.1357">Landour&#x000e9; et al [2013]</a>, <a class="bibr" href="#hsp.REF.schubert.2016.53" rid="hsp.REF.schubert.2016.53">Schubert et al [2016]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>CYP2U1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG56</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe DD</div></li><li class="half_rhythm"><div>Dystonia</div></li><li class="half_rhythm"><div>Polyneuropathy</div></li><li class="half_rhythm"><div>Calcification of basal ganglia</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/615030" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">615030</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.tesson.2012.1051" rid="hsp.REF.tesson.2012.1051">Tesson et al [2012]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>CYP7B1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG5A</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated or complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Juvenile to early adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Polyneuropathy</div></li><li class="half_rhythm"><div>Extrapyramidal signs</div></li><li class="half_rhythm"><div>MRI signs of leukodystrophy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG5A was diagnosed in 9 of 172 families w/histories consistent w/AR inheritance of HSP.&#x000a0;<sup>3</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/270800" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">270800</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.tsaousidou.2008.510" rid="hsp.REF.tsaousidou.2008.510">Tsaousidou et al [2008]</a>, <a class="bibr" href="#hsp.REF.goizet.2009.1589" rid="hsp.REF.goizet.2009.1589">Goizet et al [2009]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>DDHD1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG28</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Scoliosis</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/609340" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">609340</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.tesson.2012.1051" rid="hsp.REF.tesson.2012.1051">Tesson et al [2012]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>DDHD2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG54</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe DD</div></li><li class="half_rhythm"><div>Optic atrophy</div></li><li class="half_rhythm"><div>Thin corpus callosum</div></li><li class="half_rhythm"><div>Leukodystrophy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/615033" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">615033</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.schuurshoeijmakers.2012.1073" rid="hsp.REF.schuurshoeijmakers.2012.1073">Schuurs-Hoeijmakers et al [2012]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ENTPD1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG64</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Mild cognitive disability</div></li><li class="half_rhythm"><div>Behavioral disturbances</div></li><li class="half_rhythm"><div>White matter changes</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/entpd1-ndd/?report=reader"><i>ENTPD1</i>-Related Neurodevelopmental Disorder</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.novarino.2014.506" rid="hsp.REF.novarino.2014.506">Novarino et al [2014]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ERLIN1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG62</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Amyotrophy</div></li><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Phenotype consistent w/juvenile onset of ALS reported</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/615681" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">615681</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.novarino.2014.506" rid="hsp.REF.novarino.2014.506">Novarino et al [2014]</a>, <a class="bibr" href="#hsp.REF.tunca.2018.745" rid="hsp.REF.tunca.2018.745">Tunca et al [2018]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ERLIN2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG18</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated (rarely pure AR HSP reported)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Seizures</div></li><li class="half_rhythm"><div>Contractures</div></li><li class="half_rhythm"><div>Juvenile primary lateral sclerosis phenotype reported</div></li><li class="half_rhythm"><div>Allelic w/AD pure HSP</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/611225" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">611225</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.alazami.2011.333" rid="hsp.REF.alazami.2011.333">Alazami et al [2011]</a>, <a class="bibr" href="#hsp.REF.y_ld_r_m.2011.1886" rid="hsp.REF.y_ld_r_m.2011.1886">Y&#x00131;ld&#x00131;r&#x00131;m et al [2011]</a>, <a class="bibr" href="#hsp.REF.alsaif.2012.510" rid="hsp.REF.alsaif.2012.510">Al-Saif et al [2012]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>FA2H</i>&#x000a0;<sup>4</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG35</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Seizures</div></li><li class="half_rhythm"><div>Dystonia</div></li><li class="half_rhythm"><div>Parkinsonism w/iron accumulation in basal