Myoclonus-dystonia due to maternal uniparental disomy

Background: Myoclonus-dystonia is a movement disorder often associated with mutations in the maternally imprinted epsilon-sarcoglycan (SGCE) gene located on chromosome 7q21. Silver-Russell syndrome is a heterogeneous disorder characterized by prenatal and postnatal growth restriction and a characteristic facies, caused in some cases by maternal uniparental disomy of chromosome 7. Objectives: To describe and investigate the combination of a typical myoclonus-dystonia syndrome and Silver-Russell syndrome. Design: Clinical and neurophysiological examination as well as cytogenetic and molecular analyses. Setting: Movement disorder clinic. Patient: A 36-year-old man with typical myoclonus-dystonia and Silver-Russell syndrome. Main Outcome Measures: Clinical description of the disease and its genetic cause. Results: Cytogenetic analysis revealed mosaicism for a small chromosome 7 marker chromosome. Microsatellite analysis indicated loss of the paternal allele and maternal uniparental disomy of chromosome 7. In keeping with the maternal imprinting mechanism, no unmethylated allele of SGCE was detected after bisulfite treatment of the patient's DNA, and reverse transcription-polymerase chain reaction demonstrated loss of SGCE expression. Molecular analysis ruled out mutations in the SGCE gene. Conclusions: We identified a new genetic alteration maternal chromosome 7 disomy-that can cause myoclonus-dystonia. This alteration results in repression of both alleles of the maternally imprinted SGCE gene and suggests SGCE loss of function as the disease mechanism.