We describe a case of medically-refractory Myoclonus Dystonia Syndrome (MDS) caused by maternal uniparental disomy of chromosome 7 (mUPD7) associated with Russell-Silver syndrome (RSS), which responded well to bilateral GPi DBS.

MDS is classically associated with autosomal dominant mutations in the epsilon-sarcoglycan gene (SGCE) on chromosome 7q21.3. Rarely, it may result from mUPD7 associated with RSS, a condition characterized by prenatal and postnatal growth restriction and dysmorphic features. Patients with medically-refractory MDS caused by SGCE mutation have been successfully treated with GPi DBS^1,2. DBS has never been reported in a patient suffering from MDS secondary to mUPD7.

An 18-year-old right-handed female with a history of RSS presented with dysmorphic features consistent with RSS, generalized, action-induced myoclonus, and generalized dystonia. SNP array showed two segments of homozygosity on chromosome 7, suggesting uniparental disomy which was confirmed by PCR-based microsatellite marker analysis of the patient and her parents. SGCE sequence and del/dup testing revealed an absence of mutations.

The patient tried multiple medications, including levetiracetam, clonazepam, and tetrabenazine, but symptoms persisted and severely limited her functional ability. She underwent DBS surgery targeting bilateral GPi, with significant improvement in her total Unified Myoclonus Rating Scale score (208 pre-DBS to 16 at 4 months post-DBS) and total Burke-Fahn-Marsden Dystonia Rating Scale score (47 pre-DBS to 11). Furthermore, her SF-36 scores rose significantly, indicating improvement in her post-surgical functional status.

MDS is associated with autosomal dominant loss-of-function mutations in SGCE on chromosome 7q21.3, a maternally imprinted (silenced) gene. mUPD7 may cause the MDS phenotype due to lack of expression of SGCE in the absence of a paternal allele^3-5. Our patient showed significant improvement in both objective measures of myoclonus and dystonia, and in self-reported quality of life after surgery.

This is the first described case of medically-refractory MDS caused by mUPD7 treated successfully with DBS.