Myoclonus‐dystonia syndrome associated with Russell Silver syndrome

Abstract

Myoclonus-Dystonia Syndrome (MDS, DYT11) is a movement disorder characterized by myoclonus predominant in upper body regions and focal or segmental dystonia. MDS typically results from autosomal dominant loss-of-function mutations in the epsilon-sarcoglycan gene (SGCE) on chromosome 7q2112. We describe MDS due to maternal uniparental disomy of chromosome 7 (mUPD7) associated with Russell Silver Syndrome (RSS), rather than SGCE gene mutation. A 7-year-old girl with RSS presented for evaluation of involuntary movements of two years’ duration. Parents described generalized and multi-focal jerks of the head, limbs, and trunk, worsened by intercurrent illness and fatigue. The jerks sometimes resulted in accidental dropping or throwing of items. The involuntary movements were neither suppressible nor associated with premonitory sensation. Cognition, behavior, and mood were normal. Development was notable for mild gross and fine motor delays. The diagnosis of RSS was made at age 1 year based on intrauterine growth restriction, post-natal failure to thrive, and characteristic facial features. Microsatellite marker testing on the patient and her parents was indicative of maternal uniparental disomy for the entirety of chromosome 7. There was no known family history of similar symptoms. On examination, the patient was small for age with preserved head size (head circumference 50th%ile, length and weight <5th%ile). She had a triangular-shaped face, mild frontal bossing, scooped nasal bridge, small mouth, flat philtrum, and mild lower limb size asymmetry, all consistent with RSS. There was diffuse hypotonia with diminished muscle bulk, but full strength. Multifocal myoclonus was present at rest and worsened with action without stimulus sensitivity. The myoclonus was most prominent in the head, shoulders, torso, and upper extremities. Focal dystonia of the right upper extremity was elicited with prolonged writing. Dystonia was not evident in other body regions. Clinical evaluation included electroencephalogram, which showed generalized spike-wave discharges but no electrographic change during the periods of myoclonus. SGCE analysis did not identify any deletions. Treatment of the involuntary movements with medication was not pursued.