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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>ADCY5 Dyskinesia - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
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<meta name="citation_title" content="ADCY5 Dyskinesia">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2020/07/30">
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<meta name="citation_author" content="Fuki M Hisama">
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<meta name="citation_author" content="Jennifer Friedman">
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<meta name="citation_author" content="Wendy H Raskind">
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<meta name="citation_author" content="Thomas D Bird">
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<meta name="citation_keywords" content="Adenylate cyclase type 5">
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<meta name="citation_keywords" content="ADCY5">
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<meta name="citation_keywords" content="ADCY5 Dyskinesia">
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<meta name="DC.Title" content="ADCY5 Dyskinesia">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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<meta name="DC.Contributor" content="Fuki M Hisama">
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<meta name="DC.Contributor" content="Jennifer Friedman">
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<meta name="DC.Contributor" content="Wendy H Raskind">
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<meta name="DC.Contributor" content="Thomas D Bird">
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<meta name="DC.Date" content="2020/07/30">
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<meta name="description" content="ADCY5 dyskinesia is a hyperkinetic movement disorder (more prominent in the face and arms than the legs) characterized by infantile to late-adolescent onset of chorea, athetosis, dystonia, myoclonus, or a combination of these. To date, affected individuals have had overlapping (but not identical) manifestations with wide-ranging severity. The facial movements are typically periorbital and perioral. The dyskinesia is prone to episodic or paroxysmal exacerbation lasting minutes to hours, and may occur during sleep. Precipitating factors in some persons have included emotional stress, intercurrent illness, sneezing, or caffeine; in others, no precipitating factors have been identified. In some children, severe infantile axial hypotonia results in gross motor delays accompanied by chorea, sometimes with language delays. The overall tendency is for the abnormal movements to stabilize in early middle age, at which point they may improve in some individuals; less commonly, the abnormal movements are slowly progressive, increasing in severity and frequency.">
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<meta name="og:title" content="ADCY5 Dyskinesia">
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<meta name="og:description" content="ADCY5 dyskinesia is a hyperkinetic movement disorder (more prominent in the face and arms than the legs) characterized by infantile to late-adolescent onset of chorea, athetosis, dystonia, myoclonus, or a combination of these. To date, affected individuals have had overlapping (but not identical) manifestations with wide-ranging severity. The facial movements are typically periorbital and perioral. The dyskinesia is prone to episodic or paroxysmal exacerbation lasting minutes to hours, and may occur during sleep. Precipitating factors in some persons have included emotional stress, intercurrent illness, sneezing, or caffeine; in others, no precipitating factors have been identified. In some children, severe infantile axial hypotonia results in gross motor delays accompanied by chorea, sometimes with language delays. The overall tendency is for the abnormal movements to stabilize in early middle age, at which point they may improve in some individuals; less commonly, the abnormal movements are slowly progressive, increasing in severity and frequency.">
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class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK263441_"><span class="title" itemprop="name"><i>ADCY5</i> Dyskinesia</span></h1><p class="contribs">Hisama FM, Friedman J, Raskind WH, et al.</p><p class="fm-aai"><a href="#_NBK263441_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 25 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="adcy5-dysk.Summary" itemprop="description"><h2 id="_adcy5-dysk_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>ADCY5</i> dyskinesia is a hyperkinetic movement disorder (more prominent in the face and arms than the legs) characterized by infantile to late-adolescent onset of chorea, athetosis, dystonia, myoclonus, or a combination of these. To date, affected individuals have had overlapping (but not identical) manifestations with wide-ranging severity. The facial movements are typically periorbital and perioral. The dyskinesia is prone to episodic or paroxysmal exacerbation lasting minutes to hours, and may occur during sleep. Precipitating factors in some persons have included emotional stress, intercurrent illness, sneezing, or caffeine; in others, no precipitating factors have been identified. In some children, severe infantile axial hypotonia results in gross motor delays accompanied by chorea, sometimes with language delays. The overall tendency is for the abnormal movements to stabilize in early middle age, at which point they may improve in some individuals; less commonly, the abnormal movements are slowly progressive, increasing in severity and frequency.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>ADCY5</i> dyskinesia is established in a proband with a hyperkinetic movement disorder (in the absence of structural brain abnormalities) and a heterozygous pathogenic or likely pathogenic variant (or, rarely, biallelic pathogenic or likely pathogenic variants) in <i>ADCY5</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Management by multidisciplinary specialists, including a neurologist or neurogeneticist, cardiologist, physical therapist, social worker, speech and language pathologist, and other specialists is recommended as needed. Anecdotally, medications have had variable effect in suppressing debilitating symptoms. Treatment should be determined by the individual's physician, taking into account potential risk/benefit, other medical conditions, allergies, and potential drug-drug interactions. Response to medication is difficult to evaluate because some individuals have long periods (weeks) of remission of the dyskinesia. Physical and occupational therapy may help maintain mobility and function. Speech and language therapy for dysarthria may include alternative communication methods. Cognitive impairment and psychiatric manifestations are managed per standard practice.</p><p><i>Surveillance:</i> Routine follow up of neurologic involvement, dysarthria, oculomotor involvement, musculoskeletal involvement, activities of daily living, cognitive impairment, and psychiatric manifestations.</p><p><i>Pregnancy management:</i> Potential teratogenic effects of medications given for treatment of <i>ADCY5</i> dyskinesia should be discussed with affected women of childbearing age, ideally prior to conception.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>ADCY5</i> dyskinesia is typically inherited in an autosomal dominant (AD) manner. Autosomal recessive (AR) inheritance has been reported in two families.</p><p><b>AD inheritance.</b> The majority of individuals diagnosed with <i>ADCY5</i> dyskinesia represent simplex cases (i.e., a single affected family member) and have the disorder as the result of a <i>de novo</i> pathogenic variant. Each child of an individual with <i>ADCY5</i> dyskinesia has a 50% chance of inheriting the pathogenic variant.</p><p><b>Both AD and AR inheritance.</b> Once the <i>ADCY5</i> pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for <i>ADCY5</i> dyskinesia are possible.</p></div></div><div id="adcy5-dysk.Diagnosis"><h2 id="_adcy5-dysk_Diagnosis_">Diagnosis</h2><p>No consensus diagnostic guidelines for <i>ADCY5</i> dyskinesia have been published.</p><div id="adcy5-dysk.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Diagnosis of <i>ADCY5</i> dyskinesia <b>should be suspected</b> in individuals with the following clinical findings, neuroimaging, and family history.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Infantile to late-adolescent onset of choreiform, myoclonic, and/or dystonic movements that involve the limbs, neck, and/or face</div></li><li class="half_rhythm"><div>Familial benign chorea</div></li><li class="half_rhythm"><div>Alternating hemiplegia in childhood</div></li><li class="half_rhythm"><div>Myoclonus-dystonia</div></li><li class="half_rhythm"><div>Focal dystonia and tremor</div></li><li class="half_rhythm"><div>Spasticity and dystonia</div></li><li class="half_rhythm"><div>Sleep-related motor and behavior disorder</div></li></ul><p><b>Neuroimaging.</b> Brain MRI shows no evidence of structural abnormalities.</p><p><b>Family history</b> is consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations) or, rarely, autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.</p></div><div id="adcy5-dysk.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>ADCY5</i> dyskinesia <b>is established</b> in a proband with a hyperkinetic movement disorder (in the absence of structural brain abnormalities) and a heterozygous pathogenic or likely pathogenic variant (or, rarely, biallelic pathogenic or likely pathogenic variants) in <i>ADCY5</i> identified by molecular genetic testing (see <a href="/books/NBK263441/table/adcy5-dysk.T.molecular_genetic_testing_u/?report=objectonly" target="object" rid-ob="figobadcy5dyskTmoleculargenetictestingu">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [<a class="bibr" href="#adcy5-dysk.REF.richards.2015.405" rid="adcy5-dysk.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of a heterozygous <i>ADCY5</i> variant(s) of uncertain significance does not establish or rule out the diagnosis of this disorder.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single-gene testing and multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, exome array, genome sequencing) depending on the phenotype.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in <a href="#adcy5-dysk.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#adcy5-dysk.Option_1">Option 1</a>), whereas those in whom the diagnosis of <i>ADCY5</i> dyskinesia has not been considered are more likely to be diagnosed using genomic testing (see <a href="#adcy5-dysk.Option_2">Option 2</a>).</p><div id="adcy5-dysk.Option_1"><h4>Option 1</h4><p><b>Single-gene testing.</b> Sequence analysis of <i>ADCY5</i> is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected.</p><p>If no variant is detected by the sequencing method used, the next step typically is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications; however, because <i>ADCY5</i> dyskinesia occurs through a gain-of-function mechanism and large intragenic deletion or duplication has not been reported, testing for intragenic deletions or duplication is unlikely to identify a disease-causing variant.</p><p>Mosaicism of pathogenic variants has been reported.</p><p><b>A movement disorder</b>
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<b>multigene panel</b> that includes <i>ADCY5</i> and other genes of interest (see <a href="#adcy5-dysk.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="adcy5-dysk.Option_2"><h4>Option 2</h4><p><b>Comprehensive</b>