ganglia</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/612319" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">612319</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.edvardson.2008.643" rid="hsp.REF.edvardson.2008.643">Edvardson et al [2008]</a>, <a class="bibr" href="#hsp.REF.dick.2010.e1251" rid="hsp.REF.dick.2010.e1251">Dick et al [2010]</a>, <a class="bibr" href="#hsp.REF.pensato.2014.1907" rid="hsp.REF.pensato.2014.1907">Pensato et al [2014]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>GAD1</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not assigned</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Moderate to severe ID</div></li><li class="half_rhythm"><div>Single reported family was described as having AR cerebral palsy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare (single family reported)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.lynex.2004.20" rid="hsp.REF.lynex.2004.20">Lynex et al [2004]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>GBA2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG46</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Hearing loss</div></li><li class="half_rhythm"><div>Polyneuropathy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/614409" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">614409</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.hammer.2013.245" rid="hsp.REF.hammer.2013.245">Hammer et al [2013]</a>, <a class="bibr" href="#hsp.REF.coarelli.2018.60" rid="hsp.REF.coarelli.2018.60">Coarelli et al [2018]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>GJC2</i>&#x000a0;<sup>5</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG44</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Febrile seizures</div></li><li class="half_rhythm"><div>Deafness</div></li><li class="half_rhythm"><div>Episodic spasms</div></li><li class="half_rhythm"><div>Variable degree of leukodystrophy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/613206" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">613206</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.uhlenberg.2004.251" rid="hsp.REF.uhlenberg.2004.251">Uhlenberg et al [2004]</a>, <a class="bibr" href="#hsp.REF.orthmannmurphy.2009.426" rid="hsp.REF.orthmannmurphy.2009.426">Orthmann-Murphy et al [2009]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>GRID2</i>&#x000a0;<sup>6</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not assigned</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Amyotrophy</div></li><li class="half_rhythm"><div>Ataxia</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.utine.2013.926" rid="hsp.REF.utine.2013.926">Utine et al [2013]</a>, <a class="bibr" href="#hsp.REF.maier.2014.289" rid="hsp.REF.maier.2014.289">Maier et al [2014]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>IBA57</i>&#x000a0;<sup>7</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG74</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Optic atrophy</div></li><li class="half_rhythm"><div>Peripheral neuropathy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/616451" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">616451</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.lossos.2015.659" rid="hsp.REF.lossos.2015.659">Lossos et al [2015]</a>, <a class="bibr" href="#hsp.REF.torraco.2017.102" rid="hsp.REF.torraco.2017.102">Torraco et al [2017]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>KIF1A</i>&#x000a0;<sup>8</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG30</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Spastic ataxia</div></li><li class="half_rhythm"><div>Polyneuropathy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/610357" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">610357</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.hamdan.2011.306" rid="hsp.REF.hamdan.2011.306">Hamdan et al [2011]</a>, <a class="bibr" href="#hsp.REF.rivi_re.2011.219" rid="hsp.REF.rivi_re.2011.219">Rivi&#x000e8;re et al [2011]</a>, <a class="bibr" href="#hsp.REF.klebe.2012.645" rid="hsp.REF.klebe.2012.645">Klebe et al [2012]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>KIF1C</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG58</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Spastic ataxia</div></li><li class="half_rhythm"><div>Dystonia</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.caballero_oteyza.2014.2007" rid="hsp.REF.caballero_oteyza.2014.2007">Caballero Oteyza et al [2014]</a>, <a class="bibr" href="#hsp.REF.dor.2014.137" rid="hsp.REF.dor.2014.137">Dor et al [2014]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>KLC2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not assigned</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Optic atrophy</div></li><li class="half_rhythm"><div>Neuropathy</div></li><li class="half_rhythm"><div>Contractures in later stages</div></li><li class="half_rhythm"><div>Cognition remains intact</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Rare</div></li><li class="half_rhythm"><div>Also known as spastic paraplegia optic atrophy, &#x00026; neuropathy (SPOAN)</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/609541" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">609541</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.melo.2015.6877" rid="hsp.REF.melo.2015.6877">Melo et al [2015]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>KLC4</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not