An array of various phenocopies with multiple etiologies that are not associated with the main chromosomal mutation responsible forHuntington’s disease (HD) can also produce HD symptoms, according to a study reported inJAMA Neurology.1
The primary cause of HD is a trinucleotide repeat expansion of the HTT gene in excess of 35 units, although a large number of other genes have also been suspected to contribute.2 To investigate these possible variants, the investigators performed a genetic evaluation of 226 patients referred to the French National Huntington Disease Reference Centre For Rare Diseases who had been identified as having HD phenotypes. The CAG repeat HTT expansion considered pathologic of HD was confirmed in 198 patients, and was absent in the remaining 28 patients who were classified as having HD-like (HDL) disease.
Louise-Laure Mariani, MD, of the Assistance Publique–Hôpitaux de Paris, Pitié-Salpêtrière University Hospital in Paris, France, and colleagues used a combination of clinical and genetic approaches to identify responsible genes from a panel of 63 potential candidate phenocopies, which were then matched to 10 of the 28 patients (35.7%) with HDL. Eight of those had family histories consistent with HD, including a combination of movement disorders and psychological symptoms. Cognitive patterns were similar across all variants, with more pronounced subcortical dementia in the HD-HTT group compared to the others.