Autosomal recessive spinocerebellar ataxia SCAR8/ARCA1: first families detected in Spain

Abstract

Abstract Introduction Autosomal recessive spinocerebellar ataxia type 8 (ARCA1/SCAR8) is caused by mutations of the SYNE1 gene. The disease was initially described in families from Quebec (Canada) with a phenotype of pure cerebellar syndrome, but in recent years has been reported with a more variable clinical phenotype in other countries. Cases have recently been described of muscular dystrophy, arthrogryposis, and cardiomyopathy due to SYNE1 mutations. Objective To describe clinical and molecular findings from 4 patients (3 men and one woman) diagnosed with ARCA1/SCAR8 from 3 Spanish families from different regions. Material and methods We describe the clinical, paraclinical, and genetic results from 4 patients diagnosed with ARCA1/SCAR8 at different Spanish neurology departments. Results Onset occurred in the third or fourth decade of life in all patients. After 15 years of progression, 3 patients presented pure cerebellar syndrome, similar to the Canadian patients; the fourth patient, with over 30 years’ progression, presented vertical gaze palsy, pyramidal signs, and moderate cognitive impairment. In all patients, MRI studies showed cerebellar atrophy. The genetic study revealed distinct pathogenic SYNE1 mutations in each family. Conclusions ARCA1/SCAR8 can be found worldwide and may be caused by many distinct mutations in the SYNE1 gene. The disease may manifest with a complex phenotype of varying severity.