assigned</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Multiple contractures</div></li><li class="half_rhythm"><div>Variable degree of leukodystrophy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.bayrakli.2015.763" rid="hsp.REF.bayrakli.2015.763">Bayrakli et al [2015]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>MARS1</i>&#x000a0;<sup>9</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG70</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Nephrotic syndrome, polyneuropathy</div></li><li class="half_rhythm"><div>Mild ID</div></li><li class="half_rhythm"><div>Late onset of CMT2 (axonal) type also reported</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.gonzalez.2013.1247" rid="hsp.REF.gonzalez.2013.1247">Gonzalez et al [2013]</a>, <a class="bibr" href="#hsp.REF.novarino.2014.506" rid="hsp.REF.novarino.2014.506">Novarino et al [2014]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>NT5C2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG45</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Optic atrophy</div></li><li class="half_rhythm"><div>Nystagmus</div></li><li class="half_rhythm"><div>Strabismus</div></li><li class="half_rhythm"><div>ID</div></li><li class="half_rhythm"><div>Hypoplastic corpus callosum</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/613162" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">613162</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.novarino.2014.506" rid="hsp.REF.novarino.2014.506">Novarino et al [2014]</a>, <a class="bibr" href="#hsp.REF.elsaid.2017.33" rid="hsp.REF.elsaid.2017.33">Elsaid et al [2017]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>PGAP1</i>&#x000a0;<sup>10</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG67</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe DD</div></li><li class="half_rhythm"><div>Tremor</div></li><li class="half_rhythm"><div>Agenesis of corpus callosum</div></li><li class="half_rhythm"><div>Hypomyelination</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.murakami.2014.e1004320" rid="hsp.REF.murakami.2014.e1004320">Murakami et al [2014]</a>, <a class="bibr" href="#hsp.REF.novarino.2014.506" rid="hsp.REF.novarino.2014.506">Novarino et al [2014]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>PNPLA6</i>&#x000a0;<sup>11</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG39</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Amyotrophy</div></li><li class="half_rhythm"><div>Endocrine abnormalities w/short stature or hypogonadotropic hypogonadism</div></li><li class="half_rhythm"><div>Chorioretinal dystrophy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/pnpla6-dis/?report=reader"><i>PNPLA6</i>-Related Disorders</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.rainier.2008.780" rid="hsp.REF.rainier.2008.780">Rainier et al [2008]</a>, <a class="bibr" href="#hsp.REF.synofzik.2014.69" rid="hsp.REF.synofzik.2014.69">Synofzik et al [2014]</a>,<br /><a class="bibr" href="#hsp.REF.hufnagel.2015.85" rid="hsp.REF.hufnagel.2015.85">Hufnagel et al [2015]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>REEP2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG72</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Musculoskeletal problems</div></li><li class="half_rhythm"><div>Mild postural tremor</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Rare</div></li><li class="half_rhythm"><div>Inheritance can be dominant or recessive.</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/615625" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">615625</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.esteves.2014.268" rid="hsp.REF.esteves.2014.268">Esteves et al [2014]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>SPART</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG20</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Juvenile</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Distal amyotrophy</div></li><li class="half_rhythm"><div>Short stature</div></li><li class="half_rhythm"><div>Kyphoscoliosis</div></li><li class="half_rhythm"><div>Multiple limb contractures</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Rare</div></li><li class="half_rhythm"><div>Mostly seen among Old Order Amish</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/spg20/?report=reader">Troyer Syndrome</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.cross.1967b.473" rid="hsp.REF.cross.1967b.473">Cross &#x00026; McKusick, [1967b]</a>, <a class="bibr" href="#hsp.REF.patel.2002.347" rid="hsp.REF.patel.2002.347">Patel et al [2002]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>SPG7</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG7</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated or complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Juvenile or adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Dysarthria</div></li><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Optic atrophy</div></li><li class="half_rhythm"><div>Supranuclear palsy</div></li><li class="half_rhythm"><div>Mitochondrial abnormalities on skeletal muscle biopsy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>5%-12% of AR HSP</div></li><li class="half_rhythm"><div>AD inheritance suggested for some pathogenic variants; this remains controversial</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/spg7/?report=reader">Spastic