Expanding the phenotype of SCA19/22: Parkinsonism, cognitive impairment and epilepsy

TL;DR

This study expands the known clinical features of SCA19/22, revealing associations with Parkinsonism, cognitive impairments, and epilepsy, linked to KCND3 mutations, based on detailed family case analyses.

Contribution

It introduces new clinical features and cognitive profiles associated with SCA19/22, highlighting KCND3 as a candidate gene for diverse neurological symptoms.

Findings

Broadened phenotypic spectrum of SCA19/22 includes Parkinsonism and epilepsy.

Identified KCND3 mutation in families with diverse neurological features.

Documented cognitive impairments, including visuospatial deficits, in SCA19/22 patients.

Abstract

BACKGROUND: Spinocerebellar ataxia types 19 and 22 (SCA19/22) are rare conditions in which relatively isolated cerebellar involvement is frequently associated with cognitive impairment. Here, we report on new clinical features and provide details of the cognitive profile in two SCA19/22 families.METHODS: Two families displaying an autosomal-dominant form of cerebellar ataxia underwent clinical examinations and genetic testing.RESULTS: In addition to the classical clinical features of SCA, a wide spectrum of cognitive disorders (including visuospatial impairments) was observed. Eight patients had mild Parkinsonism, and five had epilepsy. Genetic testing showed that the KCND3 mutation (c.679_681delTTC, p.F227del) was present in both families.CONCLUSIONS: Our findings broaden the phenotypic spectrum of SCA19/22, and suggest that KCND3 should be included in the list of candidate genes for epilepsy, Parkinsonism and cognitive impairment.