Multisystemic Involvement in Autosomal Recessive Cerebellar Ataxia Type 8 Having a Novel SYNE1 Nonsense Variant

Autosomal recessive cerebellar ataxia type 8 (SCAR8) is a neurodegenerative disorder caused by variants of the SYNE1 gene. It presents with progressive cerebellar ataxia, and some patients exhibit multisystemic symptoms. A 33-year-old woman had cerebellar ataxia since childhood, motor neuron disease, vocal cord abduction paralysis, joint deformities, oculocutaneous telangiectasia, and obesity, and required a tracheostomy. Whole-exome sequencing revealed compound heterozygous nonsense variants of SYNE1 (NM_033071.5), including the novel variant c.18727C>T (p.Gln6243Ter). The SYNE1 mRNA expression was reduced by 23% relative to that in the controls. A literature review, including this case, revealed that SYNE1 variants tend to cluster in the C-terminal region in patients with respiratory dysfunction.