title: Myoclonus-dystonia and Silver-Russell syndrome resulting from maternal uniparental disomy of chromosome 7.
abstract: Myoclonus-dystonia (M-D) is a movement disorder that is often associated with mutations in epsilon-sarcoglycan (SGCE), a maternally imprinted gene at 7q21.3. We report a 24-year-old male with short stature (<5th percentile) and a movement disorder clinically consistent with M-D. Single nucleotide polymorphism (SNP) array did not identify significant copy number changes, but revealed three long continuous stretches of homozygosity on chromosome 7 suggestive of uniparental disomy. Parental SNP arrays confirmed that the proband had maternal uniparental disomy of chromosome 7 (mUPD7) with regions of heterodisomy and isodisomy. mUPD7 is the cause of approximately 5-10% of Silver-Russell syndrome (SRS), a disorder characterized by prenatal and postnatal growth retardation. Although SRS was not suspected in our patient, these findings explain his short stature. SGCE methylation testing showed loss of the unmethylated paternal allele. Our findings provide a unifying diagnosis for his short stature and M-D and help to optimize his medication regimen. In conclusion, we show that M-D is a clinical feature that may be associated with SRS due to mUPD7. Individuals with mUPD7 should be monitored for the development of movement disorders. Conversely, individuals with M-D and short stature should be evaluated for SRS.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Sheridan
authors.forename: A
authors.initials: A
authors.lastname: Bytyci Telegrafi
authors.forename: V
authors.initials: V
authors.lastname: Stinnett
authors.forename: C C
authors.initials: CC
authors.lastname: Umeh
authors.forename: Z
authors.initials: Z
authors.lastname: Mari
authors.forename: T M
authors.initials: TM
authors.lastname: Dawson
authors.forename: J
authors.initials: J
authors.lastname: Bodurtha
authors.forename: D A S
authors.initials: DA
authors.lastname: Batista
mesh_terms: D000483:Alleles; D002897:Chromosomes, Human, Pair 7; D018899:CpG Islands; D019175:DNA Methylation; D020821:Dystonic Disorders / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D049031:Sarcoglycans / Q000235:genetics; D056730:Silver-Russell Syndrome / Q000235:genetics*; D024182:Uniparental Disomy; D055815:Young Adult
chemical_list: C526572:SGCE protein, human; D049031:Sarcoglycans