Multisystemic Involvement in Autosomal Recessive Cerebellar Ataxia Type 8 Having a Novel SYNE1 Nonsense Variant.
Shoko Hongo, Takuya Konno, Yuya Hatano et al.
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Case in brief
A 33-year-old woman with childhood-onset cerebellar ataxia developed a broad range of additional findings, including motor neuron disease, vocal cord abduction paralysis, joint deformities, oculocutaneous telangiectasia, and obesity; she required tracheostomy. Whole-exome sequencing identified compound heterozygous nonsense variants in SYNE1, including c.18727C>T (p.Gln6243Ter), reported as novel. SYNE1 mRNA expression was 23% lower than in controls. The report diagnosed autosomal recessive cerebellar ataxia type 8 and noted, in a literature review including this case, a tendency for SYNE1 variants in patients with respiratory dysfunction to cluster in the C-terminal region.
What made this case unusual
The combination of multisystem findings—including motor neuron disease and vocal cord abduction paralysis requiring tracheostomy—extended beyond the progressive cerebellar ataxia typically described for this disorder.
Diagnostic / clinical pearl
In a patient with cerebellar ataxia and respiratory or other multisystem involvement, SYNE1-related disease may be relevant; genetic testing can identify compound heterozygous variants.
Why it matters
The reported tendency for variants to cluster in the C-terminal region among patients with respiratory dysfunction may help frame genotype–phenotype assessment, although this case and review do not establish causation.