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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Hutchinson-Gilford Progeria Syndrome" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2025/03/13" /><meta name="citation_author" content="Leslie B Gordon" /><meta name="citation_author" content="W Ted Brown" /><meta name="citation_author" content="Francis S Collins" /><meta name="citation_pmid" content="20301300" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1121/" /><meta name="citation_keywords" content="Hutchinson-Gilford Progeria Syndrome (HGPS), Classic" /><meta name="citation_keywords" content="Atypical Hutchinson-Gilford Progeria Syndrome" /><meta name="citation_keywords" content="Prelamin-A/C" /><meta name="citation_keywords" content="LMNA" /><meta name="citation_keywords" content="Hutchinson-Gilford Progeria Syndrome" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Hutchinson-Gilford Progeria Syndrome" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Leslie B Gordon" /><meta name="DC.Contributor" content="W Ted Brown" /><meta name="DC.Contributor" content="Francis S Collins" /><meta name="DC.Date" content="2025/03/13" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK1121/" /><meta name="description" content="Hutchinson-Gilford progeria syndrome (HGPS) is characterized in the first year of life by growth deficiency, lagophthalmos, hair loss, delayed and incomplete primary tooth eruption, subcutaneous fat loss, and areas of abnormal skin (tightness, stippling, and/or small outpouchings over the abdomen and upper thighs). Motor and mental development is normal. Children have profound growth failure, subcutaneous lipodystrophy, total alopecia, high-pitched voice, nail dystrophy, horse-riding stance, coxa valga with possible hip dislocations, narrowed upper thorax, and progressive joint contractures. Characteristic facial features include disproportionately large head for the face, narrow nasal ridge, narrow nasal tip, thin vermilion of the lips, small mouth, retro- and micrognathia, delayed loss of primary teeth, and partial secondary tooth eruption. Additional features include low-frequency conductive hearing loss, dry eye with risk of exposure keratitis, and premature and accelerated atherosclerosis with cerebrovascular and cardiovascular disease. Without lonafarnib treatment death occurs at an average age of 14.5 years (range: 6-20 years). With lonafarnib treatment average life span is extended to approximately 18.7 years." /><meta name="og:title" content="Hutchinson-Gilford Progeria Syndrome" /><meta name="og:type" content="book" /><meta name="og:description" content="Hutchinson-Gilford progeria syndrome (HGPS) is characterized in the first year of life by growth deficiency, lagophthalmos, hair loss, delayed and incomplete primary tooth eruption, subcutaneous fat loss, and areas of abnormal skin (tightness, stippling, and/or small outpouchings over the abdomen and upper thighs). Motor and mental development is normal. Children have profound growth failure, subcutaneous lipodystrophy, total alopecia, high-pitched voice, nail dystrophy, horse-riding stance, coxa valga with possible hip dislocations, narrowed upper thorax, and progressive joint contractures. Characteristic facial features include disproportionately large head for the face, narrow nasal ridge, narrow nasal tip, thin vermilion of the lips, small mouth, retro- and micrognathia, delayed loss of primary teeth, and partial secondary tooth eruption. Additional features include low-frequency conductive hearing loss, dry eye with risk of exposure keratitis, and premature and accelerated atherosclerosis with cerebrovascular and cardiovascular disease. Without lonafarnib treatment death occurs at an average age of 14.5 years (range: 6-20 years). 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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All GeneReviews" href="/books/n/gene/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" alt="Cover of GeneReviews®" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>GeneReviews<sup>®</sup> [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK1121_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK1121_dtls__"><div>Adam MP, Feldman J, Mirzaa GM, et al., editors.</div><div>Seattle (WA): <a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>; 1993-2025.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/gene/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search GeneReviews" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search GeneReviews" submit="false" style="padding: 0.1em 0.4em;" /></div></form><div><ul class="inline_list"><li><a href="/books/n/gene/advanced/">GeneReviews Advanced Search</a></li><li style="margin-left:.5em"><a href="/books/n/gene/helpadvsearch/">Help</a></li></ul></div></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/huppke-brendel/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/sys-h/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK1121_"><span class="title" itemprop="name">Hutchinson-Gilford Progeria Syndrome</span></h1><p class="contrib-group"><span itemprop="author">Leslie B Gordon</span>, MD, PhD, <span itemprop="author">W Ted Brown</span>, MD, PhD, and <span itemprop="author">Francis S Collins</span>, MD, PhD.</p><a data-jig="ncbitoggler" href="#__NBK1121_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK1121_ai__"><div class="contrib half_rhythm"><span itemprop="author">Leslie B Gordon</span>, MD, PhD<div class="affiliation small">Department of Pediatrics<br />Alpert Medical School of Brown University<br />Providence, Rhode Island<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.hcraeserairegorp@nodrogl" class="oemail">gro.hcraeserairegorp@nodrogl</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">W Ted Brown</span>, MD, PhD<div class="affiliation small">Institute for Basic Research in Developmental Disabilities<br />Staten Island, New York<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.loa@rbibtw" class="oemail">moc.loa@rbibtw</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Francis S Collins</span>, MD, PhD<div class="affiliation small">Senior Investigator, National Institutes of Health<br />Bethesda, Maryland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin@snilloc.sicnarf" class="oemail">vog.hin@snilloc.sicnarf</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">December 12, 2003</span>; Last Update: <span itemprop="dateModified">March 13, 2025</span>.</p><p><em>Estimated reading time: 33 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="hgps.Summary" itemprop="description"><h2 id="_hgps_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Hutchinson-Gilford progeria syndrome (HGPS) is characterized in the first year of life by growth deficiency, lagophthalmos, hair loss, delayed and incomplete primary tooth eruption, subcutaneous fat loss, and areas of abnormal skin (tightness, stippling, and/or small outpouchings over the abdomen and upper thighs). Motor and mental development is normal. Children have profound growth failure, subcutaneous lipodystrophy, total alopecia, high-pitched voice, nail dystrophy, horse-riding stance, coxa valga with possible hip dislocations, narrowed upper thorax, and progressive joint contractures. Characteristic facial features include disproportionately large head for the face, narrow nasal ridge, narrow nasal tip, thin vermilion of the lips, small mouth, retro- and micrognathia, delayed loss of primary teeth, and partial secondary tooth eruption. Additional features include low-frequency conductive hearing loss, dry eye with risk of exposure keratitis, and premature and accelerated atherosclerosis with cerebrovascular and cardiovascular disease. Without lonafarnib treatment death occurs at an average age of 14.5 years (range: 6-20 years). With lonafarnib treatment average life span is extended to approximately 18.7 years.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of classic or nonclassic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> HGPS is established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with characteristic clinical features and a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>LMNA</i> that results in production of progerin, the disease-causing abnormal lamin A protein, identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>. Individuals with classic genotype HGPS are heterozygous for pathogenic variant c.1824C>T (~90% of individuals). Individuals with nonclassic genotype HGPS are heterozygous for another <i>LMNA</i> pathogenic variant in <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 11 or <a class="def" href="/books/n/gene/glossary/def-item/intron/">intron</a> 11 that results in production of progerin (~10% of individuals).</p></div><div><h4 class="inline">Management.</h4><p><i>Targeted therapy:</i> Lonafarnib results in increase in life span presumably due to slowed cardiovascular disease progression that includes improved arterial wall stiffness and carotid-femoral pulse wave velocity. The therapy also improves low-tone hearing and may decrease headache frequency. Side effects are primarily gastrointestinal and vary in severity and duration.</p><p><i>Supportive care:</i> Frequent small meals to maximize caloric intake; daily multivitamin; medication dosages are based on body weight or body surface area, not age; shoe pads for foot discomfort; school adaptations for short stature. General anesthesia and intubation should be performed with extreme caution, with fiberoptic intubation if possible. Fluoride supplementation as needed; if secondary teeth erupt palatally displaced, primary tooth extractions after the secondary teeth have erupted and/or fully descended may be required to avoid dental crowding. Sunscreen on exposed areas of skin, including the head, during outdoor activities; encourage sun-protective clothing including hat. Hip dislocation is best managed with physical therapy and body bracing; reconstructive hip surgery is possible, but comorbidities of surgery in this high-risk population should be considered. Routine treatment for bone fractures; physical and occupational therapy to maintain joint mobility, active stretching and strengthening exercises, and hydrotherapy. Though menstruation is highly variable, in females with excessive pubertal vaginal bleeding, short-term low-dose oral contraceptives can be used to decrease blood loss. Healthy diet with regular physical activity as tolerated; maintain optimal hydration, especially during hot weather and airplane travel. Low-dose aspirin to prevent cardiovascular and neurovascular complications. Nitroglycerin can be beneficial for angina; anti-congestive therapy is routine for the treatment of congestive heart failure. Modified transcatheter aortic valve replacement or modified apico-aortic valve replacement are high-risk interventions to treat critical aortic stenosis. Exercise, diet modification, and statin therapy as needed for hyperlipidemia. Hearing aids can be used when clinically necessary. Exposure keratopathy can be treated with ocular lubrication. Social work and family support.</p><p><i>Surveillance:</i> Assess growth, caloric intake, skin manifestations, and family needs at each visit. Blood pressure, EKG, echocardiogram, and carotid scan every six to 12 months. Dental examination with radiographs, orthopedic evaluation, occupational and physical therapy assessment, lipid profile, neurologic assessment with head and neck MRI/MRA, and ophthalmology and audiology evaluation annually.</p><p><i>Agents/circumstances to avoid:</i> Large crowds with taller and/or larger peers because of the risk of injury; trampolines and bouncy houses due to risk of hip dislocation; dehydration, anemia, and high fever because of cardiac and stroke risks; calcium supplementation because of extraskeletal calcium deposits.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>HGPS is an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> disorder. Ninety-eight percent of individuals with HGPS have the disorder as the result of a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>
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<i>LMNA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. Approximately 2% of individuals have the disorder as the result of a pathogenic variant inherited from an unaffected parent with <a class="def" href="/books/n/gene/glossary/def-item/gonadal-mosaicism/">gonadal mosaicism</a>. Because HGPS is typically caused by a <i>de novo</i> pathogenic variant, the <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> to the sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> is low but not zero because of the possibility of parental gonadal mosaicism. Once the <i>LMNA</i> pathogenic variant has been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p></div></div><div id="hgps.GeneReview_Scope"><h2 id="_hgps_GeneReview_Scope_"><i>GeneReview</i> Scope</h2><div id="hgps.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1121/table/hgps.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hgps.Tc_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hgps.Tc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hutchinson-Gilford Progeria Syndrome: Included Genotypes</th></tr></thead><tbody><tr><td headers="hd_h_hgps.Tc_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hutchinson-Gilford progeria syndrome, classic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a></div></li><li class="half_rhythm"><div>Hutchinson-Gilford progeria syndrome, nonclassic genotypes</div></li></ul>
