Georgios Koutsis1, Georgia Karadima2, Athina Kladi2, Marios Panas2. 1. Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece. Electronic address: gkoutsi2@otenet.gr. 2. Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece.
Abstract
OBJECTIVE: To address diagnostic and prognostic issues in patients with late-onset Huntington's disease (HD). METHODS: We analyzed a cohort of 41 late-onset (≥60 years) HD patients and compared them to 39 late-onset patients referred for HD testing that were negative for the HD-expansion and to 290 usual-onset (20-59 years) HD patients. Disease severity was assessed by the Total Functional Capacity Scale. RESULTS: Late-onset HD comprised 11.5% of our HD cohort. In total, 70.7% of late-onset HD patients had positive family history compared to 15.4% of late-onset expansion-negative patients (p < 0.001). Clinical features at onset or presentation could not usefully distinguish between late-onset expansion-positive and negative patients, excepting hemichorea, which was absent from the HD group (p = 0.024). Chorea was the first clinical feature in 53.7% and a presenting feature in 90.2% of late-onset HD. The mutation hit rate for late-onset patients was 51.3%, lower than in usual-onset patients (p = 0.04). Frequencies of chorea, cognitive impairment and psychiatric manifestations at onset or presentation were not significantly different between late-onset and usual-onset HD patients. Gait unsteadiness however was more common at presentation in late-onset HD (p = 0.007). Late-onset HD patients reached a severe stage of illness on average 2.8 years earlier than usual-onset HD patients (p = 0.046). CONCLUSIONS: A positive family history suggestive of HD, although absent in a third of patients, remains a helpful clue in diagnosing late-onset HD. Prognosis of late-onset HD in terms of Total Functional Capacity appears no better and shows a trend of being somewhat less favorable compared to usual-onset HD.
OBJECTIVE: To address diagnostic and prognostic issues in patients with late-onset Huntington's disease (HD). METHODS: We analyzed a cohort of 41 late-onset (≥60 years) HDpatients and compared them to 39 late-onset patients referred for HD testing that were negative for the HD-expansion and to 290 usual-onset (20-59 years) HDpatients. Disease severity was assessed by the Total Functional Capacity Scale. RESULTS: Late-onset HD comprised 11.5% of our HD cohort. In total, 70.7% of late-onset HDpatients had positive family history compared to 15.4% of late-onset expansion-negative patients (p < 0.001). Clinical features at onset or presentation could not usefully distinguish between late-onset expansion-positive and negative patients, excepting hemichorea, which was absent from the HD group (p = 0.024). Chorea was the first clinical feature in 53.7% and a presenting feature in 90.2% of late-onset HD. The mutation hit rate for late-onset patients was 51.3%, lower than in usual-onset patients (p = 0.04). Frequencies of chorea, cognitive impairment and psychiatric manifestations at onset or presentation were not significantly different between late-onset and usual-onset HDpatients. Gait unsteadiness however was more common at presentation in late-onset HD (p = 0.007). Late-onset HDpatients reached a severe stage of illness on average 2.8 years earlier than usual-onset HDpatients (p = 0.046). CONCLUSIONS: A positive family history suggestive of HD, although absent in a third of patients, remains a helpful clue in diagnosing late-onset HD. Prognosis of late-onset HD in terms of Total Functional Capacity appears no better and shows a trend of being somewhat less favorable compared to usual-onset HD.
Authors: Melissa A Holman; John Quillin; Timothy P York; Claudia M Testa; Ami R Rosen; Virginia W Norris Journal: J Genet Couns Date: 2018-02-20 Impact factor: 2.537