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<b>genomic testing</b> does not require the clinician to determine which gene(s) are likely involved. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figadcy5dyskTmoleculargenetictestingu"><a href="/books/NBK263441/table/adcy5-dysk.T.molecular_genetic_testing_u/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobadcy5dyskTmoleculargenetictestingu"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="adcy5-dysk.T.molecular_genetic_testing_u"><a href="/books/NBK263441/table/adcy5-dysk.T.molecular_genetic_testing_u/?report=objectonly" target="object" rid-ob="figobadcy5dyskTmoleculargenetictestingu">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>ADCY5</i> Dyskinesia </p></div></div></div></div></div><div id="adcy5-dysk.Clinical_Characteristics"><h2 id="_adcy5-dysk_Clinical_Characteristics_">Clinical Characteristics</h2><div id="adcy5-dysk.Clinical_Description"><h3>Clinical Description</h3><p>The hallmark of <i>ADCY5</i> dyskinesia is infantile to late-adolescent onset of a hyperkinetic movement disorder characterized by chorea, athetosis, dystonia, myoclonus, or a combination which tends to be more prominent in the face and arms than the legs [<a class="bibr" href="#adcy5-dysk.REF.chen.2015.2026" rid="adcy5-dysk.REF.chen.2015.2026">Chen et al 2015</a>]. Affected individuals identified to date have overlapping but not identical clinical manifestations with wide-ranging clinical severity. The facial movements are typically periorbital and perioral. The dyskinesia is prone to episodic or paroxysmal bouts of exacerbation lasting minutes to hours, and may occur during sleep. Precipitating factors have included emotional stress, intercurrent illness, sneezing, or caffeine [<a class="bibr" href="#adcy5-dysk.REF.vijiaratnam.2019.512" rid="adcy5-dysk.REF.vijiaratnam.2019.512">Vijiaratnam et al 2019</a>]. In other affected individuals, no precipitating factors have been identified. In some children, severe infantile axial hypotonia results in gross motor delays accompanied by chorea, sometimes with language delays [<a class="bibr" href="#adcy5-dysk.REF.carecchio.2017.37" rid="adcy5-dysk.REF.carecchio.2017.37">Carecchio et al 2017</a>]. The phenotypic spectrum of this disorder is still being elucidated.</p><p><i>ADCY</i> dyskinesia was first identified in a single multigenerational family [<a class="bibr" href="#adcy5-dysk.REF.chen.2012.630" rid="adcy5-dysk.REF.chen.2012.630">Chen et al 2012</a>]. Following that publication, more than 40 individuals representing simplex cases (i.e., a single occurrence in a family) and members of more than ten families with <i>ADCY5</i> dyskinesia have been reported [<a class="bibr" href="#adcy5-dysk.REF.chen.2015.2026" rid="adcy5-dysk.REF.chen.2015.2026">Chen et al 2015</a>, <a class="bibr" href="#adcy5-dysk.REF.vijiaratnam.2019.512" rid="adcy5-dysk.REF.vijiaratnam.2019.512">Vijiaratnam et al 2019</a>]. The following description of the phenotypic features associated with this condition is based on these reports.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figadcy5dyskTadcy5dyskinesiafrequency"><a href="/books/NBK263441/table/adcy5-dysk.T.adcy5_dyskinesia_frequency/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobadcy5dyskTadcy5dyskinesiafrequency"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="adcy5-dysk.T.adcy5_dyskinesia_frequency"><a href="/books/NBK263441/table/adcy5-dysk.T.adcy5_dyskinesia_frequency/?report=objectonly" target="object" rid-ob="figobadcy5dyskTadcy5dyskinesiafrequency">Table 2. </a></h4><p class="float-caption no_bottom_margin"><i>ADCY5</i> Dyskinesia: Frequency of Select Features </p></div></div><div id="adcy5-dysk.Neurologic_Manifestations"><h4>Neurologic Manifestations</h4><p>All affected individuals reported to date have had episodes of choreiform, myoclonic, and/or dystonic movements that primarily affect the limbs, face, and/or neck. Typically the abnormal movements first appear during infancy, childhood, or early adolescence (range: neonatal period to age 19 years) [<a class="bibr" href="#adcy5-dysk.REF.chen.2015.2026" rid="adcy5-dysk.REF.chen.2015.2026">Chen et al 2015</a>].</p><p>In those with milder manifestations, the abnormal movements involve the face and distal limbs (although minimally affecting function) and are socially debilitating. Some affected individuals may be described as "excessively clumsy."</p><p>In more severely affected infants, the earliest manifestations can include severe axial hypotonia resulting in developmental delays that lead to impairment in the ability to ambulate, requiring use of wheelchairs.</p><p>The abnormal movements are continual during waking hours, and have been noted to persist during sleep, particularly in infancy. Several affected individuals have noted severe, sleep-disrupting movements [<a class="bibr" href="#adcy5-dysk.REF.chen.2014.542" rid="adcy5-dysk.REF.chen.2014.542">Chen et al 2014</a>, <a class="bibr" href="#adcy5-dysk.REF.chen.2015.2026" rid="adcy5-dysk.REF.chen.2015.2026">Chen et al 2015</a>] that occurred during stages N2 and N3 of sleep, and were not associated with epileptiform discharges in one individual [<a class="bibr" href="#adcy5-dysk.REF.chen.2014.542" rid="adcy5-dysk.REF.chen.2014.542">Chen et al 2014</a>].</p><p>A curious feature observed in some individuals is the occurrence of long periods (days to weeks) of remission.</p><p>The movements are often exacerbated by anxiety or stress and with drowsiness or sleep (although not by startle or alcohol). Less common triggers include intercurrent illness, fatigue, excitement, or caffeine, although one individual showed improvement with caffeine and other individuals have reported benefit [J Friedman, personal observation]. One woman reported that her choreiform movements were precipitated by enforced inactivity (e.g., as during a road trip), and could often be alleviated by voluntary movement.</p><p>Facial "twitches" (previously thought to be myokymia) involving the periorbital and/or perioral muscles may also be present. Twitches were also documented in limb muscles in one individual [<a class="bibr" href="#adcy5-dysk.REF.fernandez.2001.486" rid="adcy5-dysk.REF.fernandez.2001.486">Fernandez et al 2001</a>].</p><p>Dysarthria and hypotonia have been reported in some affected individuals [<a class="bibr" href="#adcy5-dysk.REF.chen.2014.542" rid="adcy5-dysk.REF.chen.2014.542">Chen et al 2014</a>, <a class="bibr" href="#adcy5-dysk.REF.chen.2015.2026" rid="adcy5-dysk.REF.chen.2015.2026">Chen et al 2015</a>, <a class="bibr" href="#adcy5-dysk.REF.mencacci.2015.80" rid="adcy5-dysk.REF.mencacci.2015.80">Mencacci et al 2015</a>].</p><p>Intellect and life span are usually normal. In severely affected individuals with onset in early childhood, intellectual disability may be present.</p><p>Neurologic examination can vary widely between individuals and in the same individual over time. Examination may reveal:</p><ul><li class="half_rhythm"><div>A mixed movement disorder that may include prominent choreiform movements usually affecting the hands and/or feet, often characterized as piano playing movements [<a class="bibr" href="#adcy5-dysk.REF.vijiaratnam.2019.512" rid="adcy5-dysk.REF.vijiaratnam.2019.512">Vijiaratnam et al 2019</a>];</div></li><li class="half_rhythm"><div>Myoclonic and dystonic movements [<a class="bibr" href="#adcy5-dysk.REF.friedman.2016.147" rid="adcy5-dysk.REF.friedman.2016.147">Friedman et al 2016</a>];</div></li><li class="half_rhythm"><div>Non-myokymic facial twitching, hyperreflexia of the lower limbs, and intermittent head or limb tremors [<a class="bibr" href="#adcy5-dysk.REF.chen.2014.542" rid="adcy5-dysk.REF.chen.2014.542">Chen et al 2014</a>];</div></li><li class="half_rhythm"><div>Axial hypotonia with limb and axial weakness including severe neck weakness [<a class="bibr" href="#adcy5-dysk.REF.chen.2014.542" rid="adcy5-dysk.REF.chen.2014.542">Chen et al 2014</a>, <a class="bibr" href="#adcy5-dysk.REF.chen.2015.2026" rid="adcy5-dysk.REF.chen.2015.2026">Chen et al 2015</a>];</div></li><li class="half_rhythm"><div>Alternating hemiplegia of childhood [<a class="bibr" href="#adcy5-dysk.REF.westenberger.2017.306" rid="adcy5-dysk.REF.westenberger.2017.306">Westenberger et al 2017</a>];</div></li><li class="half_rhythm"><div>Progressive spasticity and dystonia with hyperreflexia [<a class="bibr" href="#adcy5-dysk.REF.dean.2019.510" rid="adcy5-dysk.REF.dean.2019.510">Dean et al 2019</a>, <a class="bibr" href="#adcy5-dysk.REF.waalkens.2018.e214" rid="adcy5-dysk.REF.waalkens.2018.e214">Waalkens et al 2018</a>].</div></li></ul><p><b>Somatic mosaicism</b> has been demonstrated in 43% of individuals with a <i>de novo</i> pathogenic variant [<a class="bibr" href="#adcy5-dysk.REF.raskind.2017.305" rid="adcy5-dysk.REF.raskind.2017.305">Raskind et al 2017</a>] and in the founders of two multigenerational families, including one individual shown to be mosaic for the <a href="/books/NBK263441/table/adcy5-dysk.T.notable_adcy5_pathogenic_va/?report=objectonly" target="object" rid-ob="figobadcy5dyskTnotableadcy5pathogenicva">p.Met1029Lys</a> variant who demonstrated considerable improvement during adulthood [<a class="bibr" href="#adcy5-dysk.REF.chen.2015.2026" rid="adcy5-dysk.REF.chen.2015.2026">Chen et al 2015</a>].</p><p>Another individual, thought to be mosaic for <a href="/books/NBK263441/table/adcy5-dysk.T.notable_adcy5_pathogenic_va/?report=objectonly" target="object" rid-ob="figobadcy5dyskTnotableadcy5pathogenicva">p.Arg418Trp</a>, exhibited significantly milder phenotypic features: fewer facial twitches, milder chorea, and no dysarthria [<a class="bibr" href="#adcy5-dysk.REF.mencacci.2015.80" rid="adcy5-dysk.REF.mencacci.2015.80">Mencacci et al 2015</a>].</p><p>The natural history varies. In most, the abnormal movements are static or slowly progressive with increased severity and frequency. In some instances, choreiform movements have been more constant, and less paroxysmal, from the onset [<a class="bibr" href="#adcy5-dysk.REF.mencacci.2015.80" rid="adcy5-dysk.REF.mencacci.2015.80">Mencacci et al 2015</a>]. The overall tendency is for the abnormal movements to stabilize in early middle age, at which point they may improve in some individuals.</p></div><div id="adcy5-dysk.Cardiac_Complications"><h4>Cardiac Complications</h4><p><a class="bibr" href="#adcy5-dysk.REF.chen.2011.1252" rid="adcy5-dysk.REF.chen.2011.1252">Chen et al [2011]</a> reported that five individuals in a family with <i>ADCY5</i> dyskinesia also had congestive heart failure. Because <i>ADCY5</i> encodes a specific adenylyl cyclase that is highly expressed in both striatum and myocardium [<a class="bibr" href="#adcy5-dysk.REF.ho.2010.495" rid="adcy5-dysk.REF.ho.2010.495">Ho et al 2010</a>], these observations suggest that pathogenic variants in <i>ADCY5</i> could contribute to cardiac pathology; further study is required.</p></div><div id="adcy5-dysk.Studies"><h4>Studies</h4><p><b>Needle electromyogram (EMG) studies</b> in two individuals with facial muscle twitching suggested centrally driven irregular muscle movements that were also observed in other muscles, including the orbicularis oculi, tongue, frontalis, and dorsal interosseous muscles. No fibrillations, fasciculations, myokymia, or myotonia were noted on EMG.</p><p><b>Brain imaging (MRI, CT)</b> is normal.</p><p><b>Neuropathology.</b> Gross pathology is normal. Detailed immunohistochemical analysis in one individual with molecularly confirmed <i>ADCY5</i> dyskinesia revealed increased immunoreactivity for ADCY5 in multiple brain regions as well as tau deposits in deep cortical sulci, the midbrain and hippocampus. Lewy bodies and amyloid pathology were absent [<a class="bibr" href="#adcy5-dysk.REF.chen.2019.70" rid="adcy5-dysk.REF.chen.2019.70">Chen et al 2019</a>].</p></div></div><div id="adcy5-dysk.GenotypePhenotype_Correlation"><h3>Genotype-Phenotype Correlations</h3><p>In general, the number of individuals and families tested to date is too small to make reliable predictions of phenotypic features based on genotype; however, one missense variant, <a href="/books/NBK263441/table/adcy5-dysk.T.notable_adcy5_pathogenic_va/?report=objectonly" target="object" rid-ob="figobadcy5dyskTnotableadcy5pathogenicva">p.Ala726Thr</a>, has been associated with a milder phenotype [<a class="bibr" href="#adcy5-dysk.REF.vijiaratnam.2019.512" rid="adcy5-dysk.REF.vijiaratnam.2019.512">Vijiaratnam et al 2019</a>] (see <a href="/books/NBK263441/table/adcy5-dysk.T.notable_adcy5_pathogenic_va/?report=objectonly" target="object" rid-ob="figobadcy5dyskTnotableadcy5pathogenicva">Table 7</a>).</p></div><div id="adcy5-dysk.Penetrance"><h3>Penetrance</h3><p>In molecularly confirmed <i>ADCY5</i> dyskinesia, penetrance has been 100% in both men and women.</p></div><div id="adcy5-dysk.Nomenclature"><h3>Nomenclature</h3><p><i>ADCY5</i> dyskinesia has been previously described as:</p><ul><li class="half_rhythm"><div>A variant of familial essential ("benign") chorea. Although the term "benign" was used to distinguish the movement disorder from progressive, neurodegenerative forms of chorea such as <a href="/books/n/gene/huntington/?report=reader">Huntington disease</a>, <i>ADCY5</i> dyskinesia can be disabling and in some instances progressive, and, thus, use of the term "benign hereditary chorea" should be avoided.</div></li><li class="half_rhythm"><div>"Familial dyskinesia facial myokymia" because the prominent facial twitching was originally thought to be myokymia (see <a href="#adcy5-dysk.Clinical_Description">Clinical Description</a>); however, more recently EMG studies of affected individuals have revealed that these twitches are not myokymia.</div></li></ul><p>DYT-<i>ADCY5</i> may be an appropriate designation because dystonia is often a prominent feature [<a class="bibr" href="#adcy5-dysk.REF.marras.2012.1016" rid="adcy5-dysk.REF.marras.2012.1016">Marras et al 2012</a>].