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</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">For synonyms and outdated names see <a href="#hgps.Nomenclature">Nomenclature</a>.</p></div></dd></dl></div></div></div></div><div id="hgps.Diagnosis"><h2 id="_hgps_Diagnosis_">Diagnosis</h2><p>The clinical diagnosis of Hutchinson-Gilford progeria syndrome (HGPS) can be established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> when characteristic pathognomonic features emerge. Molecular testing should accompany a clinical diagnosis (see <a href="#hgps.Establishing_the_Diagnosis">Establishing the Diagnosis</a>).</p><div id="hgps.Suggestive_Findings"><h3>Suggestive Findings</h3><p>HGPS <b>should be suspected</b> in probands with the following clinical and radiographic findings in the setting of normal intellectual development (see <a class="figpopup" href="/books/NBK1121/figure/hgps.F1/?report=objectonly" target="object" rid-figpopup="fighgpsF1" rid-ob="figobhgpsF1">Figure 1</a> and <a class="figpopup" href="/books/NBK1121/figure/hgps.F2/?report=objectonly" target="object" rid-figpopup="fighgpsF2" rid-ob="figobhgpsF2">Figure 2</a>).</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="fighgpsF1" co-legend-rid="figlgndhgpsF1"><a href="/books/NBK1121/figure/hgps.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="fighgpsF1" rid-ob="figobhgpsF1"><img class="small-thumb" src="/books/NBK1121/bin/hgps-Image001.gif" src-large="/books/NBK1121/bin/hgps-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndhgpsF1"><h4 id="hgps.F1"><a href="/books/NBK1121/figure/hgps.F1/?report=objectonly" target="object" rid-ob="figobhgpsF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Female age 11 years and male age six years with Hutchinson-Gilford progeria syndrome displaying characteristic facial features, with total alopecia, lipodystrophy, long, narrow nose with narrow nasal ridge and narrow nasal tip, small mouth, and retrognathia <a href="/books/NBK1121/figure/hgps.F1/?report=objectonly" target="object" rid-ob="figobhgpsF1">(more...)</a></p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="fighgpsF2" co-legend-rid="figlgndhgpsF2"><a href="/books/NBK1121/figure/hgps.F2/?report=objectonly" target="object" title="Figure 2. " class="img_link icnblk_img figpopup" rid-figpopup="fighgpsF2" rid-ob="figobhgpsF2"><img class="small-thumb" src="/books/NBK1121/bin/hgps-Image002.gif" src-large="/books/NBK1121/bin/hgps-Image002.jpg" alt="Figure 2. " /></a><div class="icnblk_cntnt" id="figlgndhgpsF2"><h4 id="hgps.F2"><a href="/books/NBK1121/figure/hgps.F2/?report=objectonly" target="object" rid-ob="figobhgpsF2">Figure 2. </a></h4><p class="float-caption no_bottom_margin">Clinical, imaging, and growth features of Hutchinson-Gilford progeria syndrome (HGPS) A. Girl age three months</p></div></div><p>
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<b>Growth deficiency</b>
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</p><ul><li class="half_rhythm"><div>Typically postnatal onset during first two years of life</div></li><li class="half_rhythm"><div>Short stature (<3rd centile)</div></li><li class="half_rhythm"><div>Poor weight gain (<3rd centile); weight distinctly low for height</div></li><li class="half_rhythm"><div>Diminished subcutaneous body fat globally, along with low serum leptin levels</div></li></ul><p><b>Facial features</b> that develop in childhood (See <a class="figpopup" href="/books/NBK1121/figure/hgps.F1/?report=objectonly" target="object" rid-figpopup="fighgpsF1" rid-ob="figobhgpsF1">Figure 1</a>.)</p><ul><li class="half_rhythm"><div>Head disproportionately large for face</div></li><li class="half_rhythm"><div>Long, narrow nose (narrow nasal ridge and narrow nasal tip)</div></li><li class="half_rhythm"><div>Thin vermilion of the upper and lower lips</div></li><li class="half_rhythm"><div>Small mouth, retrognathia, and micrognathia</div></li></ul><p>
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<b>Ectodermal findings</b>
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</p><ul><li class="half_rhythm"><div>Dental. Delayed eruption and delayed loss of primary teeth, partial secondary tooth eruption, tooth misalignment</div></li><li class="half_rhythm"><div>Skin. Taut, variably pigmented, sclerodermatous skin outpouchings over lower abdomen and/or proximal thighs, any of which can be the first signs of disease in infancy</div></li><li class="half_rhythm"><div>Hair. Total alopecia that develops in the first two years of life, sometimes with very sparse, downy, immature hair remaining; loss of eyebrows</div></li><li class="half_rhythm"><div>Dystrophic nails develop at variable ages in childhood.</div></li></ul><p>
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<b>Musculoskeletal clinical and radiographic findings</b>
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</p><ul><li class="half_rhythm"><div>Coxa valga develops within the first three years, with wide-based, shuffling gait, sometimes accompanied by avascular necrosis of the femoral head.</div></li><li class="half_rhythm"><div>Osteolysis of the distal phalanges</div></li><li class="half_rhythm"><div>Short clavicles with distal resorption/tapering (distal clavicular osteolysis)</div></li><li class="half_rhythm"><div>Pear-shaped thorax</div></li><li class="half_rhythm"><div>Normal or mildly low bone density z scores when normalized for height and age</div></li><li class="half_rhythm"><div>Joint contractures are present in all individuals; can be present at birth or present later in childhood; locations vary</div></li></ul><p>
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<b>Other findings</b>
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</p><ul><li class="half_rhythm"><div>Nocturnal lagophthalmos (the inability to fully close the eyes while sleeping) is an almost uniform finding and can occur from birth.</div></li><li class="half_rhythm"><div>Normal intellectual development</div></li><li class="half_rhythm"><div>High-pitched voice</div></li><li class="half_rhythm"><div>Low-frequency conductive hearing loss</div></li><li class="half_rhythm"><div>Secondary sexual characteristics do not fully develop. Menstruation is variable in females.</div></li></ul></div><div id="hgps.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><div id="hgps.Clinical_Diagnosis"><h4>Clinical Diagnosis</h4><p>The clinical diagnosis of Hutchinson-Gilford progeria syndrome (HGPS) can be established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> when characteristic pathognomonic features emerge. These include, at a minimum, one of the skin findings, severe growth failure, alopecia, global lipodystrophy, and small clavicles, all present in the setting of normal intellectual development and within the first two years of life. Although these findings can establish the clinical diagnosis of HGPS, the lack of or delay in these findings does not exclude the diagnosis, as nonclassic and classic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> HGPS can vary in the onset of these findings. Molecular testing should accompany a clinical diagnosis.</p></div><div id="hgps.Molecular_Diagnosis"><h4>Molecular Diagnosis</h4><p>Four major categories help to define <i>LMNA</i>-related disorders. Categories 1 and 2 define HGPS; categories 3 and 4 are not considered HGPS:</p><dl class="temp-labeled-list"><dt>1.</dt><dd><p class="no_top_margin">Progerin-producing classic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> HGPS</p></dd><dt>2.</dt><dd><p class="no_top_margin">Progerin-producing nonclassic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> HGPS</p></dd><dt>3.</dt><dd><p class="no_top_margin">Non-progerin-producing progeroid laminopathies (see <a href="#hgps.Differential_Diagnosis">Differential Diagnosis</a>) due to:</p><ul><li class="half_rhythm"><div>Heterozygous or <a class="def" href="/books/n/gene/glossary/def-item/biallelic/">biallelic</a> <i>LMNA</i> pathogenic variants that do not result in progerin production but result in phenotypic overlap with progerin-producing HGPS</div></li><li class="half_rhythm"><div>Pathogenic variants in <i>ZMPSTE24</i> that cause prelamin A processing deficiency and result in phenotypic overlap with progerin-producing HGPS</div></li></ul></dd><dt>4.</dt><dd><p class="no_top_margin">Non-progeroid laminopathies (See <a href="#hgps.Genetically_Related_Allelic_Disorde">Genetically Related Disorders</a>.)</p></dd></dl><p>HGPS is caused by the production of an abnormal form of lamin A protein called progerin. Progerin results from increased spliceosome binding ratio between an <i>LMNA</i> cryptic internal exonic splice sequence at c.1818-1824 and the <a class="def" href="/books/n/gene/glossary/def-item/intron/">intron</a> 11 recognition site normally used to remove intron 11 from the lamin A pre-<a class="def" href="/books/n/gene/glossary/def-item/mrna/">mRNA</a> transcript. Exonic missplicing results in a 150-<a class="def" href="/books/n/gene/glossary/def-item/base-pair/">base pair</a> <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> in the mRNA, and a 50-amino acid deletion in prelamin A protein. See <a href="/books/NBK1121/table/hgps.T.classic_and_nonclassic_genotype_h/?report=objectonly" target="object" rid-ob="figobhgpsTclassicandnonclassicgenotypeh">Table 2</a> for identified classic and nonclassic HGPS genotypes.</p><p>The diagnosis of <b>classic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> HGPS is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> <a href="#hgps.Suggestive_Findings">suggestive findings</a> and a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">c.1824C>T</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>LMNA</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK1121/table/hgps.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobhgpsTmoleculargenetictestingusedin">Table 1</a>).</p><p>The diagnosis of <b>nonclassic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> HGPS is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with <a href="#hgps.Suggestive_Findings">suggestive findings</a> similar to classic genotype HGPS and a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> progerin-producing <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> that either optimizes a cryptic <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 11 splice donor site or deoptimizes the <a class="def" href="/books/n/gene/glossary/def-item/intron/">intron</a> 11 splice donor site of <i>LMNA</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK1121/table/hgps.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobhgpsTmoleculargenetictestingusedin">Table 1</a>).</p><p>Molecular genetic testing approaches can include a combination of <b><a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted testing</b> (single gene testing, <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a>) and <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (<a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a>, <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a>). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see <a href="#hgps.Option_1">Option 1</a>), whereas comprehensive genomic testing does not (see <a href="#hgps.Option_2">Option 2</a>).</p><div id="hgps.Option_1"><h5>
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<b>Option 1</b>
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</h5><p>
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<b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b>
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</p><ul><li class="half_rhythm"><div>Targeted analysis for classic and nonclassic HGPS can be performed by sequencing <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 11 and at least the first seven bases of <a class="def" href="/books/n/gene/glossary/def-item/intron/">intron</a> 11. This span of bases should be standard for an exon 11 <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> sequencing request. A search for the classic <i>LMNA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> <a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">c.1824C>T</a> (identified in ~90% of individuals with HGPS) and nonclassic <i>LMNA</i> pathogenic variants (see <a href="/books/NBK1121/table/hgps.T.classic_and_nonclassic_genotype_h/?report=objectonly" target="object" rid-ob="figobhgpsTclassicandnonclassicgenotypeh">Table 2</a>) can be performed first in individuals with <a href="#hgps.Suggestive_Findings">suggestive findings</a> of HGPS.</div></li><li class="half_rhythm"><div>Sequence analysis of the entire <i>LMNA</i> <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> can be performed if no <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is found on targeted analysis. Sequence analysis of <a class="def" href="/books/n/gene/glossary/def-item/intron/">intron</a> 11 should be included if this was not already completed with targeted analysis.</div></li><li class="half_rhythm"><div>If no <i>LMNA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is identified on <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <i>ZMPSTE24</i> sequence analysis should be considered.</div></li></ul><p>Note: To date, <i>LMNA</i> deletions and/or duplications have not been reported in individuals with HGPS.</p><p><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>LMNA</i>, <i>ZMPSTE24</i>, and other genes of interest such as those causing non-laminopathy progeroid syndromes (see <a href="#hgps.Differential_Diagnosis">Differential Diagnosis</a>) may be considered to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> 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 <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="hgps.Option_2"><h5>
