SGCE Myoclonus-Dystonia

In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].


Clinical characteristics: SGCE myoclonus-dystonia (SGCE-M-D) is a movement disorder characterized by a combination of rapid, brief muscle contractions (myoclonus) and/or sustained twisting and repetitive movements that result in abnormal postures (dystonia). The myoclonic jerks typical of SGCE-M-D most often affect the neck, trunk, and upper limbs with less common involvement of the legs. Approximately 50% of affected individuals have additional focal or segmental dystonia, presenting as cervical dystonia and/or writer's cramp. Non-motor features may include alcohol abuse, obsessive-compulsive disorder (OCD), and anxiety disorders. Symptom onset is usually in the first decade of life and almost always by age 20 years, but ranges from age six months to 80 years. Most affected adults report a dramatic reduction in myoclonus in response to alcohol ingestion. SGCE-M-D is compatible with an active life of normal span.

Diagnosis/testing: The diagnosis of SGCE-M-D is established in a proband with characteristic clinical features by identification of a heterozygous pathogenic variant in SGCE.

Management: Treatment of manifestations: Class 1 evidence supports the improvement of myoclonus and dystonia with zonisamide. Benzodiazepines (particularly clonazepam) and anti-seizure drugs used to treat myoclonus (especially valproate and levitiracetam) also improve myoclonus in individuals with myoclonus-dystonia. The response to other anti-seizure drugs (e.g., topiramate) is more variable. Anticholinergic medication may improve dystonia. Botulinum toxin injection may be especially helpful for cervical dystonia. Improvement with L-5-hydroxytryptophan, L-dopa, and the salt of sodium oxybate has been reported. Deep brain stimulation has improved both myoclonus and dystonia, with most targeting the globus pallidus interna (GPi); however, success with ventral intermediate nucleus of the thalamus (VIM) target has also been reported.

Other: Symptoms of SGCE-M-D often improve short term with ingestion of alcohol, but the risk of addiction recommends against its long-term use.

Genetic counseling: SGCE-M-D is inherited in an autosomal dominant manner with penetrance determined by the parental origin of the altered SGCE allele: an SGCE pathogenic variant on the paternally derived (expressed) SGCE allele generally results in disease; a pathogenic variant on the maternally derived (silenced) SGCE allele typically does not result in disease. Most individuals with SGCE-M-D inherited the disorder from a heterozygous parent who may or may not have clinical signs of M-D (as phenotypic expression in the parent would depend on the sex of the transmitting grandparent). Each child of an individual with SGCE-M-D has a 50% chance of inheriting the pathogenic variant. Almost all children who inherit an SGCE pathogenic variant from their father develop symptoms, whereas only ~5% of children who inherit an SGCE pathogenic variant from their mother develop symptoms. Once the SGCE pathogenic variant has been identified in an affected family member, prenatal testing and preimplantation genetic diagnosis are possible.

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