</p></div><div id="adcy5-dysk.Prevalence"><h3>Prevalence</h3><p>No data are available for the prevalence of <i>ADCY5</i> dyskinesia. It is likely underdiagnosed because of the variability in the clinical presentation and age of onset, and because of the high rate of <i>de novo</i> variants resulting in simplex cases (i.e., a single occurrence in a family) [<a class="bibr" href="#adcy5-dysk.REF.vijiaratnam.2019.512" rid="adcy5-dysk.REF.vijiaratnam.2019.512">Vijiaratnam et al 2019</a>].</p></div></div><div id="adcy5-dysk.Genetically_Related_Allelic_D"><h2 id="_adcy5-dysk_Genetically_Related_Allelic_D_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>ADCY5.</i></p></div><div id="adcy5-dysk.Differential_Diagnosis"><h2 id="_adcy5-dysk_Differential_Diagnosis_">Differential Diagnosis</h2><div id="adcy5-dysk.Hereditary_Disorders"><h3>Hereditary Disorders</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figadcy5dyskTgenesofinterestinthedi"><a href="/books/NBK263441/table/adcy5-dysk.T.genes_of_interest_in_the_di/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobadcy5dyskTgenesofinterestinthedi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="adcy5-dysk.T.genes_of_interest_in_the_di"><a href="/books/NBK263441/table/adcy5-dysk.T.genes_of_interest_in_the_di/?report=objectonly" target="object" rid-ob="figobadcy5dyskTgenesofinterestinthedi">Table 3. </a></h4><p class="float-caption no_bottom_margin">Genes of Interest in the Differential Diagnosis of <i>ADCY5</i> Dyskinesia </p></div></div><p><a href="/books/n/gene/mt-overview/?report=reader">Mitochondrial disorders</a> can present with dystonia or other abnormal movements.</p></div><div id="adcy5-dysk.DrugInduced_and_Acquired_Diso"><h3>Drug-Induced and Acquired Disorders</h3><p>Tardive dyskinesia, a hyperkinetic movement disorder associated with long-term use of specific dopamine receptor blocking agents (including neuroleptics and certain antiemetics) [<a class="bibr" href="#adcy5-dysk.REF.aquino.2014.s113" rid="adcy5-dysk.REF.aquino.2014.s113">Aquino & Lang 2014</a>], is often precipitated by a recent dose reduction or a change to a less potent drug.</p><p>Sydenham chorea, a manifestation of acute rheumatic fever, is the most common cause of acquired chorea in childhood, and typically presents between ages five and 12 years. Although carditis and arthritis are other manifestations of rheumatic fever, chorea may be the only clinical sign. Antistreptolysin O (ASO) titers are elevated in a significant proportion of affected individuals.</p><p>Multiple sclerosis can cause continuous facial myokymia in individuals with lesions impinging on the facial nerve as it courses in the dorsolateral pontine tegmentum. Other features – particularly abnormalities on brain MRI, which are disseminated in space and time – should assist in making the correct diagnosis.</p><p>Note: The hyperkinetic movements of <i>ADCY5</i> dyskinesia may be mistakenly thought to be epileptiform; however, normal EEGs, lack of impaired consciousness, and/or lack of response to antiepileptic medication distinguish epilepsy from <i>ADCY5</i> dyskinesia.</p></div></div><div id="adcy5-dysk.Management"><h2 id="_adcy5-dysk_Management_">Management</h2><p>Consensus clinical management recommendations for <i>ADCY5</i> dyskinesia have not been published.</p><div id="adcy5-dysk.Evaluations_Following_Initial"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>ADCY5</i> dyskinesia, the evaluations summarized in <a href="/books/NBK263441/table/adcy5-dysk.T.recommended_evaluations_fol/?report=objectonly" target="object" rid-ob="figobadcy5dyskTrecommendedevaluationsfol">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figadcy5dyskTrecommendedevaluationsfol"><a href="/books/NBK263441/table/adcy5-dysk.T.recommended_evaluations_fol/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobadcy5dyskTrecommendedevaluationsfol"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="adcy5-dysk.T.recommended_evaluations_fol"><a href="/books/NBK263441/table/adcy5-dysk.T.recommended_evaluations_fol/?report=objectonly" target="object" rid-ob="figobadcy5dyskTrecommendedevaluationsfol">Table 4. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with <i>ADCY5</i> Dyskinesia </p></div></div></div><div id="adcy5-dysk.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Management by multidisciplinary specialists, including a neurologist, or neurogeneticist, cardiologist, physical therapist, social worker, speech and language pathologist, and other specialists is recommended as needed.</p><p><b>Medication</b> has been variably effective in suppressing debilitating manifestations. Treatment should be determined by the individual's physician, taking into account potential risk/benefit, other medical conditions, allergies, and potential drug-drug interactions. Response to medication is difficult to evaluate in an individual because some have long periods (weeks) of remission of the dyskinesia [<a class="bibr" href="#adcy5-dysk.REF.vijiaratnam.2019.512" rid="adcy5-dysk.REF.vijiaratnam.2019.512">Vijiaratnam et al 2019</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figadcy5dyskTtreatmentofmanifestations"><a href="/books/NBK263441/table/adcy5-dysk.T.treatment_of_manifestations/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobadcy5dyskTtreatmentofmanifestations"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="adcy5-dysk.T.treatment_of_manifestations"><a href="/books/NBK263441/table/adcy5-dysk.T.treatment_of_manifestations/?report=objectonly" target="object" rid-ob="figobadcy5dyskTtreatmentofmanifestations">Table 5. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with <i>ADCY5</i> Dyskinesia </p></div></div><div id="adcy5-dysk.Developmental_Delay__Intellec"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:</p><ul><li class="half_rhythm"><div>Individualized education plan (IEP) services:</div><ul><li class="half_rhythm"><div>An IEP provides specially designed instruction and related services to children who qualify.</div></li><li class="half_rhythm"><div>IEP services will be reviewed annually to determine whether any changes are needed.</div></li><li class="half_rhythm"><div>Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.</div></li><li class="half_rhythm"><div>PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</div></li><li class="half_rhythm"><div>As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.</div></li></ul></li><li class="half_rhythm"><div>A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.</div></li><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></div></div><div id="adcy5-dysk.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figadcy5dyskTrecommendedsurveillancefo"><a href="/books/NBK263441/table/adcy5-dysk.T.recommended_surveillance_fo/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobadcy5dyskTrecommendedsurveillancefo"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="adcy5-dysk.T.recommended_surveillance_fo"><a href="/books/NBK263441/table/adcy5-dysk.T.recommended_surveillance_fo/?report=objectonly" target="object" rid-ob="figobadcy5dyskTrecommendedsurveillancefo">Table 6. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with <i>ADCY5</i> Dyskinesia </p></div></div></div><div id="adcy5-dysk.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>The only exacerbating factor that is observed consistently across affected individuals is the presence of anxiety and exposure to typical life stressors. Further investigation is needed to determine whether stress management techniques or limitation of stressful activities may reduce the number and frequency of movements.</p></div><div id="adcy5-dysk.Evaluation_of_Relatives_at_Ri"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#adcy5-dysk.Related_Genetic_Counseling_Is">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="adcy5-dysk.Pregnancy_Management"><h3>Pregnancy Management</h3><p>Potential teratogenic effects of medications given for treatment of <i>ADCY5</i> dyskinesia should be discussed with affected women of childbearing age, ideally prior to conception.</p><p>See <a href="https://www.mothertobaby.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MotherToBaby</a> for further information on medication use during pregnancy.</p></div><div id="adcy5-dysk.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <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 access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="adcy5-dysk.Genetic_Counseling"><h2 id="_adcy5-dysk_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="adcy5-dysk.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>ADCY5</i> dyskinesia is typically inherited in an autosomal dominant manner, often as the result of a <i>de novo</i> pathogenic variant. Autosomal recessive inheritance of <i>ADCY5</i> dyskinesia has been reported in two families [<a class="bibr" href="#adcy5-dysk.REF.barrett.2017.193" rid="adcy5-dysk.REF.barrett.2017.193">Barrett et al 2017</a>, <a class="bibr" href="#adcy5-dysk.REF.bohlega.2019.145" rid="adcy5-dysk.REF.bohlega.2019.145">Bohlega et al 2019</a>].</p></div><div id="adcy5-dysk.Autosomal_Dominant_Inheritanc"><h3>Autosomal Dominant Inheritance – Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>The majority of individuals diagnosed with <i>ADCY5</i> dyskinesia represent simplex cases (i.e., a single affected family member) and have the disorder as the result of a <i>de novo</i> pathogenic variant [<a class="bibr" href="#adcy5-dysk.REF.vijiaratnam.2019.512" rid="adcy5-dysk.REF.vijiaratnam.2019.512">Vijiaratnam et al 2019</a>].</div></li><li class="half_rhythm"><div>Some individuals diagnosed with <i>ADCY5</i> dyskinesia have the disorder as the result of a pathogenic variant inherited from a parent who may or may not have clinical manifestations of the disorder.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband to confirm their genetic status and to allow reliable recurrence risk counseling.</div></li><li class="half_rhythm"><div>If the pathogenic variant identified in the proband is not identified in either parent several possibilities should be considered:</div><ul><li class="half_rhythm"><div class="half_rhythm">The proband has a <i>de novo</i> pathogenic variant. In a high percentage of individuals with an <i>ADCY5</i>
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<i>de novo</i> pathogenic variant, mutation occurred in later stages of embryogenesis resulting in somatic mosaicism for that variant [<a class="bibr" href="#adcy5-dysk.REF.vijiaratnam.2019.512" rid="adcy5-dysk.REF.vijiaratnam.2019.512">Vijiaratnam et al 2019</a>] (Note: A pathogenic variant is reported as <i>de novo</i> if: (1) the pathogenic variant found in the proband is not detected in parental DNA; and (2) parental identity testing has confirmed biological maternity and paternity; if parental identity testing is not performed, the variant is reported as "assumed <i>de novo</i>" [<a class="bibr" href="#adcy5-dysk.REF.richards.2015.405" rid="adcy5-dysk.REF.richards.2015.405">Richards et al 2015</a>]).</div></li><li class="half_rhythm"><div class="half_rhythm">The proband inherited a pathogenic variant from a parent with germline (or somatic and germline) mosaicism [<a class="bibr" href="#adcy5-dysk.REF.vijiaratnam.2019.512" rid="adcy5-dysk.REF.vijiaratnam.2019.512">Vijiaratnam et al 2019</a>]. (Note: Testing of parental leukocyte DNA may not detect all instances of parental somatic mosaicism.)</div><div class="half_rhythm">A parent with somatic and germline mosaicism for an <i>ADCY5</i> pathogenic variant may be mildly/minimally affected [<a class="bibr" href="#adcy5-dysk.REF.chen.2015.2026" rid="adcy5-dysk.REF.chen.2015.2026">Chen et al 2015</a>].</div></li></ul></li><li class="half_rhythm"><div>The family history of some individuals diagnosed with <i>ADCY5</i> dyskinesia may appear to be negative because of failure to recognize the disorder in family members or mild/late onset of the disease in a heterozygous parent. Therefore, an apparently negative family history cannot be confirmed unless molecular genetic testing has established that neither parent is heterozygous for the pathogenic variant identified in the proband.</div></li></ul><p><b>Sibs of a proband.</b> The risk to the sibs of the proband depends on the genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If a parent of the proband is affected and/or is known to have the <i>ADCY5</i> pathogenic variant identified in the proband, the risk to sibs of inheriting the pathogenic variant is 50%. All sibs who inherit an <i>ADCY5</i> pathogenic variant will most likely have clinical manifestations of the disorder (see <a href="#adcy5-dysk.Penetrance">Penetrance</a>); however, the range of clinical manifestations may vary widely among heterozygous family members.</div></li><li class="half_rhythm"><div>If the <i>ADCY5</i> pathogenic variant identified in the proband cannot be detected in the leukocyte DNA of either parent (or the parents are clinically unaffected but their genetic status is unknown), the recurrence risk to sibs is greater than that of the general population because of the possibility of parental mosaicism (which has been documented in <i>ADCY5</i> dyskinesia) [<a class="bibr" href="#adcy5-dysk.REF.chen.2015.2026" rid="adcy5-dysk.REF.chen.2015.2026">Chen et al 2015</a>, <a class="bibr" href="#adcy5-dysk.REF.chen.2016" rid="adcy5-dysk.REF.chen.2016">Chen et al 2016</a>].</div></li></ul><p><b>Offspring of a proband.</b> Each child of an individual with <i>ADCY5</i> dyskinesia has a 50% chance of inheriting the pathogenic variant.</p><p><b>Other family members.</b> The risk to other family members depends on the status of the proband's parents: if a parent has the pathogenic variant, the parent's family members may be at risk.</p></div><div id="adcy5-dysk.Autosomal_Recessive_Inheritan"><h3>Autosomal Recessive Inheritance – Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>The parents of an affected child are obligate heterozygotes (i.e., presumed to be carriers of one <i>ADCY5</i> pathogenic variant based on family history).</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband to confirm that each parent is heterozygous for an <i>ADCY5</i> pathogenic variant and to allow reliable recurrence risk assessment. (<i>De novo</i> variants are known to occur at a low but appreciable rate in autosomal recessive disorders [<a class="bibr" href="#adcy5-dysk.REF.j_nsson.2017.519" rid="adcy5-dysk.REF.j_nsson.2017.519">Jónsson et al 2017</a>].)</div></li><li class="half_rhythm"><div>Individuals who are heterozygous for a pathogenic variant associated with autosomal recessive <i>ADCY5</i> dyskinesia are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