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<b>Option 2</b>
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</h5><p>When the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> is indistinguishable from many other inherited disorders characterized by a progeroid phenotype, <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> is likely involved. <b>Exome sequencing</b> is most commonly used; <b><a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a></b> is also possible.</p><p>For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div id="hgps.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Hutchinson-Gilford Progeria Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1121/table/hgps.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hgps.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hgps.T.molecular_genetic_testing_used_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_hgps.T.molecular_genetic_testing_used_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_hgps.T.molecular_genetic_testing_used_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Identified by Method</th></tr></thead><tbody><tr><td headers="hd_h_hgps.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="3" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
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||
<i>LMNA</i>
|
||
</td><td headers="hd_h_hgps.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Targeted <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a><br />(incl <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 11 & at least 1st 7 bases of <a class="def" href="/books/n/gene/glossary/def-item/intron/">intron</a> 11)</td><td headers="hd_h_hgps.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100% <sup>3</sup></td></tr><tr><td headers="hd_h_hgps.T.molecular_genetic_testing_used_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>4</sup></td><td headers="hd_h_hgps.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~100% <sup>3, 5</sup></td></tr><tr><td headers="hd_h_hgps.T.molecular_genetic_testing_used_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>6</sup></td><td headers="hd_h_hgps.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None identified</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="hgps.TF.1.1"><p class="no_margin">See <a href="/books/NBK1121/#hgps.molgen.TA">Table A. Genes and Databases</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> and protein.</p></div></dd><dt>2. </dt><dd><div id="hgps.TF.1.2"><p class="no_margin">See <a href="#hgps.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>.</p></div></dd><dt>3. </dt><dd><div id="hgps.TF.1.3"><p class="no_margin">About 90% of individuals with typical clinical features of HGPS will have the classic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> (<a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">c.1824C>T</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>). The remaining ~10% have nonclassic genotypes: a heterozygous <a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">c.1821G>A</a> or <a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">c.1822G>A</a> pathogenic variant or a progerin-producing pathogenic variant in <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 11 or <a class="def" href="/books/n/gene/glossary/def-item/intron/">intron</a> 11 [<a class="bk_pop" href="#hgps.REF.gordon.2018b.1687">Gordon et al 2018b</a>].</p></div></dd><dt>4. </dt><dd><div id="hgps.TF.1.4"><p class="no_margin">Sequence analysis should include <a class="def" href="/books/n/gene/glossary/def-item/intron/">intron</a> 11. Sequence analysis detects variants that are benign, <a class="def" href="/books/n/gene/glossary/def-item/likely-benign/">likely benign</a>, of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>, <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>, or pathogenic. Variants may include <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants and small intragenic deletions/insertions; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions/duplications are not detected. For issues to consider in interpretation of <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>5. </dt><dd><div id="hgps.TF.1.5"><p class="no_margin">An individual with <a class="def" href="/books/n/gene/glossary/def-item/somatic-mosaicism/">somatic mosaicism</a> has been identified using deep sequencing, whereby a child likely manifested two progerin-producing variants in different cells [<a class="bk_pop" href="#hgps.REF.bar.2017.212">Bar et al 2017</a>].</p></div></dd><dt>6. </dt><dd><div id="hgps.TF.1.6"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include a range of techniques such as <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications.</p></div></dd></dl></div></div></div></div></div></div></div><div id="hgps.Clinical_Characteristics"><h2 id="_hgps_Clinical_Characteristics_">Clinical Characteristics</h2><div id="hgps.Clinical_Description"><h3>Clinical Description</h3><p>Classic and nonclassic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> Hutchinson-Gilford progeria syndrome (HGPS) are characterized by growth deficiency, characteristic facial features, dental anomalies, sclerodermatous skin findings, alopecia, lipodystrophy, dystrophic nails, musculoskeletal manifestations, infertility, severe early-onset atherosclerosis, hearing loss, and nocturnal lagophthalmos. Children with progeria usually appear normal at birth and in early infancy.</p><p><b>Growth deficiency.</b> Most infants display normal weight at birth. Profoundly poor weight gain and growth deficiency usually occurs during the first year. Poor weight gain and loss of subcutaneous fat results in weight less than the 3rd centile for age, and weight that is distinctly low for height. Stature also decreases to below the 3rd centile for age. Lack of body fat can contribute to foot discomfort over time.</p><p><b>Characteristic facial features</b> (see <a class="figpopup" href="/books/NBK1121/figure/hgps.F1/?report=objectonly" target="object" rid-figpopup="fighgpsF1" rid-ob="figobhgpsF1">Figure 1</a>) include a head that appears disproportionately large for face, narrow nasal ridge with a narrow nasal tip, thin vermilion of the upper and lower lips, small mouth, retrognathia, and micrognathia. Ogival (steeple-shaped) palatal vault occurs in 60%-70% of affected individuals. A short, thick lingual frenulum that limits tongue mobility is seen in about 50% of affected individuals. Narrow airway and rigid laryngeal structures cause a high-pitched voice.</p><p><b>Dental.</b> Delayed eruption and delayed loss of primary teeth are common. Dental crowding occurs as a result of a small mouth, lack of primary tooth loss, and secondary tooth eruption behind the primary teeth. Secondary tooth eruption is often partial.</p><p><b>Skin.</b> Skin findings may be evident at birth and are present in all individuals by age two years. "Sclerodermatous" skin changes variably include areas that are described as taut, thickened, fibrotic, indurated, or rippled. In addition, dimpling or irregular small outpouchings can occur over the lower abdomen and proximal thighs. Skin also displays abnormal pigmentation consisting of light or dark macules and patches along with some papules and skin mottling.</p><p><b>Hair.</b> Partial alopecia develops in the first year of life and progresses to total alopecia. Sparse, downy hairs may be present on the occiput. Loss of eyebrows is common, and loss of eyelashes occurs in some individuals.</p><p><b>Nails.</b> Fingernails and toenails become dystrophic.</p><p><b>Musculoskeletal</b>. Coxa valga causes a horse-riding stance and wide-based, shuffling gait. Individuals with HGPS are particularly susceptible to hip dislocation because of progressive coxa valga malformation, which can be accompanied by avascular necrosis of the hip. Avascular necrosis can cause hip pain and is evident on radiographs. Additional bone changes include osteolysis of the distal phalanges, short clavicles with distal resorption, a pear-shaped thorax, and mildly low bone density for age. Fractures are not more commonly reported in individuals with HGPS. Extraskeletal calcifications are present in 40% of individuals, with unknown clinical significance. Progressive stiffness of the joints due to tightened joint ligaments and osteoarthritis occurs with variable severity.</p><p><b>Endocrine.</b> Affected individuals do not become sexually mature. Females reach Tanner stage 1 (78%) or 2 (22%) during pubertal years, and approximately 60% of females experience menarche [<a class="bk_pop" href="#hgps.REF.greer.2018.238">Greer et al 2018</a>]. No instances of fertility have been described. Serum leptin concentrations are below the limit of detection. Insulin resistance occurs in about 50% of individuals, without the overt development of diabetes mellitus.</p><p><b>Cardiovascular/cerebrovascular.</b> Individuals with HGPS develop severe atherosclerosis, usually without obvious abnormalities in lipid profiles [<a class="bk_pop" href="#hgps.REF.gordon.2005.336">Gordon et al 2005</a>]. In general, serum cholesterol, low-density lipoprotein (LDL), and triglyceride concentrations are not elevated, and high-density lipoprotein (HDL) concentrations may decrease with age. Diastolic dysfunction and cardiac strain are early cardiac abnormalities, usually detected beyond age five years by tissue Doppler echocardiography [<a class="bk_pop" href="#hgps.REF.prakash.2018.326">Prakash et al 2018</a>, <a class="bk_pop" href="#hgps.REF.olsen.2023.1782">Olsen et al 2023</a>]. Sequential manifestations of cardiovascular decline include impaired relaxation of the heart muscle, followed by ventricular hypertrophy. This may occur in the setting of heart valve thickening or stenosis, or with hypertension that is often labile. Mitral and aortic valve abnormalities, including calcification, stenosis, and regurgitation, usually develop in the second decade of life. Aortic gradient increases exponentially with time at later stages of disease, portending critical aortic stenosis [<a class="bk_pop" href="#hgps.REF.gordon.2024.1356010">Gordon et al 2024</a>].</p><p>Systolic dysfunction is usually present in the setting of advanced disease, with or without identified coronary vascular insufficiency. Clinical symptoms of angina, dyspnea on exertion, or overt heart failure appear as late findings in the course of disease.</p><p>Transient ischemic attacks, silent strokes, or symptomatic strokes have occurred as early as age four years [<a class="bk_pop" href="#hgps.REF.silvera.2013.1091">Silvera et al 2013</a>]. Strokes can occur at any brain site, and therefore can lead to a variety of physical limitations and/or cognitive decline. Partial and complete carotid artery blockages can occur from plaque formation. The risk of cerebral infarction is around 32% by age 13.5 years, 20% of which are silent strokes.</p><p>Raynaud phenomenon in fingers occurs in a minority of affected individuals.</p><p>Without lonafarnib treatment, death typically occurs as a result of complications of cardiac or cerebrovascular disease. More than 80% of deaths are due to heart failure and/or myocardial infarction, most often between ages six and 20 years, with an average life span of approximately 14.5 years [<a class="bk_pop" href="#hgps.REF.gordon.2014.27">Gordon et al 2014</a>, <a class="bk_pop" href="#hgps.REF.gordon.2018a.982">Gordon et al 2018a</a>]. Average life span is extended to approximately 19 years with lonafarnib therapy, with similar causes of death.</p><p><b>Hearing.</b> Conductive hearing loss is highly prevalent at all ages, with low-frequency hearing loss more prevalent than high-frequency hearing loss [<a class="bk_pop" href="#hgps.REF.guardiani.2011.2250">Guardiani et al 2011</a>, <a class="bk_pop" href="#hgps.REF.gordon.2012.16666">Gordon et al 2012</a>].</p><p><b>Ophthalmologic.</b> Nocturnal lagophthalmos (the inability to fully close the eyes during sleep) is common. As a result, corneal dryness and clouding can occur. In a minority of individuals, corneal ulceration occurs due to exposure keratopathy [<a class="bk_pop" href="#hgps.REF.mantagos.2017.126">Mantagos et al 2017</a>].</p><p>
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<b>Other</b>
|
||
