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Background Myoclonus-dystonia is a movement disorder often associated with mutations in the maternally imprinted e-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.

Inverted duplications with terminal deletions have been reported in an increasing number of chromosomes and are probably more frequent than suspected until recently. We describe the cytogenetic and molecular characterization of an inverted duplication of chromosome 2p in an 8-year-old girl. Firstly interpreted as partial duplication 2p, the rearrangement was in fact an inverted duplication associated with a terminal deletion of the short arm of the rearranged chromosome 2, the latter not being detectable by cytogenetic analysis. The complete karyotype was: 46,XX,add(2)(p23)dn.ish inv dup del(2)(:p23.2p25.3::p25.3qter) (wcp2+,N-MYC++,2pter−)dn. We precisely define the extension of both the duplication and the deletion using bacterial artificial chromosomes clones spanning the regions. The size of the inverted duplicated segment was estimated to be 28 Mb, spanning from 2p23.2 to 2p25.3, and an approximately 1.6 Mb segment at 2pter-p25.3 was deleted in the abnormal chromosome. The physical findings noted in our patient include prominent forehead, hypertelorism, flat nasal bridge, and low-set and large ears. In addition, she had congenital heart defect and scoliosis. Her psychomotor development was severely delayed from the beginning. All these clinical features are the same as observed for the typical trisomy 2p23-pter syndrome. The phenotypic effects of the terminal deletion of 2p in addition to the trisomy are discussed. This is the third patient presenting with a severe clinical phenotype and a de novo inv dup del (2p). © 2007 Wiley-Liss, Inc.