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<b>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for an <i>ADCY5</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Individuals who are heterozygous for a pathogenic variant associated with autosomal recessive <i>ADCY5</i> dyskinesia are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p><b>Offspring of a proband.</b> Unless an individual with <i>ADCY5</i> dyskinesia has children with an affected individual or a carrier, his/her offspring will be obligate heterozygotes (carriers) for a pathogenic variant in <i>ADCY5</i>.</p><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier of an <i>ADCY5</i> pathogenic variant.</p><div id="adcy5-dysk.Carrier_Detection"><h4>Carrier Detection</h4><p>Carrier testing for at-risk relatives requires prior identification of the <i>ADCY5</i> pathogenic variants in the family.</p></div></div><div id="adcy5-dysk.Related_Genetic_Counseling_Is"><h3>Related Genetic Counseling Issues</h3><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.</div></li></ul></div><div id="adcy5-dysk.Prenatal_Testing_and_Preimpla"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>ADCY5</i> pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for <i>ADCY5</i> dyskinesia are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="adcy5-dysk.Resources"><h2 id="_adcy5-dysk_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>ADCY5.ORG</b>
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</div><div><b>Phone:</b> 858-882-7280</div><div><b>Email:</b> info@adcy5.org</div><div>
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<a href="http://www.adcy5.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">adcy5.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Dystonia Medical Research Foundation</b>
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</div><div><b>Phone:</b> 312-755-0198</div><div><b>Email:</b> dystonia@dystonia-foundation.org</div><div>
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<a href="https://dystonia-foundation.org/what-is-dystonia/types-dystonia/paroxysmal/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Paroxysmal Dystonia & Dyskinesias</a>
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</div></li><li class="half_rhythm"><div>
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<b>MedlinePlus</b>
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</div><div>
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<a href="https://medlineplus.gov/genetics/condition/adcy5-related-dyskinesia/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ADCY5-related dyskinesia</a>
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</div></li></ul>
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</div><div id="adcy5-dysk.Molecular_Genetics"><h2 id="_adcy5-dysk_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 class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figadcy5dyskmolgenTA"><a href="/books/NBK263441/table/adcy5-dysk.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobadcy5dyskmolgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="adcy5-dysk.molgen.TA"><a href="/books/NBK263441/table/adcy5-dysk.molgen.TA/?report=objectonly" target="object" rid-ob="figobadcy5dyskmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">ADCY5 Dyskinesia: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figadcy5dyskmolgenTB"><a href="/books/NBK263441/table/adcy5-dysk.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobadcy5dyskmolgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="adcy5-dysk.molgen.TB"><a href="/books/NBK263441/table/adcy5-dysk.molgen.TB/?report=objectonly" target="object" rid-ob="figobadcy5dyskmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for ADCY5 Dyskinesia (View All in OMIM) </p></div></div><div id="adcy5-dysk.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>The adenylyl cyclase gene family encodes a number of proteins that convert adenosine triphosphate (ATP) to cyclic adenosine-3',5'-monophosphate (cAMP), a second messenger molecule that exerts a wide variety of effects via a number of intracellular signaling pathways [<a class="bibr" href="#adcy5-dysk.REF.halls.2017.171" rid="adcy5-dysk.REF.halls.2017.171">Halls & Cooper 2017</a>].</p><p><i>ADCY5</i> encodes adenylyl cyclase type V (ADCY5), one of nine different membrane-bound adenylyl cyclases. ADCY5 converts adenosine triphosphate (ATP) to cyclic adenosine-3',5'-monophosphate (cAMP). Stimulation of ADCY5 by β-adrenergic agonists through a G-protein-coupled receptor induces a conformational change, aligning the two cytoplasmic domains such that they form a catalytic pocket in which ATP can bind [<a class="bibr" href="#adcy5-dysk.REF.chen.2014.542" rid="adcy5-dysk.REF.chen.2014.542">Chen et al 2014</a>].</p><p>ADCY5 is highly expressed in striatum and myocardium. ADCY5 is especially prevalent in the nucleus accumbens, accounting for 80% of adenylate cyclase activation [<a class="bibr" href="#adcy5-dysk.REF.chen.2011.1252" rid="adcy5-dysk.REF.chen.2011.1252">Chen et al 2011</a>].</p><p><b>Mechanism of disease causation.</b> Gain-of-function missense pathogenic variants in <i>ADCY5</i> have been shown to increase intracellular cAMP, which could exert a myriad of effects at the cellular level [<a class="bibr" href="#adcy5-dysk.REF.chen.2014.542" rid="adcy5-dysk.REF.chen.2014.542">Chen et al 2014</a>]. Presumably, increased ADCY5 activity affects either the signal transduction pathway following β-adrenergic stimulation or the interaction of the protein with other regulatory molecules [<a class="bibr" href="#adcy5-dysk.REF.mencacci.2015.80" rid="adcy5-dysk.REF.mencacci.2015.80">Mencacci et al 2015</a>].</p><p>A loss-of-function (<a href="/books/NBK263441/table/adcy5-dysk.T.notable_adcy5_pathogenic_va/?report=objectonly" target="object" rid-ob="figobadcy5dyskTnotableadcy5pathogenicva">c.2088+1G>A</a>) variant has been identified in a single family with hyperkinetic movements [<a class="bibr" href="#adcy5-dysk.REF.carapito.2015.423" rid="adcy5-dysk.REF.carapito.2015.423">Carapito et al 2015</a>].</p><p>The mechanism by which contrasting gain of function and haploinsufficiency both result in a similar clinical presentation is currently unknown, but may result from the sum of ADCY effects on both stimulatory and inhibitory cellular pathways.</p><p>In mice, overexpression of ADCY5 leads to age-related cardiomyopathy and disruption protects against β-adrenergic-mediated cardiac stress [<a class="bibr" href="#adcy5-dysk.REF.ho.2010.495" rid="adcy5-dysk.REF.ho.2010.495">Ho et al 2010</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figadcy5dyskTnotableadcy5pathogenicva"><a href="/books/NBK263441/table/adcy5-dysk.T.notable_adcy5_pathogenic_va/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figobadcy5dyskTnotableadcy5pathogenicva"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="adcy5-dysk.T.notable_adcy5_pathogenic_va"><a href="/books/NBK263441/table/adcy5-dysk.T.notable_adcy5_pathogenic_va/?report=objectonly" target="object" rid-ob="figobadcy5dyskTnotableadcy5pathogenicva">Table 7. </a></h4><p class="float-caption no_bottom_margin">Notable <i>ADCY5</i> Pathogenic Variants </p></div></div></div></div><div id="adcy5-dysk.Chapter_Notes"><h2 id="_adcy5-dysk_Chapter_Notes_">Chapter Notes</h2><div id="adcy5-dysk.Author_History"><h3>Author History</h3><p>Thomas D Bird, MD (2014-present)<br />Jennifer Friedman, MD (2014-present)<br />Fuki M Hisama, MD (2014-present)<br />Wendy H Raskind, MD, PhD (2020-present)<br />Chris Shaw, BS; University of Washington (2014-2020)</p></div><div id="adcy5-dysk.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>30 July 2020 (bp) Comprehensive update posted live</div></li><li class="half_rhythm"><div>17 December 2015 (fh) Revision: addition of data from <a class="bibr" href="#adcy5-dysk.REF.chen.2015.2026" rid="adcy5-dysk.REF.chen.2015.2026">Chen et al [2015]</a> and <a class="bibr" href="#adcy5-dysk.REF.mencacci.2015.80" rid="adcy5-dysk.REF.mencacci.2015.80">Mencacci et al [2015]</a></div></li><li class="half_rhythm"><div>18 December 2014 (me) Review posted live</div></li><li class="half_rhythm"><div>29 August 2014 (fh) Original submission</div></li></ul></div></div><div id="adcy5-dysk.References"><h2 id="_adcy5-dysk_References_">References</h2><div id="adcy5-dysk.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.aquino.2014.s113">Aquino CC, Lang AE. Tardive dyskinesia syndromes: current concepts. <span><span class="ref-journal">Parkinsonism Relat Disord. </span>2014;<span class="ref-vol">20</span> Suppl 1:S113–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24262160" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24262160</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.barrett.2017.193">Barrett MJ, Williams ES, Chambers C, Dhamija R. Autosomal recessive inheritance of ADCY5-related generalized dystonia and myoclonus. <span><span class="ref-journal">Neurol Genet. </span>2017;<span class="ref-vol">3</span>:193.</span> [<a href="/pmc/articles/PMC5612768/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5612768</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28971144" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28971144</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.bohlega.2019.145">Bohlega SA, Abou-Al-Shaar HA, AlDakheel A, Alajlan H, Bohlega BS, Meyer BF, Monies D, Cupler EJ, Al-Saif AM. Autosomal recessive ADCY5-Related dystonia and myoclonus: expanding the genetic spectrum of ADCY5-related movement disorders. <span><span class="ref-journal">Parkinsonism Relat Disord. </span>2019;<span class="ref-vol">64</span>:145–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30975617" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30975617</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.carapito.2015.423">Carapito R, Paul N, Untrau M, Le Gentil M, Ott L, Alsaleh G, Jochem P, Radosavljevic M, Le Caignec C, David A, Darnier P, Isidor B, Bahram S. A de novo ADCY5 mutation causes early-onset autosomal dominant chorea and dystonia. <span><span class="ref-journal">Movement Dis. </span>2015;<span class="ref-vol">30</span>:423–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25545163" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25545163</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.carecchio.2017.37">Carecchio M, Mencacci NE, Iodice A, Pons R, Panteghini C, Zorzi G, Zibordi F, Bonakis A, Dinopoulos A, Jankovic J, Stefanis L, Bhatia KP, Monti V. R'Bibo L, Veneziano L, Garavaglia B, Fusco C, Wood N, Stamelou M, Nardocci N. ADCY5-related movement disorders: Frequency, disease course and phenotypic variability in a cohort of paediatric patients. <span><span class="ref-journal">Parkinsonism Relat Disord. </span>2017;<span class="ref-vol">41</span>:37–43.