Myoclonus-Dystonia: SGCE Gene Deletion/Duplication

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Condition Description

Myoclonus-dystonia (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). Onset of myoclonus is usually in the first or second decade of life. The myoclonic jerks typical of M-D are brief, lightning-like movements that most often affect the neck, trunk, and upper limbs with less common involvement of the legs. Dystonia is observed in more than half of affected individuals, but is only rarely seen without myoclonus. Affected individuals can have focal or segmental dystonia, presenting as cervical dystonia and/or writer's cramp. Most affected adults report a dramatic reduction in myoclonus in response to alcohol ingestion. The most prominent non-motor features have been psychiatric problems including depression, anxiety, obsessive-compulsive disorder (OCD), personality disorders, addiction, and panic attacks.

The diagnosis of myoclonus-dystonia is based on clinical findings, family history, absence of other neurologic deficits, and normal neuroimaging studies. In general, all laboratory tests are normal in individuals with M-D. Abnormal liver function tests may be the result of chronic alcohol use.

Myoclonus-dystonia is inherited in an autosomal dominant manner. Mutations in the SGCE gene (7q21) are identified in approximately 30-50% of individuals with familial M-D and 10-15% of simplex cases. Simplex and familial cases without identifiable SGCE mutations have been reported, suggesting locus heterogeneity. Reduced penetrance on maternal transmission of the disease allele has been observed, suggesting maternal genomic imprinting of the SGCE gene. Almost all children who inherit the mutation from their fathers develop symptoms. About 5% of children who inherit the mutation from their mothers develop symptoms.

For patients with suspected myoclonus-dystonia, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.

References:

Genes (1)

Indications

This test is indicated for:

  • Confirmation of a clinical diagnosis of myoclonus-dystonia in an individual in whom sequence analysis was negative.

Methodology

DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.

Please note that a "backbone" of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off-target copy number variants causative of disease may be identified that may or may not be related to the patient's phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.

Detection

Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Submit only 1 of the following specimen types

Preferred specimen type: Whole Blood

Type: Whole Blood

Specimen Requirements:

In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva

Specimen Requirements:

OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of Emory Genetics Laboratory, please submit a copy of the sequencing report with the test requisition.
     



  • Sequence analysis of the SGCE gene is available and is required before deletion/duplication analysis.
  • Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
  • Prenatal testing is available to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.

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