Genetic Brief Three Brothers With a Very-Late-Onset Writer’s Cramp Roongroj Bhidayasiri, MD, MRCP(UK), 1,2 * Joanna C. Jen, MD, PhD, 1 and Robert W. Baloh, MD 1 1 Department of Neurology, UCLA Medical Center, Geffen School of Medicine, University of California, Los Angeles, California, USA 2 Division of Neurology, Chulalongkorn University Hospital, Bangkok, Thailand Abstract: Writer’s cramp (WC) is a form of focal task-specific dystonia, which is brought on by writing. Although most cases are sporadic, a positive family history is present in 5% to 20% of cases. To date, WC has been reported in several families with primary torsion dystonia, including DYT7, a pure focal dystonia, and in the mixed dystonias, DYT1, DYT6, and DYT13. We describe a family of Bulgarian descent with three brothers presenting with a very-late-onset dystonic WC, com- patible with linkage to chromosome 18p. © 2005 Movement Disorder Society Key words: writer’s cramp; focal task-specific dystonia; DYT7 Primary torsion dystonia (PTD) is a clinically and genetically heterogeneous movement disorder in which dystonia is the primary and sole abnormality directly attributed to the condition. Although most cases of late- onset PTD are sporadic, there is increasing evidence that late-onset PTD is genetically more complex than early- onset PTD and appears to have an autosomal dominant inheritance with reduced penetrance. To date, only one locus for pure focal dystonia, DYT7, and two loci for the mixed dystonias, DYT6 and DYT13, have been identi- fied. 1–3 Recently, early-onset myoclonus-dystonia (DYT11) in a Canadian family was mapped to chromo- some 18p. 4 New families with late-onset PTD are im- portant because the condition appears to be genetically heterogeneous. We describe a family of Bulgarian de- scent with three brothers presenting with a very-late- onset dystonic writer’s cramp (WC), compatible with linkage to chromosome 18p. PATIENTS AND METHODS Consenting family members underwent a standardized neurological examination and DNA analysis. The study was approved by the UCLA institutional review board. Genotyping DNA was extracted from peripheral blood leukocytes using standard techniques. Genomic amplification was performed using fluorescent-labeled microsatellite mark- ers spanning the critical regions on chromosome 8 [DYT6; MIM 602629; D8S260, D8S533, D8S530 (flanked by D8S2323 and D8S279), D8S1705], 18 (DYT7; MIM 602214; D18S481, D18S52, D18S976, GATA185C06, D18S391, D18S967), and 1 (DYT13; MIM 607671; D1S468, D1S1612, D1S1597, D1S3669, D1S552). We sequenced the -sarcoglycan (SGCE) gene on chromosome 7 (myoclonus-dystonia or DYT11, MIM 159900) 5 and tested for the GAG deletion on chromo- some 9, commonly seen in DYT1 (MIM 605204). 6 RESULTS Case Reports Clinical examination of four non-Ashkenazi Jewish siblings showed that three had symptoms of late-onset writer’s cramp, two associated with postural tremor. *Correspondence to: Dr. Roongroj Bhidayasiri, Department of Neu- rology, Reed Neurological Research Institute, UCLA Medical Center, 710 Westwood Plaza, Los Angeles, CA 90095. E-mail: rbh@ucla.edu Received 8 November 2004; Revised 16 January 2005; Accepted 21 January 2005 Published online 13 June 2005 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20568 Movement Disorders Vol. 20, No. 10, 2005, pp. 1375–1377 © 2005 Movement Disorder Society 1375