</span> [<a href="/pmc/articles/PMC5549507/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5549507</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28511835" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28511835</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.chang.2016.1033">Chang FC, Westenberger A, Dale RC, Smith M, Pall HS, Perez-Dueñas B, Grattan-Smith P, Ouvrier RA, Mahant N, Hanna BC, Hunter M, Lawson JA, Max C, Sachdev R, Meyer E, Crimmins D, Pryor D, Morris JG, Münchau A, Grozeva D, Carss KJ, Raymond L, Kurian MA, Klein C, Fung VS. Phenotypic insights into ADCY5-associated disease. <span><span class="ref-journal">Mov Disord. </span>2016;<span class="ref-vol">31</span>:1033–40.</span> [<a href="/pmc/articles/PMC4950003/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4950003</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27061943" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27061943</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.chen.2016">Chen DH, Friedman J, Méneret A, Bonkowski E, Hisama F, Davis M, Swanson P, Bernes S, Vidailhet M, Roze E, Bird T, Raskind W. Likely underrecognized mosaicism in genetic disease: high frequency of mosaic mutations in ADCY5-related dyskinesia. Neurology. 2016;86(16 Suppl):P5.398.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.chen.2019.70">Chen DH, Latimer CS, Spencer M, Karna P, Gonzalez-Cuyar LF, Davis MY, Keene CD, Bird TD, Raskind WH. Hyperphosphorylated tau, increased adenylate cyclase 5 (ADCY5) immunoreactivity, but no neuronal loss in ADCY5-dyskinesia. <span><span class="ref-journal">Mov Disord Clin Pract. </span>2019;<span class="ref-vol">7</span>:70–7.</span> [<a href="/pmc/articles/PMC6962666/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6962666</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31970214" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31970214</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.chen.2015.2026">Chen DH, Méneret A, Friedman JR, Korvatska O, Gad A, Bonkowski ES, Stessman HA, Doummar D, Mignot C, Anheim M, Bernes S, Davis MY, Damon-Perrière N, Degos B, Grabli D, Gras D, Hisama FM, Mackenzie KM, Swanson PD, Tranchant C, Vidailhet M, Trouillard O, Amendola LM, Dorschner MO, Weiss M, Eichler EE, Winesett S, Torkamani A, Roze E, Bird TD, Raskind WH. ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations. <span><span class="ref-journal">Neurology. </span>2015;<span class="ref-vol">85</span>:2026–35.</span> [<a href="/pmc/articles/PMC4676753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4676753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26537056" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26537056</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.chen.2011.1252">Chen WJ, Lin Y, Xiong ZQ, Wei W, Ni W, Tan GH, Guo SL, He J, Chen YF, Zhang QJ, Li HF, Lin Y, Murong SX, Xu J, Wang N, Wu ZY. Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia. <span><span class="ref-journal">Nat Genet. </span>2011;<span class="ref-vol">43</span>:1252–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22101681" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22101681</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.chen.2014.542">Chen YZ, Friedman JR, Chen DH, Chan GC, Bloss CS, Hisama FM, Topol SE, Carson AR, Pham PH, Bonkowski ES, Scott ER, Lee JK, Zhang G, Oliveira G, Xu J, Scott-Van Zeeland AA, Chen Q, Levy S, Topol EJ, Storm D, Swanson PD, Bird TD, Schork NJ, Raskind WH, Torkamani A. Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia. <span><span class="ref-journal">Ann Neurol. </span>2014;<span class="ref-vol">75</span>:542–9.</span> [<a href="/pmc/articles/PMC4457323/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4457323</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24700542" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24700542</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.chen.2012.630">Chen YZ, Matsushita MM, Robertson P, Rieder M, Girirajan S, Antonacci F, Lipe H, Eichler EE, Nickerson DA, Bird TD, Raskind WH. Autosomal dominant familial dyskinesia and facial myokymia: single exome sequencing identifies a mutation in adenylyl cyclase 5. <span><span class="ref-journal">Arch Neurol. </span>2012;<span class="ref-vol">69</span>:630–5.</span> [<a href="/pmc/articles/PMC3508680/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3508680</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22782511" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22782511</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.dean.2019.510">Dean M, Messiaen L, Cooper GM, Amaral MD, Rashid S, Korf BR, Standaert DG. Child Neurology: Spastic paraparesis and dystonia with a novel ADCY5 mutation. <span><span class="ref-journal">Neurology. </span>2019;<span class="ref-vol">93</span>:510–4.</span> [<a href="/pmc/articles/PMC6746208/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6746208</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31501304" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31501304</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.dy.2016.1027">Dy ME, Chang FC, Jesus SD, Anselm I, Mahant N, Zeilman P, Rodan LH, Foote KD, Tan WH, Eskandar E, Sharma N, Okun MS, Fung VS, Waugh JL. Treatment of ADCY5-associated dystonia, chorea, and hyperkinetic disorders with deep brain stimulation: a multicenter case series. <span><span class="ref-journal">J Child Neurol. </span>2016;<span class="ref-vol">31</span>:1027–35.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27052971" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27052971</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.fernandez.2001.486">Fernandez M, Raskind W, Wolff J, Matsushita M, Yuen E, Graf W, Lipe H, Bird T. Familial dyskinesia and facial myokymia (FDFM): a novel movement disorder. <span><span class="ref-journal">Ann Neurol. </span>2001;<span class="ref-vol">49</span>:486–92.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11310626" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11310626</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.friedman.2016.147">Friedman JR, Meneret A, Chen DH, Trouillard O, Vidailhet M, Raskind WH, Roze E. ADCY5 mutation carriers display pleiotropic paroxysmal day and nighttime dyskinesias. <span><span class="ref-journal">Mov Disord. </span>2016;<span class="ref-vol">31</span>:147–8.</span> [<a href="/pmc/articles/PMC4724296/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4724296</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26686870" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26686870</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.halls.2017.171">Halls ML, Cooper DMF. Adenylyl cyclase signalling complexes - Pharmacological challenges and opportunities. <span><span class="ref-journal">Pharmacol Ther. </span>2017;<span class="ref-vol">172</span>:171–80.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28132906" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28132906</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.ho.2010.495">Ho D, Yan L, Iwatsubo K, Vatner DE, Vatner SF. Modulation of beta-adrenergic receptor signaling in heart failure and longevity: targeting adenylyl cyclase type 5. <span><span class="ref-journal">Heart Fail Rev. </span>2010;<span class="ref-vol">15</span>:495–512.</span> [<a href="/pmc/articles/PMC3655553/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3655553</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20658186" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20658186</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.j_nsson.2017.519">Jónsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F, Hjartarson E, Hardarson MT, Hjorleifsson KE, Eggertsson HP, Gudjonsson SA, Ward LD, Arnadottir GA, Helgason EA, Helgason H, Gylfason A, Jonasdottir A, Jonasdottir A, Rafnar T, Frigge M, Stacey SN, Th Magnusson O, Thorsteinsdottir U, Masson G, Kong A, Halldorsson BV, Helgason A, Gudbjartsson DF, Stefansson K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. <span><span class="ref-journal">Nature. </span>2017;<span class="ref-vol">549</span>:519–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28959963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28959963</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.marras.2012.1016">Marras C, Lohmann K, Lang A, Klein C. Fixing the broken system of genetic locus symbols: Parkinson disease and dystonia as examples. <span><span class="ref-journal">Neurology. </span>2012;<span class="ref-vol">78</span>:1016–24.</span> [<a href="/pmc/articles/PMC3310311/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3310311</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22454269" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22454269</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.meijer.2017.438">Meijer IA, Miravite J, Kopell BH, Lubarr N. Deep brain stimulation in an additional patient with ADCY5-related movement disorder. <span><span class="ref-journal">J Child Neurol. </span>2017;<span class="ref-vol">32</span>:438–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27920267" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27920267</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.mencacci.2015.80">Mencacci NE, Erro R, Wiethoff S, Hersheson J, Ryten M, Balint B, Ganos C, Stamelou M, Quinn N, Houlden H, Wood NW, Bhatia KP. ADCY5 mutations are another cause of benign hereditary chorea. <span><span class="ref-journal">Neurology. </span>2015;<span class="ref-vol">85</span>:80–8.</span> [<a href="/pmc/articles/PMC4501937/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4501937</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26085604" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26085604</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.mencacci.2016.763">Mencacci NE, Kamsteeg EJ, Nakashima K. R'Bibo L, Lynch DS, Balint B, Willemsen MA, Adams ME, Wiethoff S, Suzuki K, Davies CH, Ng J, Meyer E, Veneziano L, Giunti P, Hughes D, Raymond FL, Carecchio M, Zorzi G, Nardocci N, Barzaghi C, Garavaglia B, Salpietro V, Hardy J, Pittman AM, Houlden H, Kurian MA, Kimura H, Vissers LE, Wood NW, Bhatia KP. De novo mutations in PDE10A cause childhood-onset chorea with bilateral striatal lesions. <span><span class="ref-journal">Am J Hum Genet. </span>2016;<span class="ref-vol">98</span>:763–71.</span> [<a href="/pmc/articles/PMC4833291/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4833291</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27058447" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27058447</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.raskind.2017.305">Raskind WH, Friedman JR, Roze E, Meneret A, Chen DH, Bird TD. ADCY5-related dysinesia: comments on characteristic manifestations and variant-associated severity. <span><span class="ref-journal">Mov Disord. </span>2017;<span class="ref-vol">32</span>:305–6.</span> [<a href="/pmc/articles/PMC5318268/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5318268</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27933653" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27933653</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.richards.2015.405">Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL., ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. <span><span class="ref-journal">Genet Med. </span>2015;<span class="ref-vol">17</span>:405–24.</span> [<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.stenson.2020.1197">Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, Hayden M, Heywood S, Millar DS, Phillips AD, Cooper DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting. <span><span class="ref-journal">Hum Genet. </span>2020;<span class="ref-vol">139</span>:1197–207.</span> [<a href="/pmc/articles/PMC7497289/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7497289</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32596782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32596782</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.vijiaratnam.2019.512">Vijiaratnam N, Bhatia KP, Lang AE, Raskind WH, Espay AJ. ADCY5-related dyskinesia: improving clinical detection of an evolving disorder. <span><span class="ref-journal">Mov Disord Clin Pract. </span>2019;<span class="ref-vol">6</span>:512–20.</span> [<a href="/pmc/articles/PMC6749814/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6749814</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31538084" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31538084</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.waalkens.2018.e214">Waalkens AJE, Vansenne F, van der Hout AH, Zutt R, Mourmans J, Tolosa E, de Koning TJ, Tijssen MAJ. Expanding the ADCY5 phenotype toward spastic paraparesis: a mutation in the M2 domain. <span><span class="ref-journal">Neurol Genet. </span>2018;<span class="ref-vol">4</span>:e214. </span> [<a href="/pmc/articles/PMC5820596/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5820596</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29473048" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29473048</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.westenberger.2017.306">Westenberger A, Max C, Brüggemann N, Domingo A, Grütz K, Pawlack H, Weissbach A, Kühn AA, Spiegler J, Lang AE, Sperner J, Fung VSC, Schallner J, Gillessen-Kaesbach G, Münchau A, Klein C. Alternating hemiplegia of childhood as a new presentation of adenylate cyclase 5-mutation-associated disease: a report of two cases. <span><span class="ref-journal">J Pediatr. </span>2017;<span class="ref-vol">181</span>:306–8.e1.