Edward J. Wild and Ese E. Mudanohwo contributed equally to this work as first authors.
Huntington's disease phenocopies are clinically and genetically heterogeneous
Article first published online: 7 JAN 2008
Copyright © 2008 Movement Disorder Society
Volume 23, Issue 5, pages 716–720, 15 April 2008
How to Cite
Wild, E. J., Mudanohwo, E. E., Sweeney, M. G., Schneider, S. A., Beck, J., Bhatia, K. P., Rossor, M. N., Davis, M. B. and Tabrizi, S. J. (2008), Huntington's disease phenocopies are clinically and genetically heterogeneous. Mov. Disord., 23: 716–720. doi: 10.1002/mds.21915
- Issue published online: 24 APR 2008
- Article first published online: 7 JAN 2008
- Manuscript Accepted: 21 NOV 2007
- Manuscript Received: 14 JUN 2007
- High Q Foundation, Inc.
- Brain Research Trust, UK
- Huntington's disease (HD);
- familial prion disease;
Huntington's disease (HD) classically presents with movement disorder, cognitive dysfunction and behavioral problems but is phenotypically variable. One percent of patients with HD-like symptoms lack the causative mutation and are considered HD phenocopies. Genetic diseases known to cause HD phenocopies include HD-like syndromes HDL1, HDL2, and HDL4 (SCA17). HD has phenotypic overlap with dentatorubral-pallidoluysian atrophy, the spinocerebellar ataxias and neuroferritinopathy. Identifying the genetic basis of HD phenocopies is important for diagnosis and may inform the search for HD genetic modifiers. We sought to identify neurogenetic diagnoses in the largest reported cohort of HD phenocopy patients. Two hundred eighty-five patients with syndromes consistent with HD, who were HD expansion-negative, were screened for mutations in PRNP, JPH3, TBP, DRPLA, SCA1, SCA2, SCA3, FTL and FRDA. Genetic diagnoses were made in 8 subjects: we identified 5 cases of HDL4, 1 of HDL1 and 1 of HDL2. One patient had Friedreich's ataxia. There were no cases of DRPLA, SCA1, SCA2, SCA3, or neuroferritinopathy. HD phenocopies are clinically and genetically diverse and a definitive genetic diagnosis is currently possible in only a minority of cases. When undertaken, it should be clinically directed and patients and clinicians should be prepared for the low probability of reaching a genetic diagnosis in this group of patients. © 2008 Movement Disorder Society