Paraplegia 7</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.casari.1998.973" rid="hsp.REF.casari.1998.973">Casari et al [1998]</a>, <a class="bibr" href="#hsp.REF.mcdermott.2001.467" rid="hsp.REF.mcdermott.2001.467">McDermott et al [2001]</a>, <a class="bibr" href="#hsp.REF.arnoldi.2008.522" rid="hsp.REF.arnoldi.2008.522">Arnoldi et al [2008]</a>, <a class="bibr" href="#hsp.REF.brugman.2008.1500" rid="hsp.REF.brugman.2008.1500">Brugman et al [2008]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>SPG11</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG11</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood or early adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Optic atrophy</div></li><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Pseudobulbar signs</div></li><li class="half_rhythm"><div>Polyneuropathy</div></li><li class="half_rhythm"><div>Levodopa-responsive parkinsonism</div></li><li class="half_rhythm"><div>Hypoplastic or absent corpus callosum</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>5% of AR HSP</div></li><li class="half_rhythm"><div>75% of HSP w/DD &#x00026; hypoplasia of corpus callosum</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/spg11/?report=reader">Spastic Paraplegia 11</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.stevanin.2007.366" rid="hsp.REF.stevanin.2007.366">Stevanin et al [2007]</a>, <a class="bibr" href="#hsp.REF.paisanruiz.2008.1384" rid="hsp.REF.paisanruiz.2008.1384">Paisan-Ruiz et al [2008]</a>, <a class="bibr" href="#hsp.REF.riverol.2009.52" rid="hsp.REF.riverol.2009.52">Riverol et al [2009]</a>, <a class="bibr" href="#hsp.REF.guidubaldi.2011.553" rid="hsp.REF.guidubaldi.2011.553">Guidubaldi et al [2011]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>TECPR2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG49</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Central apnea</div></li><li class="half_rhythm"><div>Severe DD</div></li><li class="half_rhythm"><div>Microcephaly</div></li><li class="half_rhythm"><div>Dysmorphic features</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/tecpr2-hsan-id/?report=reader"><i>TECPR2</i>-HSAN with ID</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.ozlevi.2012.1065" rid="hsp.REF.ozlevi.2012.1065">Oz-Levi et al [2012]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>TFG</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG57</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Optic atrophy</div></li><li class="half_rhythm"><div>Severe polyneuropathy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/615658" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">615658</a></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.beetz.2013.5091" rid="hsp.REF.beetz.2013.5091">Beetz et al [2013]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>USP8</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG59</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Uncomplicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.novarino.2014.506" rid="hsp.REF.novarino.2014.506">Novarino et al [2014]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>WDR48</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG60</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Polyneuropathy</div></li><li class="half_rhythm"><div>DD</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a class="bibr" href="#hsp.REF.novarino.2014.506" rid="hsp.REF.novarino.2014.506">Novarino et al [2014]</a>
</td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ZFYVE26</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG15</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood or early adulthood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>DD</div></li><li class="half_rhythm"><div>Optic atrophy</div></li><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Central retinal degeneration</div></li><li class="half_rhythm"><div>Polyneuropathy</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1%-2% of AR HSP</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/spg15/?report=reader">Spastic Paraplegia 15</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.hanein.2008.992" rid="hsp.REF.hanein.2008.992">Hanein et al [2008]</a>, <a class="bibr" href="#hsp.REF.pensato.2014.1907" rid="hsp.REF.pensato.2014.1907">Pensato et al [2014]</a></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; ALS = amyotrophic lateral sclerosis; DD = developmental delay; HSP = hereditary spastic paraplegia; ID = intellectual disability; <i>TECPR2</i>-HSAN with ID = <i>TECPR2</i>-related hereditary sensory and autonomic neuropathy with intellectual disability</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="hsp.TF.2.1"><p class="no_margin">Genes are listed alphabetically.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="hsp.TF.2.2"><p class="no_margin">Allelic with pontocerebellar hypoplasia type 9</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="hsp.TF.2.3"><p class="no_margin">
<a class="bibr" href="#hsp.REF.goizet.2009.1589" rid="hsp.REF.goizet.2009.1589">Goizet et al [2009]</a>