</p><ul><li class="half_rhythm"><div>Liver, kidney, gastrointestinal, neurologic, strength-for-size, and cognitive functions are normal.</div></li><li class="half_rhythm"><div>Tumor rate is not increased over that of the general population.</div></li><li class="half_rhythm"><div>Other changes associated with normal aging such as nearsightedness or farsightedness, arcus senilis, senile personality changes, or Alzheimer disease have not been documented.</div></li><li class="half_rhythm"><div>Children with HGPS appear to have a normal immune system; they respond as well as the general population when subjected to various infections. Wound healing is normal.</div></li></ul></div><div id="hgps.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><div id="hgps.T.classic_and_nonclassic_genotype_h" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Classic and Nonclassic Genotype HGPS: Causative <i>LMNA</i> Variants and Comparative Clinical Phenotypes</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1121/table/hgps.T.classic_and_nonclassic_genotype_h/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hgps.T.classic_and_nonclassic_genotype_h_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Genotype</th><th id="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>LMNA</i> Pathogenic Variant</th><th id="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Amino Acid <sup>1</sup></th><th id="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Phenotypic Features Compared to Classic HGPS <sup>2</sup></th><th id="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"># of Affected Persons Identified</th><th id="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_6" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference(s)</th></tr></thead><tbody><tr><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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||
<b>Classic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> HGPS</b>
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||
</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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||
<a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">c.1824C>T</a>
|
||
</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly608Gly</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 3.</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">214</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bk_pop" href="#hgps.REF.de_sandregiovannoli.2003.2055">De Sandre-Giovannoli et al [2003]</a>, <a class="bk_pop" href="#hgps.REF.eriksson.2003.293">Eriksson et al [2003]</a></td></tr><tr><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_1" rowspan="11" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Nonclassic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> HGPS</b>
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</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">c.1821G>A</a>
|
||
</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Val607Val</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe; neonatal progeria</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bk_pop" href="#hgps.REF.moulson.2007.882">Moulson et al [2007]</a>, <a class="bk_pop" href="#hgps.REF.reunert.2012.933">Reunert et al [2012]</a>, PRF</td></tr><tr><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">
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||
<u>c.1822G>A</u>
|
||
</a>
|
||
</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly608Ser</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Similar</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bk_pop" href="#hgps.REF.eriksson.2003.293">Eriksson et al [2003]</a>, PRF</td></tr><tr><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">c.1968G>A</a>
|
||
</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly656Gly</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Very mild</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bk_pop" href="#hgps.REF.hisama.2011.3002">Hisama et al [2011]</a>, <a class="bk_pop" href="#hgps.REF.barth_l_my.2015.1051">Barthélémy et al [2015]</a></td></tr><tr><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1968G>T</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly656His</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PRF</td></tr><tr><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">
|
||
<u>c.1968+1G>A</u>
|
||
</a>
|
||
</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bk_pop" href="#hgps.REF.navarro.2004.2493">Navarro et al [2004]</a>, <a class="bk_pop" href="#hgps.REF.moulson.2007.882">Moulson et al [2007]</a>, PRF</td></tr><tr><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">c.1968+1G>C</a>
|
||
</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bk_pop" href="#hgps.REF.iqbal.2008.266">Iqbal & Iftikhar [2008]</a>, PRF</td></tr><tr><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1968+1G>T</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Similar</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PRF</td></tr><tr><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">
|
||
<u>c.1968+2T>A</u>
|
||
</a>
|
||
</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bk_pop" href="#hgps.REF.bar.2017.212">Bar et al [2017]</a>, PRF</td></tr><tr><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">
|
||
<u>c.1968+2T>C</u>
|
||
</a>
|
||
</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PRF</td></tr><tr><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">c.1968+5G>A</a>
|
||
</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Very mild</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bk_pop" href="#hgps.REF.hisama.2011.3002">Hisama et al [2011]</a>, PRF</td></tr><tr><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">
|
||
<u>c.1968+5G>C</u>
|
||
</a>
|
||
</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Moderate</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3</td><td headers="hd_h_hgps.T.classic_and_nonclassic_genotype_h_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PRF</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">HGPS = Hutchinson-Gilford progeria syndrome; PRF = Progeria Research Foundation <a href="https://www.progeriaresearch.org/the-prf-diagnostic-testing-program/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Diagnostic Testing Program</a></p></div></dd><dt>1. </dt><dd><div id="hgps.TF.2.1"><p class="no_margin">Activation of the cryptic splice donor is not 100% efficient, so the amino acid change occurs in nonsynonymous variants in the proportion of the RNA that has followed the normal <a class="def" href="/books/n/gene/glossary/def-item/splicing/">splicing</a> pattern.</p></div></dd><dt>2. </dt><dd><div id="hgps.TF.2.2"><p class="no_margin">There is a spectrum of severity for classic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> HGPS, and most individuals with nonclassic genotype HGPS fall within that spectrum. Comparisons with classic genotype HGPS are based on the midrange of severity for classic genotype HGPS. Note that it is possible for a listed <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> to yield a spectrum of disease severity among different affected individuals.</p></div></dd><dt>3. </dt><dd><div id="hgps.TF.2.3"><p class="no_margin">Individuals with <i>LMNA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> <a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object" rid-ob="figobhgpsTlmnapathogenicvariantsreferenc">c.1824C>T</a> appear remarkably similar in <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> [<a class="bk_pop" href="#hgps.REF.eriksson.2003.293">Eriksson et al 2003</a>].</p></div></dd></dl></div></div></div></div><div id="hgps.Penetrance"><h3>Penetrance</h3><p>Penetrance is complete.</p></div><div id="hgps.Nomenclature"><h3>Nomenclature</h3><p>HGPS is also referred to as the Hutchinson-Gilford syndrome or progeria.</p></div><div id="hgps.Prevalence"><h3>Prevalence</h3><p>HGPS is an ultra-rare disease. The prevalence of children with HGPS per total population is one in 20 million living individuals, with an estimated 400 affected individuals worldwide [<a class="bk_pop" href="#hgps.REF.gordon.2014.27">Gordon et al 2014</a>].</p><p>The estimated birth incidence for HGPS is one in four million births, with no observed differences based on sex or ethnic background [<a class="bk_pop" href="#hgps.REF.hennekam.2006.2603">Hennekam 2006</a>].</p></div></div><div id="hgps.Genetically_Related_Allelic_Disorde"><h2 id="_hgps_Genetically_Related_Allelic_Disorde_">Genetically Related (Allelic) Disorders</h2><p>Many distinguishably different genetic conditions with nucleotide variants in <i>LMNA</i> have been identified.</p><p><b>Non-progerin-producing progeroid laminopathy</b> describes phenotypes that overlap with classic and nonclassic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> Hutchinson-Gilford progeria syndrome but are obviously different. Various pathogenic variants in <i>LMNA</i> identified through the Progeria Research Foundation's <a href="https://www.progeriaresearch.org/the-prf-diagnostic-testing-program/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Diagnostic Testing Program</a>, <a href="https://www.progeriaresearch.org/international-registry-2/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">International Progeria Patient Registry</a>, and/or <a href="https://www.progeriaresearch.org/medical-database/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Medical Database</a> result in a variety of lamin A abnormalities that cause various phenotypes.</p><p>Selected non-progeroid laminopathies caused by pathogenic <i>LMNA</i> variants that result in abnormal lamin A protein are listed in <a href="/books/NBK1121/table/hgps.T.lmna_allelic_disorders_nonprogero/?report=objectonly" target="object" rid-ob="figobhgpsTlmnaallelicdisordersnonprogero">Table 3</a>.</p><div id="hgps.T.lmna_allelic_disorders_nonprogero" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p><i>LMNA</i> Allelic Disorders (Non-Progeroid Laminopathies)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1121/table/hgps.T.lmna_allelic_disorders_nonprogero/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hgps.T.lmna_allelic_disorders_nonprogero_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System</th><th id="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Selected Disorders <sup>1</sup></th><th id="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th></tr></thead><tbody><tr><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_1" rowspan="4" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Striated muscle</b>
|
||
</td><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Congenital muscular dystrophy, <i>LMNA</i>-related (OMIM <a href="https://omim.org/entry/613205" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">613205</a>)</td><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td></tr><tr><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/edmd/">Emery-Dreifuss muscular dystrophy</a>
|
||
</td><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR</td></tr><tr><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Limb-girdle muscular dystrophy 1B (See Emery-Dreifuss Muscular Dystrophy, <a href="/books/n/gene/edmd/#edmd.Genetically_Related_Allelic_Disorde">Genetically Related Disorders</a>.)</td><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td></tr><tr><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/dcm-lmna/"><i>LMNA</i>-related dilated cardiomyopathy</a>
|
||
</td><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td></tr><tr><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Peripheral nerves</b>
|
||
</td><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Charcot-Marie-Tooth type 2B1 (see <a href="/books/n/gene/cmt/">Charcot-Marie-Tooth Hereditary Neuropathy Overview</a>)</td><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Fatty tissues</b>
|
||
</td><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dunnigan-type <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> partial lipodystrophy (OMIM <a href="https://omim.org/entry/151660" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">151660</a>)</td><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td></tr><tr><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_1" rowspan="3" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Several tissues</b>
|
||
