Penetrance

Reduced penetrance on maternal transmission of the disease allele has been observed, suggesting that maternal genomic imprinting of SGCE suppresses expression of the maternally inherited SGCE allele .

• Consistent with this hypothesis, two studies demonstrated both paternal transmission of an SGCE pathogenic variant in affected individuals and DNA methylation differences consistent with maternal imprinting .

• Because about 5% of affected individuals inherit the SGCE pathogenic variant from their mothers , the apparent suppression of the M-D phenotype on maternal transmission of the SGCE allele is incomplete. In these instances, the phenotype may be milder. The reasons for loss of the maternal imprint are unknown.

Source: GeneReviews — "SGCE Myoclonus-Dystonia"

Diagnostic Criteria

Suggestive Findings

SGCE myoclonus-dystonia (SGCE-M-D) should be suspected in individuals with myoclonus alone or with dystonia that begins in the first or second decade of life. It less frequently presents with isolated dystonia. Recently suggested criteria for the diagnosis of M-D require four major criteria and no exclusionary criteria OR three major criteria, two minor criteria, and no exclusionary criteria .

Major criteria

• Myoclonus isolated or predominating over dystonia

• Prominence of the motor manifestations in the upper body

• Absence of truncal dystonia

• Positive family history

• Onset before age 18 years

Minor criteria

• Obsessive-compulsive disorder, anxiety-related disorder, or alcohol dependence

• Spontaneous remission of limb dystonia during childhood or adolescence

• Alcohol responsiveness

Source: GeneReviews — "SGCE Myoclonus-Dystonia"

Differential Diagnosis

Myoclonic dystonia 26 (OMIM 616398), associated with heterozygous pathogenic variants in KCTD17, is closest in phenotype to SGCE myoclonus-dystonia (SGCE-M-D). For further information about myoclonic dystonia 26 and other disorders to consider in the differential diagnosis of SGCE-M-D, see . Table 2. Other Genes of Interest in the Differential Diagnosis of SGCE Myoclonus-Dystonia

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with SGCE myoclonus-dystonia (SGCE-M-D) the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Clinical examination to evaluate the location, severity, and progression of dystonia and the severity and progression of myoclonus. This is best done by a neurologic specialist in movement disorders.

• Consultation with a clinical geneticist and/or genetic counselor.

Treatment of Manifestations

Medications may improve myoclonus and/or dystonia:

• While multiple anti-seizure medications have been reported in case series or individual reports, zonisamide is the first to demonstrate class I evidence of improvement of both myoclonus and dystonia in a double-blind study .

Valproate and levetiracetam may also be used. Topiramate and carbamazepine have been reported to improve myoclonus .

Source: GeneReviews — "SGCE Myoclonus-Dystonia"

Surveillance Guidelines

Table 3.

Recommended Surveillance for Individuals with Myoclonus-Dystonia

System/Concern | Evaluation | Frequency

Neurologic

| Neurologic exam to assess burden of myoclonus dystonia review therapy side effects | Annually

Psychiatric

| Eval for psychiatric features | Annually

Source: GeneReviews — "SGCE Myoclonus-Dystonia"