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27931826" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27931826</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="adcy5-dysk.REF.zech.2017.549">Zech M, Boesch S, Jochim A, Weber S, Meindl T, Schormair B, Wieland T, Lunetta C, Sansone V, Messner M, Mueller J, Ceballos-Baumann A, Strom TM, Colombo R, Poewe W, Haslinger B, Winkelmann J. Clinical exome sequencing in early-onset generalized dystonia and large-scale resequencing follow-up. <span><span class="ref-journal">Mov Disord. </span>2017;<span class="ref-vol">32</span>:549–59.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27666935" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27666935</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK263441_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Fuki M Hisama</span>, MD<div class="affiliation small">Division of Medical Genetics<br />Department of Medicine<br />University of Washington<br />Seattle, Washington<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.wu@2hmf" class="oemail">ude.wu@2hmf</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Jennifer Friedman</span>, MD<div class="affiliation small">Departments of Neuroscience and Pediatrics<br />University of California San Diego;<br />Rady Children’s Hospital and Rady Children’s Institute for Genomic Medicine<br />San Diego, California<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.dshcr@namdeirfrj" class="oemail">gro.dshcr@namdeirfrj</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Wendy H Raskind</span>, MD, PhD<div class="affiliation small">Division of Medical Genetics<br />Department of Medicine<br />University of Washington<br />Seattle, Washington<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.wu@nurydnew" class="oemail">ude.wu@nurydnew</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Thomas D Bird</span>, MD<div class="affiliation small">Seattle VA Medical Center;<br />Departments of Neurology and Medicine<br />University of Washington<br />Seattle, Washington<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.wu@zornmot" class="oemail">ude.wu@zornmot</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">December 18, 2014</span>; Last Update: <span itemprop="dateModified">July 30, 2020</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Hisama FM, Friedman J, Raskind WH, et al. ADCY5 Dyskinesia. 2014 Dec 18 [Updated 2020 Jul 30]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/adamtsl4-eyes/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/adnp-dis/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobadcy5dyskTmoleculargenetictestingu"><div id="adcy5-dysk.T.molecular_genetic_testing_u" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>ADCY5</i> Dyskinesia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK263441/table/adcy5-dysk.T.molecular_genetic_testing_u/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adcy5-dysk.T.molecular_genetic_testing_u_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_adcy5-dysk.T.molecular_genetic_testing_u_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_adcy5-dysk.T.molecular_genetic_testing_u_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_adcy5-dysk.T.molecular_genetic_testing_u_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_adcy5-dysk.T.molecular_genetic_testing_u_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ADCY5</i>
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</td><td headers="hd_h_adcy5-dysk.T.molecular_genetic_testing_u_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_adcy5-dysk.T.molecular_genetic_testing_u_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100% <sup>4, 5</sup></td></tr><tr><td headers="hd_h_adcy5-dysk.T.molecular_genetic_testing_u_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>6</sup></td><td headers="hd_h_adcy5-dysk.T.molecular_genetic_testing_u_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported <sup>7</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="adcy5-dysk.TF.1.1"><p class="no_margin">See <a href="/books/NBK263441/?report=reader#adcy5-dysk.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="adcy5-dysk.TF.1.2"><p class="no_margin">See <a href="#adcy5-dysk.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="adcy5-dysk.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="adcy5-dysk.TF.1.4"><p class="no_margin"><a class="bibr" href="#adcy5-dysk.REF.chen.2012.630" rid="adcy5-dysk.REF.chen.2012.630">Chen et al [2012]</a>, <a class="bibr" href="#adcy5-dysk.REF.chen.2014.542" rid="adcy5-dysk.REF.chen.2014.542">Chen et al [2014]</a>, <a class="bibr" href="#adcy5-dysk.REF.chen.2015.2026" rid="adcy5-dysk.REF.chen.2015.2026">Chen et al [2015]</a>, <a class="bibr" href="#adcy5-dysk.REF.zech.2017.549" rid="adcy5-dysk.REF.zech.2017.549">Zech et al [2017]</a>, and data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bibr" href="#adcy5-dysk.REF.stenson.2020.1197" rid="adcy5-dysk.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="adcy5-dysk.TF.1.5"><p class="no_margin">In a simplex case (i.e., a single occurrence in a family), germline mosaicism for the pathogenic variant may complicate interpretation of sequencing results.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="adcy5-dysk.TF.1.6"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="adcy5-dysk.TF.1.7"><p class="no_margin">Because <i>ADCY5</i> dyskinesia occurs through a gain-of-function mechanism and large intragenic deletion or duplication has not been reported, testing for intragenic deletions or duplication is unlikely to identify a disease causing variant.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobadcy5dyskTadcy5dyskinesiafrequency"><div id="adcy5-dysk.T.adcy5_dyskinesia_frequency" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>ADCY5</i> Dyskinesia: Frequency of Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK263441/table/adcy5-dysk.T.adcy5_dyskinesia_frequency/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adcy5-dysk.T.adcy5_dyskinesia_frequency_lrgtbl__"><table><thead><tr><th id="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2" colspan="3" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Frequency</th><th id="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_3" style="text-align:left;vertical-align:middle;">Comment</th></tr><tr><th headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2" id="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Nearly all</th><th headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2" id="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common</th><th headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2" id="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infrequent</th></tr></thead><tbody><tr><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dyskinesia</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Axial hypotonia</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In children presenting in infancy</td></tr><tr><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Spasticity</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Intellectual disability</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Epilepsy</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Psychiatric disease</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardiomyopathy</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_2 hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_adcy5-dysk.T.adcy5_dyskinesia_frequency_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobadcy5dyskTgenesofinterestinthedi"><div id="adcy5-dysk.T.genes_of_interest_in_the_di" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Genes of Interest in the Differential Diagnosis of <i>ADCY5</i> Dyskinesia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK263441/table/adcy5-dysk.T.genes_of_interest_in_the_di/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adcy5-dysk.T.genes_of_interest_in_the_di_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" style="text-align:left;vertical-align:middle;">DiffDx Disorder</th><th id="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Characteristics of DiffDx Disorder</th></tr><tr><th headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4" id="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/<i>ADCY5</i> dyskinesia</th><th headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4" id="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from <i>ADCY5</i> dyskinesia</th></tr></thead><tbody><tr><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ANO3</i>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DYT-<i>ANO3</i> (See <a href="/books/n/gene/dystonia-ov/?report=reader">Hereditary Dystonia Overview</a>.)</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Focal dystonia & tremor</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Affects neck, laryngeal muscles, and arms</td></tr><tr><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ATP1A3</i>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Alternating hemiplegia of childhood (See <a href="/books/n/gene/rapid-odp/?report=reader"><i>ATP1A3</i> Neurologic Disorders</a>.)</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Alternating hemiplegia</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Episodic hemiplegia assoc w/mvmt disorder</td></tr><tr><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CHRNA2</i>
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<br />
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<i>CHRNA4</i>
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<br />
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<i>CHRNB2</i>
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<br />
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<i>CRH</i>
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<br />
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<i>DEPDC5</i>
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<br />
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<i>KCNT1</i>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/adnfle/?report=reader">AD nocturnal frontal lobe epilepsy</a>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sleep-related motor & behavioral disorders</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">On video-EEG: focal interictal epileptiform discharges arising from the frontal lobe; seizures recorded</td></tr><tr><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GCH1</i>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/drd/?report=reader">GTP cyclohydrolase 1-deficient dopa-responsive dystonia</a>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dystonia</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dramatic response to treatment w/L-dopa</td></tr><tr><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HTT</i>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/huntington/?report=reader">Huntington disease</a>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Chorea</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Mean onset age: 35-44 yrs</div></li><li class="half_rhythm"><div>Choreiform mvmts become constant over time.</div></li></ul>
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</td></tr><tr><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>NKX2-1</i>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Benign hereditary chorea (See <a href="/books/n/gene/nkx2-1-dis/?report=reader"><i>NKX2-1</i> Disorders</a>.)</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Presents before age 5 yrs</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Manifestations often improve by late adolescence.</div></li><li class="half_rhythm"><div>Pulmonary dysfunction & endocrine abnormalities, most commonly hypothyroidism (Note: Non-neurologic manifestations are rare in <i>ADCY5</i> dyskinesia.)</div></li></ul>
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</td></tr><tr><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>PDE10A</i>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infantile-onset limb & orofacial dyskinesia (OMIM <a href="https://omim.org/entry/616921" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">616921</a>)</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood onset chorea</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Diurnal fluctuation</div></li><li class="half_rhythm"><div>Striatal lesions on brain MRI</div></li></ul>