</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="hsp.TF.2.4"><p class="no_margin">Allelic with <a href="/books/n/gene/fahn/?report=reader">fatty acid hydroxylase-associated neurodegeneration</a> and leukodystrophy</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="hsp.TF.2.5"><p class="no_margin">Allelic with <a href="/books/n/gene/pmld1/?report=reader">Pelizaeus-Merzbacher-like disease 1</a> and hereditary lymphedema type IC</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="hsp.TF.2.6"><p class="no_margin">Allelic with autosomal recessive spinocerebellar ataxia 18 (See <a href="/books/n/gene/ataxias/?report=reader">Hereditary Ataxia Overview</a>.)</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="hsp.TF.2.7"><p class="no_margin">Allelic with multiple mitochondrial dysfunctions syndrome 3</p></div></dd></dl><dl class="bkr_refwrap"><dt>8. </dt><dd><div id="hsp.TF.2.8"><p class="no_margin">Allelic with <a href="/books/n/gene/hsan2/?report=reader">hereditary sensory and autonomic neuropathy type 2C</a> and AD intellectual disability type 9</p></div></dd></dl><dl class="bkr_refwrap"><dt>9. </dt><dd><div id="hsp.TF.2.9"><p class="no_margin">Allelic with <a href="/books/n/gene/cmt/?report=reader">Charcot-Marie-Tooth neuropathy type 2U</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>10. </dt><dd><div id="hsp.TF.2.10"><p class="no_margin">Allelic with autosomal recessive intellectual disability type 42</p></div></dd></dl><dl class="bkr_refwrap"><dt>11. </dt><dd><div id="hsp.TF.2.11"><p class="no_margin">Allelic with Boucher-Neuhauser syndrome, Gordon-Holmes syndrome, Oliver-McFarlane syndrome, and Laurence-Moon syndrome</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhspThereditaryspasticparaplegiagene2"><div id="hsp.T.hereditary_spastic_paraplegia_gene_2" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Hereditary Spastic Paraplegia: Genes and Distinguishing Clinical Features &#x02013; X-Linked Inheritance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hsp.T.hereditary_spastic_paraplegia_gene_2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_1" rowspan="2" scope="rowgroup" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene&#x000a0;<sup>1</sup></th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_2" style="text-align:left;vertical-align:middle;">HSP Designation</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_3" style="text-align:left;vertical-align:middle;">Type of HSP</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_4" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_4" style="text-align:left;vertical-align:middle;">Onset</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_5" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_5" style="text-align:left;vertical-align:middle;">Distinguishing Clinical Features</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_6" rowspan="2" scope="col" colspan="1" headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_6" style="text-align:left;vertical-align:middle;">Other</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_7" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">References</th></tr><tr><th headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_7" id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;"><i>GeneReview</i><br />or OMIM Entry</th><th headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_7" id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Citation</th></tr></thead><tbody><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>L1CAM</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG1&#x000a0;<sup>2</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infancy</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>ID</div></li><li class="half_rhythm"><div>Adducted thumbs</div></li><li class="half_rhythm"><div>Corpus callosum hypoplasia</div></li><li class="half_rhythm"><div>Aphasia</div></li><li class="half_rhythm"><div>Obstructive hydrocephalus</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/l1cam/?report=reader">L1 Syndrome</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.jouet.1994.402" rid="hsp.REF.jouet.1994.402">Jouet et al [1994]</a>, <a class="bibr" href="#hsp.REF.schranderstumpel.1995.107" rid="hsp.REF.schranderstumpel.1995.107">Schrander-Stumpel et al [1995]</a>, <a class="bibr" href="#hsp.REF.yamasaki.1995.50" rid="hsp.REF.yamasaki.1995.50">Yamasaki et al [1995]</a>, <a class="bibr" href="#hsp.REF.finckh.2000.40" rid="hsp.REF.finckh.2000.40">Finckh et al [2000]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>PLP1</i>&#x000a0;<sup>3</sup></td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG2</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early-childhood to juvenile onset<br />(in manifesting female heterozygotes: onset in 4th-7th decade)</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Pure HSP phenotype present in early stages; later, other signs emerge</div></li><li class="half_rhythm"><div>Nystagmus</div></li><li class="half_rhythm"><div>Optic atrophy</div></li><li class="half_rhythm"><div>Dysarthria</div></li><li class="half_rhythm"><div>ID</div></li><li class="half_rhythm"><div>Variable degree of leukodystrophy on MRI</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Rare</div></li><li class="half_rhythm"><div>In heterozygous females: variable phenotype w/relatively late onset &#x00026; mild clinical manifestations</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/pmd/?report=reader"><i>PLP1</i>-Related Disorders</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.saugierveber.1994.257" rid="hsp.REF.saugierveber.1994.257">Saugier-Veber