American Journal of Medical Genetics 121A:31–36 (2003) Clinical Report Myoclonus in a Patient With a Deletion of the e-Sarcoglycan Locus on Chromosome 7q21 Ralph J. DeBerardinis, 1 Danielle Conforto, 1 Karen Russell, 1 Jennifer Kaplan, 2 Peter R. Kollros, 3 Elaine H. Zackai, 1 and Beverly S. Emanuel 1 * 1 Department of Pediatrics, Division of Human Genetics and Molecular Biology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 2 Division of Neonatology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 3 Abington Pediatric Neurologic Consultants, 1941 Woodland Avenue, Abington, Pennsylvania Autosomal dominant myoclonus-dystonia syndrome (MDS) is characterized by myoclo- nic and/or dystonic movements with onset as early as infancy. In most families, MDS is caused by mutations in the gene SGCE, which encodes e-sarcoglycan and is located on chromosome 7q21. Data from several sources, including multi-generation pedi- grees revealing parent-of-origin effects on MDS penetrance, suggest that SGCE is ma- ternally imprinted. We present a 32-month- old patient with an interstitial deletion affecting chromosome 7q21, and a phenotype including myoclonus, microcephaly, short stature, dysmorphic face and language delay. We used fluorescence in situ hybridi- zation (FISH) to estimate the size of our patient’s deletion (9.0–15 Mbp) and to con- firm absence of SGCE on the affected chro- mosome. Polymerase chain reaction (PCR) analysis of polymorphic markers in the region revealed that the paternally inher- ited chromosome contained the deletion, consistent with a model of maternal SGCE imprinting. Our patient is the first case of MDS caused by complete deletion of SGCE, and represents a new contiguous gene dis- order. The case underscores the need to consider chromosomal deletions in patients whose phenotypes are more complex than the classic presentation of a known disease. ß 2003 Wiley-Liss, Inc. KEY WORDS: chromosome deletion syn- drome; myoclonus; SGCE; imprinting; fluorescence in situ hybridization INTRODUCTION Essential myoclonus is an uncommon condition char- acterized by abrupt muscle contractions, usually of the neck and upper arms, with onset within the first two decades of life. The contractions are exacerbated by purposeful movements, last less than 1 sec, and are not accompanied by EEG changes. Although they general- ly have a benign course, establishing control over the contractions with standard antiepileptic medications is difficult or impossible. Classically, patients have achiev- ed the best response by drinking alcohol [reviewed in Quinn, 1996]. A familial form of essential myoclonus has been well described [e.g., Quinn and Marsden, 1984; reviewed in Gasser, 1998]. Kyllerman et al. [1990] reported a large family with more than 20 members affected by an autosomal dominant form of myoclonus. Subsequent studies identified many other families with a similar pattern of inheritance [Klein et al., 1999, 2000; Nygaard et al., 1999; Vidailhet et al., 2001; Zimprich et al., 2001]. In these families, affected individuals generally had myoclonus with or without dystonic movements of the limbs or trunk. The association of myoclonus and dystonia in some individuals or within the same family led to use of the term myoclonus-dystonia syndrome (MDS). MDS is a genetically heterogeneous disorder. Linkage analysis on one 30-member family first established an MDS locus on chromosome 11q23. In that family, the disease cosegregated with a missense mutation (V154I) Grant sponsor: NIH; Grant numbers: HD26979, GM58759. *Correspondence to: Beverly S. Emanuel, Chief, Division of Human Genetics and Molecular Biology, 1002 Abramson Research Center, The Children’s Hospital of Philadelphia, 34th St and Civic Center Boulevard, Philadelphia PA, 19104. E-mail: beverly@mail.med.upenn.edu Received 7 November 2002; Accepted 22 January 2003 DOI 10.1002/ajmg.a.20162 ß 2003 Wiley-Liss, Inc.