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</td></tr><tr><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>PDE2A</i>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>PDE10A</i> childhood-onset chorea <sup>1</sup></td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Childhood onset chorea</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Striatal lesions on brain MRI</td></tr><tr><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>PNKD</i>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/pnknd/?report=reader">Familial paroxysmal nonkinesigenic dyskinesia</a>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Unilateral or bilateral involuntary mvmts</div></li><li class="half_rhythm"><div>Attacks are spontaneous or precipitated; involve dystonic posturing w/choreic & ballistic mvmts; may be accompanied by preceding aura; occur while awake; are not assoc w/seizures.</div></li></ul>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consumption of alcohol or caffeine may precipitate attacks</td></tr><tr><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>PRRT2</i>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Paroxysmal kinesigenic dyskinesia (PKD) (See <a href="/books/n/gene/prrt2-parox/?report=reader"><i>PRRT2</i> Paroxysmal Movement Disorders</a>.)</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Unilateral or bilateral involuntary mvmts precipitated by other sudden mvmts (e.g., standing up from sitting position; being startled; changes in velocity).</div></li><li class="half_rhythm"><div>Attacks incl combinations of dystonia, choreoathetosis, & ballism; are sometimes preceded by an aura; do not involve loss of consciousness.</div></li></ul>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PKD is more common in men & is precipitated by voluntary mvmt.</td></tr><tr><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SGCE</i>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/myo-dystonia/?report=reader"><i>SGCE</i> myoclonus-dystonia</a>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Myoclonus-dystonia</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Improves w/alcohol consumption; psychiatric manifestations are more common.</td></tr><tr><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SLC2A1</i>
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</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Paroxysmal choreoathetosis w/spasticity (See <a href="/books/n/gene/glut1/?report=reader">Glucose Transporter Type 1 Deficiency Syndrome</a>.)</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />(AR)</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Presents w/dystonic paroxysms affecting toes, legs, & arms; dysarthria; & changes in perioral sensation</td><td headers="hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_1_4 hd_h_adcy5-dysk.T.genes_of_interest_in_the_di_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No distinguishing clinical characteristics</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; DYT = dystonia; MOI = mode of inheritance</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="adcy5-dysk.TF.3.1"><p class="no_margin">
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<a class="bibr" href="#adcy5-dysk.REF.mencacci.2016.763" rid="adcy5-dysk.REF.mencacci.2016.763">Mencacci et al [2016]</a>
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</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobadcy5dyskTrecommendedevaluationsfol"><div id="adcy5-dysk.T.recommended_evaluations_fol" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with <i>ADCY5</i> Dyskinesia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK263441/table/adcy5-dysk.T.recommended_evaluations_fol/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adcy5-dysk.T.recommended_evaluations_fol_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_adcy5-dysk.T.recommended_evaluations_fol_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_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic</b>
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<br />
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<b>involvement</b>
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</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By a neurologist</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess:
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<ul><li class="half_rhythm"><div>Neurologic findings incl spasticity, dystonic posturing, sleep-related mvmts;</div></li><li class="half_rhythm"><div>Response or lack of response to medications.</div></li></ul>
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</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Oculomotor</b>
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<br />
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<b>involvement</b>
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</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complete ophthalmologic exam</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess best corrected visual acuity; nystagmus, saccades & smooth pursuit; vertical & horizontal gaze limitation; ptosis.</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Musculoskeletal</b>
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</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT/OT eval</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl assessment of:
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<ul><li class="half_rhythm"><div>Gross motor & fine motor skills</div></li><li class="half_rhythm"><div>Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills)</div></li><li class="half_rhythm"><div>Mobility, self-help skills, activities of daily living, & need for adaptive devices</div></li></ul>
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</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>DD / Cognitive</b>
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<br />
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<b>impairment</b>
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</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental behavioral pediatrician, neurologist, or geneticist</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Children: To incl motor, adaptive, cognitive, & speech/language eval; eval for early intervention / special education</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Clinical psychologist</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adults: Assess for deficits in spatial working & episodic memory</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Dysarthria</b>
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</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Speech & language assessment</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Related to abnormal tongue & facial mvmts</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Psychiatric</b>
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<br />
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<b>manifestations</b>
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</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Child psychiatrist</div></li><li class="half_rhythm"><div>Clinical psychologist</div></li></ul>
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</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Depression, psychosis w/delusions & auditory hallucinations, obsessive-compulsive symptoms, autistic-like behavior</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cardiac</b>
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<br />
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<b>involvement</b>
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</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">EKG, echocardiogram, cardiology eval</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dilated cardiomyopathy may be a manifestation.</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic counseling</b>
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</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of <i>ADCY5</i> dyskinesia in order to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family support/</b>
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<br />
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<b>resources</b>
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</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess:
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<ul><li class="half_rhythm"><div>Use of community or online <a href="#adcy5-dysk.Resources">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>Need for social work involvement for parental support;</div></li><li class="half_rhythm"><div>Need for home nursing referral.</div></li></ul>
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</td><td headers="hd_h_adcy5-dysk.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disease severity may qualify some persons for disability &/or social security benefits.</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">DD = developmental delay; MOI= mode of inheritance; OT = occupational therapy; PT = physical therapy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="adcy5-dysk.TF.4.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobadcy5dyskTtreatmentofmanifestations"><div id="adcy5-dysk.T.treatment_of_manifestations" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <i>ADCY5</i> Dyskinesia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK263441/table/adcy5-dysk.T.treatment_of_manifestations/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adcy5-dysk.T.treatment_of_manifestations_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/<br />Concern</th><th id="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_adcy5-dysk.T.treatment_of_manifestations_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_adcy5-dysk.T.treatment_of_manifestations_1_1_1_1 hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" rowspan="4" colspan="2" scope="row" style="text-align:left;vertical-align:middle;">
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<b>Chorea &</b>
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<br />
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<b>dyskinesia</b>
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</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Acetazolamide</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Up to 30 mg/kg/day</td></tr><tr><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Other potentially beneficial medications</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Trihexyphenidyl</div></li><li class="half_rhythm"><div>Tetrabenazine</div></li><li class="half_rhythm"><div>Clonazepam</div></li><li class="half_rhythm"><div>Propranolol</div></li><li class="half_rhythm"><div>Levocarnitine</div></li><li class="half_rhythm"><div>Levetirracetam</div></li><li class="half_rhythm"><div>Methylphenidate</div></li></ul>
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</td></tr><tr><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Medications that may worsen manifestations</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Any of the above</td></tr><tr><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deep brain stimulation</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Improves mvmt disorder in some persons refractory to medical treatment <sup>1</sup></td></tr><tr><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_1 hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" rowspan="2" colspan="2" scope="row" style="text-align:left;vertical-align:middle;">
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<b>Sleep-related</b>
|
|
<br />
|
|
<b>movements</b>
|
|
</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clonazepam</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Improves nocturnal dystonia & axial hypotonia in some</td></tr><tr><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Other potentially beneficial medications</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Melatonin</td></tr><tr><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_1 hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Dysarthria</b>
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</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Speech/language eval</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider alternative communication methods as needed (e.g., writing pads & digital devices).</td></tr><tr><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_1 hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Oculomotor</b>
|
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<br />
|
|
<b>involvement</b>
|
|
</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating ophthalmologist</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_1 hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Musculoskeletal</b>
