A Novel Co‐existence of Spinocerebellar Ataxia 1 and Spinocerebellar Ataxia 2 Mutations in Indian Patients

Abstract

BackgroundBackground: Spinocerebellar ataxia 1 (SCA1) and SCA2 are dominantly inherited ataxias caused due to CAG expansion mutation in ATXN1 (CAG≥39) and ATXN2 (CAG≥32) genes located at 6p22.3 and 12q24.12 loci, respectively, with key manifestations of progressive limb and gait ataxia and with or without brain stem and pyramidal tract involvement. Both SCA1 and SCA2 are quite prevalent subtypes among the SCAs. There are very few reports that describe a combinatorial SCA subtype mutation in a single patient. Cases Cases: Here, we report a novel co-occurrence of SCA1 and SCA2 mutations in two unrelated patients. Case-1 was observed to carry ATXN1-CAG (30/40) and ATXN2-CAG (23/45), while case-2 harbored ATXN1-CAG (29/42) and ATXN2-CAG (23/41). Overall, the clinical outcome was complex with probable early onset than expected in Case-1 and in Case-2, we observed a significant delayed onset of the disease than expected. Conclusion Conclusion:These cases highlight the probabilistic interactive outcome of two unrelated genetic events towards a converging phenotype. Case Series Case 1A 25 year old male (Fig. 1A: III:3) presented in our clinic with a history of gait ataxia for the past 10 years (AO: 15 years). The patient reported no history of alcohol, smoking, or any other substance abuse. The patient gradually developed slurred speech and upper limb in-coordination within the next 5 years of disease progression (AO: 20 years). There were no signs of visual, sensory, hearing impairment or psychogenic symptoms experienced by the patient. Cerebellar signs like gait ataxia, impaired finger to nose test, impaired heel to shin test, dysarthria, dysdiadochokinesia and slow saccades were assessed during clinical assessment of the patient. The patient did not show any symptoms of fasciculation, broken pursuits, nystagmus, dysphasia, tremor and dementia but had complaints of excessive sleep. His mini mental state examination (MMSE) score was 30.