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@INBOOK{Peikert:281114,
author = {Peikert, Kevin and Dobson-Stone, Carol and Rampoldi, Luca
and Miltenberger-Miltenyi, Gabriel and Neiman, Aaron and De
Camilli, Pietro and Hermann, Andreas and Walker, Ruth H and
Danek, Adrian},
title = {{VPS}13{A} {D}isease},
publisher = {University of Washington, Seattle},
reportid = {DZNE-2025-01075},
pages = {Online},
year = {2023},
comment = {GeneReviews},
booktitle = {GeneReviews},
abstract = {Excerpt:Clinical characteristics: VPS13A disease, caused by
VPS13A loss-of-function pathogenic variants, is
characterized by a spectrum of movement disorders (chorea,
dystonia, tics, sometimes parkinsonism); predominant
orofacial choreic and dystonic movements and tics (with
involuntary tongue protrusion on attempted swallowing,
habitual tongue and lip biting resulting in self-mutilation,
involuntary vocalizations); dysarthria and dysphagia;
psychiatric, cognitive, and behavioral changes ("frontal
lobe type"); seizures; and progressive neuromuscular
involvement. Huntingtonism (triad of progressive movement
disorder and cognitive and behavioral alterations) is a
typical presentation. Phenotypic variability is considerable
even within the same family, including for monozygotic
twins. Mean age of onset is about 30 years. VPS13A disease
runs a chronic progressive course and may lead to major
disability within a few years. Some affected individuals are
bedridden or wheelchair dependent by the third decade. Age
at death ranges from 28 to 61 years; several instances of
sudden unexplained death or death during epileptic seizures
have been reported.Diagnosis/testing: The diagnosis of
VPS13A disease is established in a proband with suggestive
findings and biallelic pathogenic variants in VPS13A
identified by molecular genetic testing.Management:
Treatment of manifestations: There is no cure for VPS13A
disease. Supportive treatment to improve quality of life,
maximize function, and reduce complications is recommended.
This ideally involves multidisciplinary care by specialists
in relevant fields of neurology, psychiatry, physiatry,
physical therapy (PT), occupational therapy (OT),
speech-language therapy, feeding, neuropsychology, and
medical genetics. Pharmacotherapy for movement disorders may
include dopamine antagonists/depleters such as atypical
neuroleptics or tetrabenazine (or its derivatives) for limb
and trunk dystonia and orofaciolingual dystonia (which may
also benefit from botulinum toxin). Issues with mobility,
activities of daily living, and need for assistive devices
can be addressed by physiatry, PT, and OT. In persons with
dysphagia, feeding assistance can include speech therapy and
gastrostomy tube placement as needed to reduce weight loss
and/or risk of aspiration. For dysarthria or mutism, therapy
can include the use of technical means for augmentative and
alternative communication, such as speech-generating
devices. Seizure management can include use of phenytoin,
clobazam, valproate, and levetiracetam. For
psychiatric/behavioral issues, antidepressant or
antipsychotic medications are used per conventional
approaches.Surveillance: Regular monitoring of existing
manifestations, the individual's response to pharmacotherapy
and other supportive care, and the emergence of new
manifestations is recommended per the multidisciplinary
treating specialists.Agents/circumstances to avoid:
Seizure-provoking circumstances (e.g., sleep deprivation,
alcohol intake) and anticonvulsants that may worsen
involuntary movements (e.g., carbamazepine,
lamotrigine).Genetic counseling: VPS13A disease is inherited
in an autosomal recessive manner. If both parents are known
to be heterozygous for a VPS13A 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. Once the VPS13A pathogenic variants have been
identified in an affected family member, carrier testing for
at-risk relatives, prenatal testing for a pregnancy at
increased risk, and preimplantation genetic testing are
possible.},
cin = {AG Hermann},
cid = {I:(DE-2719)1511100},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)7},
pubmed = {pmid:20301561},
url = {https://pub.dzne.de/record/281114},
}