</td><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardiomyopathy & brachydactyly, <i>LMNA-</i>related (heart-hand syndrome type IV) (OMIM <a href="https://omim.org/entry/610140" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">610140</a>)</td><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td></tr><tr><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Mandibuloacral dysplasia, <i>LMNA-</i>related <sup>2</sup> (OMIM <a href="https://omim.org/entry/248370" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">248370</a>)</td><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Restrictive dermopathy 2 (OMIM <a href="https://omim.org/entry/619793" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">619793</a>)</td><td headers="hd_h_hgps.T.lmna_allelic_disorders_nonprogero_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a>; AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a></p></div></dd><dt>1. </dt><dd><div id="hgps.TF.3.1"><p class="no_margin">See also OMIM <a href="https://omim.org/entry/150330" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">150330</a>.</p></div></dd><dt>2. </dt><dd><div id="hgps.TF.3.2"><p class="no_margin">Some features of premature aging are seen in <i>LMNA-</i>related mandibuloacral dysplasia.</p></div></dd></dl></div></div></div></div><div id="hgps.Differential_Diagnosis"><h2 id="_hgps_Differential_Diagnosis_">Differential Diagnosis</h2><p><b>Progeroid syndromes.</b> Other syndromes of known genetic cause that include some features of premature aging are listed in <a href="/books/NBK1121/table/hgps.T.progeroid_syndromes_in_the_differ/?report=objectonly" target="object" rid-ob="figobhgpsTprogeroidsyndromesinthediffer">Table 4</a>.</p><div id="hgps.T.progeroid_syndromes_in_the_differ" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Progeroid Syndromes in the Differential Diagnosis of Hutchinson-Gilford Progeria Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1121/table/hgps.T.progeroid_syndromes_in_the_differ/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hgps.T.progeroid_syndromes_in_the_differ_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Category</th><th id="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th></tr></thead><tbody><tr><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_1" rowspan="2" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Non-progerin-producing progeroid laminopathies</b>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>LMNA</i>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mandibuloacral dysplasia, <i>LMNA</i>-related (OMIM <a href="https://omim.org/entry/248370" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">248370</a>)</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>ZMPSTE24</i>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mandibuloacral dysplasia, <i>ZMPSTE24</i>-related (OMIM <a href="https://omim.org/entry/608612" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">608612</a>)</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_1" rowspan="11" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Non-laminopathy progeroid syndromes</b>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>AGPAT2</i>
|
||
<br />
|
||
<i>BSCL2</i>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/bscl/">Berardinelli-Seip congenital lipodystrophy</a> (<a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> generalized lipodystrophy)</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>B3GALT6</i>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Spondylodysplastic Ehlers-Danlos syndrome (spEDS-<i>B3GALT6</i>) (OMIM <a href="https://omim.org/entry/615349" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">615349</a>)</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>B4GALT7</i>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Spondylodysplastic Ehlers-Danlos syndrome (spEDS-<i>B4GALT7</i>) (OMIM <a href="https://omim.org/entry/130070" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">130070</a>)</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>BANF1</i>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nestor-Guillermo syndrome (OMIM <a href="https://omim.org/entry/614008" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">614008</a>)</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>ERCC6</i>
|
||
<br />
|
||
<i>ERCC8</i>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/cockayne/">Cockayne syndrome</a>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>GORAB</i>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gerodermia osteodysplastica (OMIM <a href="https://omim.org/entry/231070" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">231070</a>)</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>PDGFRB</i>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Penttinen syndrome (OMIM <a href="https://omim.org/entry/601812" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">601812</a>)</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td></tr><tr><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>POLR3A</i>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>POLR3A</i>-related Wiedemann-Rautenstrauch syndrome <sup>2</sup> (See <a href="/books/n/gene/pol3-leuk/">POLR3-Related Leukodystrophy</a>.)</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>PYCR1</i>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>PYCR1</i>-related Wiedemann-Rautenstrauch-like syndrome <sup>3</sup></td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>SLC25A24</i>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/slc25a24-fps/"><i>SLC25A24</i> Fontaine progeroid syndrome</a>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td></tr><tr><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>WRN</i>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/werner/">Werner syndrome</a>
|
||
</td><td headers="hd_h_hgps.T.progeroid_syndromes_in_the_differ_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a>; AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a></p></div></dd><dt>1. </dt><dd><div id="hgps.TF.4.1"><p class="no_margin">Biallelic pathogenic variants in <i>ZMPSTE24</i>, which encodes an enzyme involved in the post-translational processing of <i>LMNA</i>, can cause excess prelamin A proteins and the non-progerin-producing progeroid laminopathy <i>ZMPSTE24</i>-related mandibuloacral dysplasia.</p></div></dd><dt>2. </dt><dd><div id="hgps.TF.4.2"><p class="no_margin">
|
||
<a class="bk_pop" href="#hgps.REF.wambach.2018.968">Wambach et al [2018]</a>
|
||
</p></div></dd><dt>3. </dt><dd><div id="hgps.TF.4.3"><p class="no_margin">
|
||
<a class="bk_pop" href="#hgps.REF.lessel.2018.921">Lessel et al [2018]</a>
|
||
</p></div></dd></dl></div></div></div><p><b>Syndromes of unknown genetic cause</b> that include some features of premature aging include acrogeria (OMIM <a href="https://omim.org/entry/201200" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">201200</a>) and Hallermann-Streiff syndrome (OMIM <a href="https://omim.org/entry/234100" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">234100</a>).</p></div><div id="hgps.Management"><h2 id="_hgps_Management_">Management</h2><p>Comprehensive clinical practice guidelines for Hutchinson-Gilford progeria syndrome (HGPS) have been published (see <a href="https://www.progeriaresearch.org/patient-care-and-handbook/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Progeria Research Foundation</a>.)</p><div id="hgps.Evaluations_Following_Initial_Diagn"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with HGPS, the evaluations summarized in <a href="/books/NBK1121/table/hgps.T.hutchinsongilford_progeria_syndro/?report=objectonly" target="object" rid-ob="figobhgpsThutchinsongilfordprogeriasyndro">Table 5</a> (if not performed as part of the evaluation that led to diagnosis) are recommended.</p><div id="hgps.T.hutchinsongilford_progeria_syndro" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Hutchinson-Gilford Progeria Syndrome: Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1121/table/hgps.T.hutchinsongilford_progeria_syndro/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hgps.T.hutchinsongilford_progeria_syndro_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Growth/Feeding/Nutrition</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Weight & height plotted on standard growth charts to evaluate growth over time</div></li><li class="half_rhythm"><div>Nutritional assessment</div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Affected persons usually have caloric intake sufficient for growth, which is governed by pathobiology. Thus, ↑ caloric intake does not influence growth deficiency.</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dental</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dental exam & radiographs when needed</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Upon initial dental eruption</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skin/Hair</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of skin & hair manifestations</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Musculoskeletal</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Orthopedic eval for progressive coxa valga &/or avascular necrosis</div></li><li class="half_rhythm"><div>DXA scan to assess bone mineral density <sup>1</sup></div></li><li class="half_rhythm"><div>Skeletal radiographs to evaluate for acroosteolysis, clavicular resorption, coxa valga, & extraskeletal soft tissue calcifications</div></li><li class="half_rhythm"><div>OT & PT assessments, incl 6-minute walk test, goniometry to assess joint mobility, & assessment of ADL</div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiovascular</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>EKG</div></li><li class="half_rhythm"><div>Echocardiogram</div></li><li class="half_rhythm"><div>Carotid artery duplex scans to evaluate size of lumen & intimal thickness to establish baseline vascular status</div></li><li class="half_rhythm"><div>MRI/MRA of brain & neck</div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiologic eval</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for low-frequency conductive hearing loss</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Eyes</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for exposure keratopathy, corneal dryness, clouding, or ulceration</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic counseling</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>2</sup></td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To obtain a <a class="def" href="/books/n/gene/glossary/def-item/pedigree/">pedigree</a> & inform affected persons & their families re nature, MOI, & implications of HGPS to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family support</b>
|
||
<br />
|
||
<b>& resources</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By clinicians, wider care team, & family support organizations</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of family & social structure to determine need for:
|
||
<ul><li class="half_rhythm"><div>Community or <a href="#hgps.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a></div></li><li class="half_rhythm"><div>Social work involvement for parental support</div></li><li class="half_rhythm"><div>Home nursing referral</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ADL = activities of daily living; DXA = dual-energy x-ray absorptiometry; HGPS = Hutchinson-Gilford progeria syndrome; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; OT = occupational therapy; PT = physical therapy</p></div></dd><dt>1. </dt><dd><div id="hgps.TF.5.1"><p class="no_margin">This must be normalized for height age [<a class="bk_pop" href="#hgps.REF.gordon.2011.1670">Gordon et al 2011</a>].</p></div></dd><dt>1. </dt><dd><div id="hgps.TF.5.1_1"><p class="no_margin">Clinical geneticist, certified genetic counselor, certified genetic nurse, genetics advanced practice provider (nurse practitioner or physician assistant)</p></div></dd></dl></div></div></div></div><div id="hgps.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div id="hgps.Targeted_Therapy"><h4>Targeted Therapy</h4><p>
|
||
<i>In GeneReviews, a targeted therapy is one that addresses the specific underlying mechanism of disease causation (regardless of whether the therapy is significantly efficacious for one or more manifestation of the genetic condition); would otherwise not be considered without knowledge of the underlying genetic cause of the condition; or could lead to a cure</i>. —ED</p><p><b>Lonafarnib</b> (Zokinvy<sup>®</sup>) is a farnesyltransferase inhibitor. It is the only United States Food and Drug Administration (FDA)-approved therapy for HGPS. Its target action is inhibition of post-translational farnesylation of progerin, the active disease-causing protein in HGPS. Lonafarnib is an oral medication administered twice daily at an initial dose of 115 mg/m<sup>2</sup> followed by 150 mg/m<sup>2</sup> after four months of therapy. Toxicities (with suggested treatments) are mainly diarrhea (loperamide), gastrointestinal upset, nausea (ondansetron), and loss of appetite (cyproheptadine), which usually wane after a few months of therapy. Clinical trial results for lonafarnib have revealed improvement in vascular distensibility as measured via pulse wave velocity and vascular echodensity, increased bone rigidity, improved neurosensory hearing [<a class="bk_pop" href="#hgps.REF.gordon.2012.16666">Gordon et al 2012</a>], decreased headaches [<a class="bk_pop" href="#hgps.REF.ullrich.2013.427">Ullrich et al 2013</a>], and increased life span by 4.2 years on average (~30%) [<a class="bk_pop" href="#hgps.REF.gordon.2014.27">Gordon et al 2014</a>, <a class="bk_pop" href="#hgps.REF.gordon.2023.1734">Gordon et al 2023</a>]. For those too young to swallow capsules, administration in specific foods or ORA-Blend<sup>®</sup> is possible. Lonafarnib is approved by the FDA, European Medicines Agency (European Union), and Pharmaceuticals and Medical Devices Agency (Japan), and is available in other countries through managed access programs. It is also being administered as a monotherapy as a clinical trial extension (<a href="https://clinicaltrials.gov/study/NCT02579044" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCT02579044</a>).