Objective: To describe cases referred to CETRAM suspected of Huntington’s disease (HD) according their phenotype, in whom an alternative diagnosis was proposed after ruling out this disease.

Background: HD is an AD neurodegenerative disorder, characterized mostly  by  chronic chorea, behavioral and cognitive impairment. About 1% of all cases with this phenotype do not have the HTT gene mutation. These cases are known as HD phenocopies [1, 2, 3].

Method: We reviewed the clinical records of  patients evaluated in CETRAM, between January 2016 and December 2019, using the words “Huntington”, “Chorea” and “Dementia” as a search criteria, selecting cases with HD phenotype. Additionally we reviewed our list of patients incorporated to the ENROLL-HD study, and those excluded from this data base due to a negative result in the genetic test for HD.

Results: A total of 157 patients were identified according to the search criteria, corresponding 150 to HD, 80 with genetic confirmatory test and 70 with compatible phenotype and family history of genetically confirmed HD. In 7 (4.4%) the genetic test was negative and no family history of HD was found. None of them had intermediate-sized CAG repeats in the HTT gene. The mean age of onset was 45.8 (33 to 65) years. The most remarkable family history was Chorea-acanthocytosis (1), CJD (1), dementia (3) and Psychiatric disorders (5). Comorbidities include epilepsy and cerebrovascular disease. Six patients presented Chorea, 3 of them with prominent buccolingual compromise. Two cases presented feeding dystonia and 1 focal hand dystonia, other movement disorders were reported. Cognitive and psychiatric compromise was reported in 6 and 5 cases respectively. In 2 unrelated patients Neuro-acanthocytosis was established (VPS13A mutation confirmed in 1 case), in 1 case familial dementia was suspected, and in 1 patient the diagnosis was unknown. We identified a possible secondary cause in 3 cases.

Conclusion: The proportion of cases with HD phenotype and negative result of the genetic test represents a slightly higher proportion compared to that reported in the literature [2, 3]. Secondary causes remain important in this group of patients, while Neuro-acanthocytosis represents the most common primary cause. It is necessary to improve access to genetic testing in Chile to try to specify the diagnosis in uncertain cases of HD phenocopies.

References: 1. McColgan P, Tabrizi SJ. Huntington’s disease: a clinical review. Eur J Neurol. 2018;25(1):24-34. doi:10.1111/ene.13413 2. Schneider SA, Bird T. Huntington’s Disease, Huntington’s Disease Look-Alikes‎, and Benign Hereditary Chorea: What’s New? Mov Disord Clin Pract. 2016;3(4):342-354. doi:10.1002/mdc3.12312 3. E.J. W, S.J. T. Huntington’s disease phenocopy syndromes. Curr Opin Neurol. 2007;20(6):681-687. doi:10.1097/WCO.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-of-cases-with-huntingtons-disease-phenotype-and-negative-genetic-test-for-huntingtin-mutations-in-the-center-for-movement-disorders-cetram-in-chile/