Objective: To identify and characterize the hereditary chorea other than Huntington’s disease (HD) in an Indian movement disorder clinic.

Background: Approximately 1-3% of HD phenotypes do not have the HTT mutation, making diagnosis challenging. Despite the growing number of genes linked to non-HD chorea, a considerable portion of cases remain undiagnosed.

Method: We retrospectively reviewed the movement disorder database of our institute to identify confirmed cases of hereditary chorea.

Results: There were 14 confirmed cases (8 males, 6 females) of non-HD hereditary chorea. We identified variants responsible for adult-onset chorea in VPS13A gene (n=4; chorea-acanthocytosis), ATN1 gene (n=1; DRPLA); ATXN2 gene (n=1, SCA 2); PPP2R2B gene (n=1, SCA12); NPC2 gene (n=1 Niemann-Pick disease Type-C) and GCDH gene (n=1; glutaric acidemia-I). The diagnoses in adolescent and childhood onset chorea included Wilson’s disease (WD; n=3), ADCY5 related dyskinesias (n=1) and benign hereditary chorea (BHC: variant NKX2-1 gene; n=1). Generalized chorea, significant behavioral abnormalities, cognitive impairment, and caudate atrophy similar to HD were observed in all 4 patients with VPS13A variant. The diagnostic clues were prominent oromandibular dystonia (4/4), neuropathy (3/4), seizure (2/4), head drops and axial hypotonia (1/4), high creatine kinase (4/4), acanthocytes in peripheral blood smear (3/4) and absence of family history. The DRPLA patient had a family history of anticipation and exhibited cognitive, motor, and psychiatric features similar to HD. The presence of significant myoclonus, seizures, ataxia, and cerebellar atrophy with white matter changes in MRI led to the suspicion of DRPLA. One patient each of SCA 2 and SCA 12 presenting as HD phenocopies; both had evidence of cerebellar dysfunction clinically and radiologically. Perioral dyskinesia and paroxysmal worsening of movements upon awakening from sleep characterized the ADCY5 variant. Infantile onset non-progressive chorea, recurrent pulmonary infection, and hypothyroidism prompted the diagnosis of BHC; the child had normal cognition and an MRI brain. WD patients showed K-F rings, prominent oromandibular dystonia, and characteristic brain MRI findings.

Conclusion: In our study, chorea-acanthocytosis was the most common cause of non-HD hereditary chorea. The identification of clinical, radiological, and lab characteristics can help narrow down the differential diagnoses.

References: 1. Schneider SA, Bird T. Huntington’s Disease, Huntington’s Disease Look-Alikes‎, and Benign Hereditary Chorea: What’s New? Mov Disord Clin Pract. 2016 Jan 27;3(4):342-354.
2. Termsarasab P. Chorea. Continuum (Minneap Minn). 2019 Aug;25(4):1001-1035.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/spectrum-of-non-hd-hereditary-chorea-case-series-from-an-indian-movement-disorder-centre/