</p></div><div id="hgps.Supportive_Care"><h4>Supportive Care</h4><p>Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see <a href="/books/NBK1121/table/hgps.T.hutchinsongilford_progeria_syndro_1/?report=objectonly" target="object" rid-ob="figobhgpsThutchinsongilfordprogeriasyndro1">Table 6</a>).</p><div id="hgps.T.hutchinsongilford_progeria_syndro_1" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Hutchinson-Gilford Progeria Syndrome: Treatment of Manifestations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1121/table/hgps.T.hutchinsongilford_progeria_syndro_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hgps.T.hutchinsongilford_progeria_syndro_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" rowspan="3" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Growth deficiency</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Frequent small meals to maximize caloric intake</div></li><li class="half_rhythm"><div>Daily multivitamin</div></li><li class="half_rhythm"><div>Medication dosages should be based on body weight or body surface area & not on age. Anesthetics should be used w/particular caution.</div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Calcium supplementation is not recommended, due to potential for aggravating extraskeletal calcification formation & hypothetically aggravating vascular plaque status. Maintenance of normal calcium levels from dietary sources is encouraged.</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Podiatric eval & treatment to determine if shoe inserts are needed</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lack of body fat leads to foot discomfort</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">School adaptations as needed for short stature</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>General anesthesia precautions</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">General anesthesia & intubation should be performed w/extreme caution, ideally w/fiberoptic intubation.</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Persons w/HGPS have retrognathia, stiffened laryngeal structures, & a narrow & unusually shaped airway; additionally, they may exhibit an extreme sensitivity to alterations in blood pressure due to vascular stiffness.</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dental</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Fluoride supplement in areas where the water supply does not contain fluoride</div></li><li class="half_rhythm"><div>Extraction of primary teeth may be required to avoid dental crowding.</div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Since secondary teeth may erupt slowly or not at all, pulling primary teeth to make room for secondary teeth should be performed after secondary teeth have fully or almost fully erupted or descended.</div></li><li class="half_rhythm"><div>Once the primary tooth has been extracted, the secondary tooth often moves into the appropriate position w/time.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skin</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Use of sunscreen on all exposed areas of skin, incl the head, for outdoor activities</div></li><li class="half_rhythm"><div>Encourage sun-protective clothing incl hat</div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hip dislocation</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Conservative mgmt w/PT & body bracing when possible</div></li><li class="half_rhythm"><div>Surgical correction if essential, w/special attention to intubation & anesthesia guidelines</div></li><li class="half_rhythm"><div>Reconstructive hip surgery can be performed for repeated dislocations causing pain & significant decrease in quality of life.</div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgery should be treated as a substantial risk for stroke &/or cardiac events.</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Mildly low bone density</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Routine treatment for bone fractures</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Fracture rate & healing is similar to general pediatric population.</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Joint stiffness</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>PT/OT to maintain range of motion in large & small joints</div></li><li class="half_rhythm"><div>Active stretching & strengthening</div></li><li class="half_rhythm"><div>Hydrotherapy</div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="https://www.progeriaresearch.org/assets/files/pdf/Physical%20Therapy%2807-04%29.pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Physical Therapy and Occupational Therapy in Progeria</a>.</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Endocrine</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In females w/dysfunctional vaginal bleeding or spotting, short-term (i.e., 3-6 mos) low-dose combined oral contraceptives can be helpful to stabilize endometrium.</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" rowspan="4" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiovascular (CV) disease</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Healthy diet</div></li><li class="half_rhythm"><div>Maintain regular physical activity as tolerated.</div></li><li class="half_rhythm"><div>Maintain optimal hydration esp during hot weather & airplane travel.</div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Physical activity should account for limitations related to restricted joint mobility & hip problems incl osteoarthritis & hip dislocation.</div></li><li class="half_rhythm"><div>As the vasculature becomes less pliable & risk of CV disease ↑ over time, adequate oral hydration is esp important.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consider low-dose aspirin (2-3 mg/kg body weight) per day. <sup>1</sup></td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Based on evidence from adult studies that low-dose aspirin may prevent heart attacks & strokes.</div></li><li class="half_rhythm"><div>Anticoagulants other than aspirin may be warranted if vascular blockage, transient ischemic attacks, stroke, angina, or myocardial infarction occur.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Nitroglycerin is frequently of benefit if angina develops.</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Routine anti-congestive therapy is appropriate if congestive heart failure is present.</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Critical aortic stenosis</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>Treatment options:</b>
|
||
<ul><li class="half_rhythm"><div>Modified transcatheter aortic valve replacement (TAVR)</div></li><li class="half_rhythm"><div>Modified apico-aortic valve placement (AAC)</div></li></ul>
|
||
These are high-risk interventions that can improve cardiac status, quality of life, & increase life span.</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">When peak aortic gradient ≥20 mm Hg, frequent echocardiography should be initiated because aortic gradient increases exponentially. Late accelerated progression of aortic stenosis permits only a small window for optimizing risk-to-benefit ratio before failure ensues. Peak aortic gradients ~80-90 mm Hg warrant intervention. <sup>2</sup></td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hyperlipidemia</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Exercise, diet modification, & statin therapy as needed</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Lipid levels are typically normal.</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing loss</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Sitting at the front of the classroom can be helpful.</div></li><li class="half_rhythm"><div>Hearing aids as needed</div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Low-frequency conductive hearing loss often does not interfere w/ADL.</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Ophthalmologic</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Exposure keratitis can be treated during daytime w/ocular lubrication & during sleep w/moisturizing ointment or by closing eyelids w/skin tape.</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family/Community</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ensure appropriate social work involvement to connect families w/local resources, respite, & support.</div></li><li class="half_rhythm"><div>Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.</div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ongoing assessment of need for palliative care involvement &/or home nursing</div></li><li class="half_rhythm"><div>Consider involvement in adaptive sports.</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ADL = activities of daily living; HGPS = Hutchinson-Gilford progeria syndrome; OT = occupational therapy; PT = physical therapy</p></div></dd><dt>1. </dt><dd><div id="hgps.TF.6.1"><p class="no_margin">If chicken pox or influenza is prevalent in the community, consider discontinuing the aspirin during that time because of the increased risk of Reye syndrome.</p></div></dd><dt>2. </dt><dd><div id="hgps.TF.6.2"><p class="no_margin">To date, two persons have undergone modified TAVR; one was successfully treated and the other experienced intra- & perisurgical cardiac death [<a class="bk_pop" href="#hgps.REF.musumeci.2020.e365">Musumeci et al 2020</a>; L Gordon et al, unpublished data]. Four persons have undergone modified AAC surgery; two had successful >2-year follow ups, one died prior to two years after surgery, and one died within weeks of surgery [<a class="bk_pop" href="#hgps.REF.hoganson.2023.1292">Hoganson et al 2023</a>; <a class="bk_pop" href="#hgps.REF.gordon.2024.1356010">Gordon et al 2024</a>; L Gordon, unpublished data].</p></div></dd></dl></div></div></div></div></div><div id="hgps.Surveillance"><h3>Surveillance</h3><p>To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in <a href="/books/NBK1121/table/hgps.T.hutchinsongilford_progeria_syndro_2/?report=objectonly" target="object" rid-ob="figobhgpsThutchinsongilfordprogeriasyndro2">Table 7</a> are recommended.</p><div id="hgps.T.hutchinsongilford_progeria_syndro_2" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Hutchinson-Gilford Progeria Syndrome: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1121/table/hgps.T.hutchinsongilford_progeria_syndro_2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hgps.T.hutchinsongilford_progeria_syndro_2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Growth/Nutrition</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of growth & caloric intake</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">At each visit</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dental</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dental exam, radiographs, & cleaning</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Annually</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skin</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of skin manifestations</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">At each visit</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Musculoskeletal</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Orthopedic eval for avascular necrosis of hip, progressive coxa valga, & hip dislocation w/radiographs as needed</div></li><li class="half_rhythm"><div>OT & PT assessments incl 6-minute walk test, goniometry to assess joint mobility, & assessment of ADL</div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Endocrine</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of pubertal development</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit throughout adolescence</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_1" rowspan="2" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiovascular disease</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Blood pressure measurement w/appropriately sized cuff</div></li><li class="half_rhythm"><div>EKG</div></li><li class="half_rhythm"><div>Echocardiogram</div></li><li class="half_rhythm"><div>Carotid duplex scan <sup>1</sup></div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 6-12 mos</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Lipid profile</div></li><li class="half_rhythm"><div>Neurologic assessment for headaches & manifestations of stroke</div></li><li class="half_rhythm"><div>Head & neck MRI/MRA to assess for vascular changes & silent strokes</div></li></ul>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_3" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Ophthalmologic involvement</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Eval by ophthalmologist for exposure keratopathy, corneal dryness, clouding, or ulceration</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiology eval w/special attention to low-frequency conductive hearing loss</td></tr><tr><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family/Community</b>
|
||