et al [1994]</a>, <a class="bibr" href="#hsp.REF.cambi.1996.1112" rid="hsp.REF.cambi.1996.1112">Cambi et al [1996]</a>, <a class="bibr" href="#hsp.REF.hodes.1999.132" rid="hsp.REF.hodes.1999.132">Hodes et al [1999]</a>, <a class="bibr" href="#hsp.REF.sivakumar.1999.680" rid="hsp.REF.sivakumar.1999.680">Sivakumar et al [1999]</a></td></tr><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>SLC16A2</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SPG22</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early childhood</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe ID</div></li><li class="half_rhythm"><div>Infantile hypotonia</div></li><li class="half_rhythm"><div>Progressive spasticity</div></li><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Dystonia</div></li><li class="half_rhythm"><div>&#x02191; T3 &#x00026; normal to mildly &#x02191; TSH</div></li><li class="half_rhythm"><div>&#x02193; T4 hypomyelination on neuroimaging</div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Rare</div></li><li class="half_rhythm"><div>SPG22 is a proposed designation.&#x000a0;<sup>4</sup></div></li><li class="half_rhythm"><div>Also referred to as Allan-Herndon-Dudley syndrome&#x000a0;<sup>5</sup></div></li></ul>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/thctd/?report=reader">Allan-Herndon-Dudley Syndrome</a>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_1_7 hd_h_hsp.T.hereditary_spastic_paraplegia_gene_2_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#hsp.REF.dumitrescu.2004.168" rid="hsp.REF.dumitrescu.2004.168">Dumitrescu et al [2004]</a>, <a class="bibr" href="#hsp.REF.boccone.2010.392" rid="hsp.REF.boccone.2010.392">Boccone et al [2010]</a></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; HSP = hereditary spastic paraplegia; ID = intellectual disability</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="hsp.TF.3.1"><p class="no_margin">Genes are listed alphabetically.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="hsp.TF.3.2"><p class="no_margin">SPG1 is more commonly referred to as MASA syndrome (<i>m</i>ental retardation [intellectual disability], <i>a</i>phasia [delayed speech], <i>s</i>pastic paraplegia, <i>a</i>dducted thumbs). Allelic disorders are X-linked hydrocephalus with stenosis of the aqueduct of Sylvius and X-linked complicated corpus callosum agenesis.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="hsp.TF.3.3"><p class="no_margin">Allelic with <a href="/books/n/gene/pmd/?report=reader">Pelizaeus-Merzbacher disease</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="hsp.TF.3.4"><p class="no_margin">OMIM <a href="https://www.omim.org/entry/300523" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">300523</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="hsp.TF.3.5"><p class="no_margin">Because of the overlap between the clinical phenotype in individuals with <i>SLC16A2</i> abnormalities and in those with a previously described syndrome, Allan-Herndon-Dudley syndrome (AHDS), <a class="bibr" href="#hsp.REF.schwartz.2005.41" rid="hsp.REF.schwartz.2005.41">Schwartz et al [2005]</a> analyzed <i>SLC16A2</i> in six families with AHDS. <i>SLC16A2</i> pathogenic variants were identified in all six; therefore, AHDS is now synonymous with MCT8-specific thyroid hormone cell-membrane transporter deficiency due to pathogenic variants in <i>SLC16A2</i> (see <a href="/books/n/gene/thctd/?report=reader">Allan-Herndon-Dudley Syndrome</a>).</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhspThereditaryspasticparaplegiagene3"><div id="hsp.T.hereditary_spastic_paraplegia_gene_3" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Hereditary Spastic Paraplegia: Gene and Distinguishing Clinical Features &#x02013; Maternal (Mitochondrial) Inheritance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1509/table/hsp.T.hereditary_spastic_paraplegia_gene_3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hsp.T.hereditary_spastic_paraplegia_gene_3_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_3_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_3_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">HSP Designation</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_3_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Type of HSP</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_3_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Onset</th><th id="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_3_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing Clinical Features</th></tr></thead><tbody><tr><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_3_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>MT-ATP6</i>
</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not assigned</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complicated</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adult</td><td headers="hd_h_hsp.T.hereditary_spastic_paraplegia_gene_3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardiomyopathy, diabetes mellitus, sensory polyneuropathy</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">
<a class="bibr" href="#hsp.REF.verny.2011.70" rid="hsp.REF.verny.2011.70">Verny et al [2011]</a>
</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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