|
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</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT/OT</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To help maintain mobility & function</div></li><li class="half_rhythm"><div>Walking aids incl canes or walkers when appropriate</div></li><li class="half_rhythm"><div>Durable medical equipment & positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers)</div></li><li class="half_rhythm"><div>Home adaptations for safety & function</div></li><li class="half_rhythm"><div>Consider disability parking placard for care-givers.</div></li></ul>
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</td></tr><tr><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_1 hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Developmental</b>
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<br />
|
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<b>delay</b>
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</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#adcy5-dysk.Developmental_Delay__Intellec">Developmental Delay / Intellectual Disability Management Issues</a>.</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_1 hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cognitive</b>
|
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<br />
|
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<b>impairment</b>
|
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</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Developmental eval</div></li><li class="half_rhythm"><div>Individualized education plan</div></li></ul>
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</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To identify degree of disability & provide resources for learning</td></tr><tr><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_1 hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Psychiatric</b>
|
|
<br />
|
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<b>manifestations</b>
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</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><ul><li class="half_rhythm"><div>Cognitive behavioral therapy</div></li><li class="half_rhythm"><div>Medication</div></li><li class="half_rhythm"><div>Mental health professionals</div></li></ul>
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</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_1 hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family support/</b>
|
|
<br />
|
|
<b>resources</b>
|
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</td><td headers="hd_h_adcy5-dysk.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ensure appropriate social work involvement to:
|
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<ul><li class="half_rhythm"><div>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_adcy5-dysk.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="adcy5-dysk.TF.5.1"><p class="no_margin">Reported in fewer than 5 persons with overall beneficial effects [<a class="bibr" href="#adcy5-dysk.REF.dy.2016.1027" rid="adcy5-dysk.REF.dy.2016.1027">Dy et al 2016</a>, <a class="bibr" href="#adcy5-dysk.REF.meijer.2017.438" rid="adcy5-dysk.REF.meijer.2017.438">Meijer et al 2017</a>]</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobadcy5dyskTrecommendedsurveillancefo"><div id="adcy5-dysk.T.recommended_surveillance_fo" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with <i>ADCY5</i> Dyskinesia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK263441/table/adcy5-dysk.T.recommended_surveillance_fo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adcy5-dysk.T.recommended_surveillance_fo_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_adcy5-dysk.T.recommended_surveillance_fo_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_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Neurologic involvement</b>
|
|
</td><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for new manifestations incl changes in tone, scoliosis, & mvmt disorders.</td><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Dysarthria</b>
|
|
</td><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Speech & language eval incl need for alternative communication methods</td><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Oculomotor involvement</b>
|
|
</td><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating ophthalmologist</td><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As clinically indicated</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Musculoskeletal /</b>
|
|
<br />
|
|
<b>Activities of daily living</b>
|
|
</td><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PT/OT eval</td><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_3" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Developmental delay</b>
|
|
</td><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs.</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Cognitive impairment</b>
|
|
</td><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neuropsychological testing; developmental eval</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Psychiatric manifestations</b>
|
|
</td><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for changes in mood, attention, psychosis, or obsessive-compulsive disorder.</td></tr><tr><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Cardiac involvement</b>
|
|
</td><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">EKG, echocardiogram, cardiac MRI</td><td headers="hd_h_adcy5-dysk.T.recommended_surveillance_fo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As clinically indicated</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">OT = occupational therapy; PT = physical therapy</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobadcy5dyskmolgenTA"><div id="adcy5-dysk.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>ADCY5 Dyskinesia: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK263441/table/adcy5-dysk.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adcy5-dysk.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_adcy5-dysk.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_adcy5-dysk.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_adcy5-dysk.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_adcy5-dysk.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_adcy5-dysk.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_adcy5-dysk.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/111" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>ADCY5</i>
|
|
</a>
|
|
</td><td headers="hd_b_adcy5-dysk.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=111" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">3q21<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_b_adcy5-dysk.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/O95622" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Adenylate cyclase type 5</a>
|
|
</td><td headers="hd_b_adcy5-dysk.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ADCY5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ADCY5</a>
|
|
</td><td headers="hd_b_adcy5-dysk.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ADCY5[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ADCY5</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="adcy5-dysk.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
|
|
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
|
chromosome locus 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/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobadcy5dyskmolgenTB"><div id="adcy5-dysk.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for ADCY5 Dyskinesia (<a href="/omim/600293,606703" 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/NBK263441/table/adcy5-dysk.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adcy5-dysk.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/600293" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">600293</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ADENYLATE CYCLASE 5; ADCY5</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/606703" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">606703</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL DOMINANT; DSKOD</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobadcy5dyskTnotableadcy5pathogenicva"><div id="adcy5-dysk.T.notable_adcy5_pathogenic_va" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Notable <i>ADCY5</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK263441/table/adcy5-dysk.T.notable_adcy5_pathogenic_va/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adcy5-dysk.T.notable_adcy5_pathogenic_va_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide<br />Change</th><th id="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted<br />Protein Change</th><th id="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_183357.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_183357<wbr style="display:inline-block"></wbr>​.3</a>
|
|
<br />
|
|
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_899200.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_899200<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1252C>T</td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg418Trp <sup>1</sup></td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_4" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Recurrent <i>de novo</i> pathogenic variants affecting the same residue [<a class="bibr" href="#adcy5-dysk.REF.chen.2014.542" rid="adcy5-dysk.REF.chen.2014.542">Chen et al 2014</a>, <a class="bibr" href="#adcy5-dysk.REF.chen.2015.2026" rid="adcy5-dysk.REF.chen.2015.2026">Chen et al 2015</a>, <a class="bibr" href="#adcy5-dysk.REF.chang.2016.1033" rid="adcy5-dysk.REF.chang.2016.1033">Chang et al 2016</a>]</td></tr><tr><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1252C>G</td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg418Gly</td></tr><tr><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1253G>A</td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg418Gln</td></tr><tr><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1762G>A</td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Asp588Asn</td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assoc w/autosomal recessive inheritance [<a class="bibr" href="#adcy5-dysk.REF.barrett.2017.193" rid="adcy5-dysk.REF.barrett.2017.193">Barrett et al 2017</a>, <a class="bibr" href="#adcy5-dysk.REF.bohlega.2019.145" rid="adcy5-dysk.REF.bohlega.2019.145">Bohlega et al 2019</a>]</td></tr><tr><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_183357.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_183357<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.2088+1G>A</td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Apparent loss-of-function variant w/unclear disease mechanism [<a class="bibr" href="#adcy5-dysk.REF.carapito.2015.423" rid="adcy5-dysk.REF.carapito.2015.423">Carapito et al 2015</a>]</td></tr><tr><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_183357.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_183357<wbr style="display:inline-block"></wbr>​.3</a>
|
|
<br />
|
|
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_899200.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_899200<wbr style="display:inline-block"></wbr>​.1</a>
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</td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.2176G>A</td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ala726Thr</td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assoc w/milder phenotype [<a class="bibr" href="#adcy5-dysk.REF.vijiaratnam.2019.512" rid="adcy5-dysk.REF.vijiaratnam.2019.512">Vijiaratnam et al 2019</a>]</td></tr><tr><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.3086T>A</td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Met1029Lys <sup>2</sup></td><td headers="hd_h_adcy5-dysk.T.notable_adcy5_pathogenic_va_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assoc w/somatic mosaicism [<a class="bibr" href="#adcy5-dysk.REF.chen.2015.2026" rid="adcy5-dysk.REF.chen.2015.2026">Chen et al 2015</a>]</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">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></dl><dl class="bkr_refwrap"><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/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="adcy5-dysk.TF.7.1"><p class="no_margin">See <a href="#adcy5-dysk.GenotypePhenotype_Correlation">Genotype-Phenotype Correlations</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="adcy5-dysk.TF.7.2"><p class="no_margin">See Clinical Description, <a href="#adcy5-dysk.Neurologic_Manifestations">Neurologic Manifestations</a>.</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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