</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Assessment of family need for social work support (e.g., palliative/respite care, home nursing, other local resources), care coordination, or follow-up <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> if new questions arise (e.g., family planning)</td><td headers="hd_h_hgps.T.hutchinsongilford_progeria_syndro_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ADL = activities of daily living; OT = occupational therapy; PT = physical therapy</p></div></dd><dt>1. </dt><dd><div id="hgps.TF.7.1"><p class="no_margin">Children may experience severe carotid artery atherosclerotic blockage prior to any significant EKG changes.</p></div></dd></dl></div></div></div></div><div id="hgps.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Children should avoid being in the midst of large crowds with much taller and larger peers because of the increased risk of injury.</p><p>Physical activity should be self-limited. Avoid uneven surfaces that could aggravate hip dysplasia, such as trampolines and bouncy houses. Avoid being carried by underage peers.</p><p>Avoid dehydration due to increased risk of stroke.</p><p>Avoid anemia and high fever, particularly in individuals with advanced cardiovascular disease.</p><p>Avoid calcium supplementation, due to the potential for aggravating extraskeletal calcification formation and hypothetically aggravating vascular plaque status.</p></div><div id="hgps.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#hgps.Prenatal_Testing_and_Preimplantatio">Genetic Counseling</a> for issues related to testing of at-risk relatives for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> purposes.</p></div><div id="hgps.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search HGPS or progeria within <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for information on clinical trials for HGPS.</p><p>A clinical treatment trial administering lonafarnib monotherapy (see <a href="#hgps.Targeted_Therapy">Targeted Therapy</a>) is ongoing as an extension of <a href="https://clinicaltrials.gov/study/NCT02579044" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCT02579044</a>.</p><p>A clinical treatment trial administering progerinin, an oral small molecule inhibitor of progerin / lamin A binding, is currently being conducted [<a class="bk_pop" href="#hgps.REF.kang.2021.5">Kang et al 2021</a>, <a class="bk_pop" href="#hgps.REF.kang.2023.1232">Kang et al 2023</a>] (<a href="https://clinicaltrials.gov/study/NCT06775041" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCT06775041</a>).</p><p>A clinical treatment trial administering lonafarnib (see <a href="#hgps.Targeted_Therapy">Targeted Therapy</a>) plus <a href="https://www.clinicaltrials.gov/study/NCT02579044" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">everolimus combination therapy</a> has been completed and results are pending (<a href="https://clinicaltrials.gov/study/NCT02579044" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCT02579044</a>). Everolimus is a rapalog (rapamycin-like drug) mTOR inhibitor that increases cellular autophagy. It is an oral medication administered once daily. Everolimus is approved as a medication to treat non-HGPS conditions. Rapamycin improved cellular phenotypes in HGPS fibroblasts via increased autophagy [<a class="bk_pop" href="#hgps.REF.cao.2011.2833">Cao et al 2011</a>, <a class="bk_pop" href="#hgps.REF.cenni.2011.e36">Cenni et al 2011</a>] and extends life span in a lamin A-deficient mouse model.</p><p>A clinical treatment trial administering lonafarnib in combination with pravastatin and zoledronate demonstrated evidence of increased bone mineral density but no other improvements over that of lonafarnib monotherapy [<a class="bk_pop" href="#hgps.REF.gordon.2016.114">Gordon et al 2016</a>]. Extraskeletal calcifications of <a class="def" href="/books/n/gene/glossary/def-item/unknown-significance/">unknown significance</a> increased with treatment [<a class="bk_pop" href="#hgps.REF.gordon.2019.103">Gordon et al 2019</a>]. Since rate of bone fracture is normal in individuals with HGPS, this combination therapy was not recommended.</p></div></div><div id="hgps.Genetic_Counseling"><h2 id="_hgps_Genetic_Counseling_">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>. —ED.</p><div id="hgps.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Hutchinson-Gilford progeria syndrome (HGPS) is an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> disorder typically caused by a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div id="hgps.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>Ninety-eight percent of individuals reported to date with HGPS whose parents have undergone <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> have the disorder as the result of a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div><ul><li class="half_rhythm"><div>The parental origin of the <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>
|
||
<i>LMNA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> was paternal in four of the four families included in one study [<a class="bk_pop" href="#hgps.REF.eriksson.2003.293">Eriksson et al 2003</a>].</div></li><li class="half_rhythm"><div>A study of paternal age effect found that on average the father's age was significantly increased by about five years [<a class="bk_pop" href="#hgps.REF.brown.1985.375">Brown et al 1985</a>].</div></li></ul></li><li class="half_rhythm"><div>Approximately 2% of currently living individuals with the classic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> HGPS identified through the Progeria Research Foundation <a href="https://www.progeriaresearch.org/the-prf-diagnostic-testing-program/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Diagnostic Testing Program</a> have HGPS as the result of an <i>LMNA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> inherited from an unaffected parent with presumed gonadal (or somatic and gonadal) <a class="def" href="/books/n/gene/glossary/def-item/mosaicism/">mosaicism</a>. Maternal somatic and <a class="def" href="/books/n/gene/glossary/def-item/gonadal-mosaicism/">gonadal mosaicism</a> was demonstrated in one family [<a class="bk_pop" href="#hgps.REF.wuyts.2005.66">Wuyts et al 2005</a>].</div></li><li class="half_rhythm"><div>Parents of individuals with HGPS are not affected.</div></li></ul><p>
|
||
<b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>The risk to the sibs of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> depends on the genetic status of the proband's parents. Because HGPS is typically caused by a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> (i.e., neither parent of the proband has the <i>LMNA</i> pathogenic variant), the <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> to the sibs of a proband is low but not zero due to the possibility of parental <a class="def" href="/books/n/gene/glossary/def-item/gonadal-mosaicism/">gonadal mosaicism</a>.</div></li><li class="half_rhythm"><div>Of the 214 known individuals with classic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> HGPS in the Progeria Research Foundation <a href="https://www.progeriaresearch.org/international-registry-2/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">International Progeria Patient Registry</a>, four (2%) instances of non-twin sib recurrence have been reported to date. The number of unaffected sibs among the 214 total individuals is unknown. Thus, the <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> for subsequent pregnancies after one individual has been genetically diagnosed with HGPS is low but significantly higher than the one in four million incidence for the general population.</div></li></ul><p><b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Individuals with classic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> HGPS are not known to reproduce; there is one individual with nonclassic genotype HGPS and a mild <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> who is known to have reproduced [<a class="bk_pop" href="#hgps.REF.hisama.2011.3002">Hisama et al 2011</a>].</p></div><div id="hgps.Prenatal_Testing_and_Preimplantatio"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>LMNA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been identified in an affected family member, <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> for a pregnancy at increased risk (because of the rare possibility of <a class="def" href="/books/n/gene/glossary/def-item/gonadal-mosaicism/">gonadal mosaicism</a> in a parent) and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a>. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="hgps.Resources"><h2 id="_hgps_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/">here</a>.</i></p>
|
||
<ul><li class="half_rhythm"><div>
|
||
<b>MedlinePlus</b>
|
||
</div><div>
|
||
<a href="https://medlineplus.gov/genetics/condition/hutchinson-gilford-progeria-syndrome/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Hutchinson-Gilford progeria syndrome</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>National Organization for Rare Disorders (NORD)</b>
|
||
</div><div>Patient Information and Assistance Programs</div><div>
|
||
<a href="https://rarediseases.org/rare-diseases/hutchinson-gilford-progeria/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Hutchinson-Gilford Progeria Syndrome</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Progeria Clinical Care Handbook</b>
|
||
</div><div>
|
||
<a href="https://www.progeriaresearch.org/patient-care-and-handbook/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">progeriaresearch.org/patient-care-and-handbook</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>The Progeria Research Foundation</b>
|
||
</div><div><b>Phone:</b> 978-535-2594</div><div><b>Email:</b> info@progeriaresearch.org</div><div>
|
||
<a href="http://www.progeriaresearch.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">progeriaresearch.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>PRF International Progeria Patient Registry</b>
|
||
</div><div><b>Phone:</b> 978-535-2594</div><div><b>Fax:</b> 978-535-5849</div><div><b>Email:</b> info@progeriaresearch.org</div><div>
|
||
<a href="http://www.progeriaresearch.org/patient_registry.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">progeriaresearch.org/international-registry-2</a>
|
||
</div></li></ul>
|
||
</div><div id="hgps.Molecular_Genetics"><h2 id="_hgps_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div id="hgps.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Hutchinson-Gilford Progeria Syndrome: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1121/table/hgps.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hgps.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_hgps.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_hgps.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_hgps.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_hgps.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_hgps.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_hgps.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_hgps.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/4000" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>LMNA</i>
|
||
</a>
|
||
</td><td headers="hd_b_hgps.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=4000" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">1q22</a>
|
||
</td><td headers="hd_b_hgps.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/P02545" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Prelamin-A<wbr style="display:inline-block"></wbr>/C</a>
|
||
</td><td headers="hd_b_hgps.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://databases.lovd.nl/shared/genes/LMNA" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">LMNA homepage - Leiden Muscular Dystrophy pages</a>
|
||
</td><td headers="hd_b_hgps.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=LMNA" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">LMNA</a>
|
||
</td><td headers="hd_b_hgps.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=LMNA[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">LMNA</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="hgps.TFA.1"><p class="no_margin">Data are compiled from the following standard references: <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
<a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="hgps.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Hutchinson-Gilford Progeria Syndrome (<a href="/omim/150330,176670" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1121/table/hgps.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hgps.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/150330" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">150330</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LAMIN A/C; LMNA</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/176670" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">176670</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS</td></tr></tbody></table></div></div><div id="hgps.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>The nuclear lamina is a protein-containing layer attached to the inner nuclear membrane. It is composed of a family of polypeptides, with the major components being the lamins A, B1, B2, and C. Lamins A and C are formed by alternative <a class="def" href="/books/n/gene/glossary/def-item/splicing/">splicing</a> of the <i>LMNA</i>/<i>C</i> <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> transcript. Splicing within <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 10 gives rise to lamin C, whereas transcription of all 12 exons gives rise to lamin A. Lamins B1 and B2 are encoded by separate genes, and there are no known progeroid pathogenic variants within lamins B1 and B2.</p><p>Lamin A is normally synthesized as a precursor molecule (prelamin A) and undergoes four major post-translational processing steps. First, because prelamin A contains a CAAX (cysteine / aliphatic / aliphatic / any amino acid) box at its carboxyl terminus, it is modified by farnesylation. Following farnesylation, cleavage of the last three amino acids, <a class="def" href="/books/n/gene/glossary/def-item/methylation/">methylation</a> of the C terminus, and internal proteolytic cleavage by the ZMPSTE24 protease occurs. Removal of the last 15 coding amino acids along with the CAAX box and farnesyl group generates mature lamin A with 646 amino acids.</p><p>The classic <i>LMNA</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> c.1824C>T activates a cryptic <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> in <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 11, resulting in a protein with a 50-amino acid <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> near its C-terminal end. The deletion removes the recognition site that normally leads to ZMPSTE24 proteolytic cleavage of the terminal 18 amino acids of prelamin A, along with the phosphorylation site(s) involved in the dissociation and reassociation of the nuclear membrane at each cell division. The resulting protein, progerin, is shortened and permanently farnesylated. The lipophilic farnesyl moiety is utilized to zip code prelamin (and hence progerin) into the inner nuclear membrane, but the hydrophobic tail is then normally removed, allowing mature lamin A to move freely in the nuclear scaffold. The lack of farnesyl cleavage for progerin likely results in long-term association with the inner nuclear membrane, where it exerts progressively more damage to cells as they go through repeated mitoses. That the failure to remove the farnesyl group is at least in part responsible for the phenotypes observed in HGPS is strongly supported by studies on both cell and mouse models that have either been engineered to produce a non-farnesylated progerin product or treated with a drug that inhibits farnesylation, rendering a non-farnesylated progerin product.</p><p>Other <i>LMNA</i> pathogenic variants that do not result in the production of progerin result in lamin A with abnormal structure and/or function (including abnormal interactions with the nuclear membrane lamin-associated proteins).</p><p><b>Mechanism of disease causation.</b> Gain of abnormal function</p><p><b><i>LMNA</i>-specific laboratory technical considerations.</b>
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<i>LMNA</i> pathogenic variants c.1821G>A, c.1822G>A, c.1824C>T, c.1968G>A, and c.1968G>T cause disease by affecting <i>LMNA</i> <a class="def" href="/books/n/gene/glossary/def-item/splicing/">splicing</a>. Pathogenic variants c.1822G>A and c.1968G>T also result in an amino acid change for the fraction of the RNA that does not use the cryptic <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> (see <a href="/books/NBK1121/table/hgps.T.classic_and_nonclassic_genotype_h/?report=objectonly" target="object" rid-ob="figobhgpsTclassicandnonclassicgenotypeh">Table 2</a>).</p><div id="hgps.T.lmna_pathogenic_variants_referenc" class="table"><h3><span class="label">Table 9. </span></h3><div class="caption"><p><i>LMNA</i> Pathogenic Variants Referenced in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1121/table/hgps.T.lmna_pathogenic_variants_referenc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hgps.T.lmna_pathogenic_variants_referenc_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_1" rowspan="4" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nucleotide/153281093" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_170707<wbr style="display:inline-block"></wbr>.2</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/27436946" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_733821<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1821G>A <sup>1</sup></td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 1.</td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_4" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="/books/NBK1121/table/hgps.T.classic_and_nonclassic_genotype_h/?report=objectonly" target="object" rid-ob="figobhgpsTclassicandnonclassicgenotypeh">Table 2</a>.</td></tr><tr><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1822G>A <sup>1</sup></td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly608Ser <sup>1</sup></td></tr><tr><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1824C>T <sup>1</sup></td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 1.</td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assoc w/classic <a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> HGPS</td></tr><tr><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1968G>A <sup>2</sup></td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly656His <sup>2</sup></td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_4" rowspan="7" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="/books/NBK1121/table/hgps.T.classic_and_nonclassic_genotype_h/?report=objectonly" target="object" rid-ob="figobhgpsTclassicandnonclassicgenotypeh">Table 2</a>.</td></tr><tr><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_1" rowspan="6" scope="rowgroup" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nucleotide/153281093" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_170707<wbr style="display:inline-block"></wbr>.2</a>
|
||
</td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1968+1G>A</td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td></tr><tr><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1968+1G>C</td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td></tr><tr><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1968+2T>A</td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td></tr><tr><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1968+2T>C</td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td></tr><tr><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1968+5G>A</td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td></tr><tr><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1968+5G>C</td><td headers="hd_h_hgps.T.lmna_pathogenic_variants_referenc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>.hgvs.org</a>). See <a href="/books/n/gene/app3/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd><dt>1. </dt><dd><div id="hgps.TF.9.1"><p class="no_margin">Pathogenic variant results in activation of a cryptic <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a>.</p></div></dd><dt>2. </dt><dd><div id="hgps.TF.9.2"><p class="no_margin">The nucleotide substitution affects the donor <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> of <a class="def" href="/books/n/gene/glossary/def-item/intron/">intron</a> 11.</p></div></dd></dl></div></div></div></div></div><div id="hgps.Chapter_Notes"><h2 id="_hgps_Chapter_Notes_">Chapter Notes</h2><div id="hgps.Author_Notes"><h3>Author Notes</h3><p>Dr Gordon is an investigator for progeria clinical treatment trials being conducted at Boston Children's Hospital. She leads the Progeria Research Foundation's International Progeria Patient Registry and Diagnostic Testing Program. She is interested in hearing from patients, patient families, and clinicians with questions about progeria or patients with suspected progeria. She is also interested in hearing from families or clinicians who are considering treatment with lonafarnib. For more information, contact Dr Gordon at <a href="mailto:dev@null" data-email="gro.hcraeserairegorp@nodrogl" class="oemail">gro.hcraeserairegorp@nodrogl</a>.</p><p><b>Sentynl Therapeutics</b><br />Zokinvy<sup>®</sup> Information and Registration<br /><a href="http://www.zokinvy.com" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.zokinvy.com</a></p></div><div id="hgps.Acknowledgments"><h3>Acknowledgments</h3><p>We are grateful to all those with progeria and their families who have contributed to the medical and research progress on progeria. We thank the Progeria Research Foundation and the Boston Children's Hospital progeria clinical trial team members for advancing progeria natural history studies, treatments, and clinical care.</p></div><div id="hgps.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>13 March 2025 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>17 January 2019 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>8 January 2015 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>6 January 2011 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>10 August 2006 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>12 December 2003 (me) Review posted live</div></li><li class="half_rhythm"><div>31 July 2003 (wtb) Original submission</div></li></ul></div></div><div id="hgps.References"><h2 id="_hgps_References_">References</h2><div id="hgps.Published_Guidelines__Consensus_Sta"><h3>Published Guidelines / Consensus Statements</h3><ul class="simple-list"><li class="half_rhythm"><div>Progeria Research Foundation. The Progeria Handbook: A Guide for Families & Health Care Providers of Children with Progeria. Includes genetic testing guidelines. Available <a href="https://www.progeriaresearch.org/assets/files/PRFhandbook_0410.pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">online</a> (pdf). Accessed 2-12-25.</div></li></ul></div><div id="hgps.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="hgps.REF.bar.2017.212">Bar
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[<a href="/pmc/articles/PMC3421121/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3421121</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22419169" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22419169</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="hgps.REF.silvera.2013.1091">Silvera
|
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VM, Gordon
|
||
LB, Orbach
|
||
DB, Campbell
|
||
SE, Machan
|
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JT, Ullrich
|
||
NJ. Imaging characteristics of cerebrovascular arteriopathy and stroke in Hutchinson-Gilford progeria syndrome.
|
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AJNR Am J Neuroradiol.
|
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2013;34:1091-7.
|
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[<a href="/pmc/articles/PMC7964639/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7964639</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23179651" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23179651</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="hgps.REF.ullrich.2013.427">Ullrich
|
||
NJ, Kieran
|
||
MW, Miller
|
||
DT, Gordon
|
||
LB, Cho
|
||
YJ, Silvera
|
||
VM, Giobbie-Hurder
|
||
A, Neuberg
|
||
D, Kleinman
|
||
ME. Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment.
|
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Neurology.
|
||
2013;81:427-30.
|
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[<a href="/pmc/articles/PMC3776537/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3776537</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23897869" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23897869</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="hgps.REF.wambach.2018.968">Wambach
|
||
JA, Wegner
|
||
DJ, Patni
|
||
N, Kircher
|
||
M, Willing
|
||
MC, Baldridge
|
||
D, Xing
|
||
C, Agarwal
|
||
AK, Vergano
|
||
SAS, Patel
|
||
C, Grange
|
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DK, Kenney
|
||
A, Najaf
|
||
T, Nickerson
|
||
DA, Bamshad
|
||
MJ, Cole
|
||
FS, Garg
|
||
A. Bi-allelic POLR3A loss-of-function variants cause autosomal-recessive Wiedemann–Rautenstrauch syndrome.
|
||
Am J Hum Genet.
|
||
2018;103:968-75.
|
||
[<a href="/pmc/articles/PMC6288318/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6288318</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30414627" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30414627</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="hgps.REF.wuyts.2005.66">Wuyts
|
||
W, Biervliet
|
||
M, Reyniers
|
||
E, D'Apice
|
||
MR, Novelli
|
||
G, Storm
|
||
K. Somatic and gonadal mosaicism in Hutchinson-Gilford progeria.
|
||
Am J Med Genet A.
|
||
2005;135:66-8.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/15793835" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15793835</span></a>]</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK1121/?report=reader">PubReader</a></li><li><a href="/books/NBK1121/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK1121" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK1121" style="display:none" title="Cite this Page"><div class="bk_tt">Gordon LB, Brown WT, Collins FS. Hutchinson-Gilford Progeria Syndrome. 2003 Dec 12 [Updated 2025 Mar 13]. 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