Case Report: Late-Onset Autosomal Recessive Cerebellar Ataxia Associated With SYNE1 Mutation in a Chinese Family

Abstract

Autosomal recessive cerebellar ataxia type 1 (ARCA-1), also known as autosomal recessive spinocerebellar ataxia type 8 (SCAR8), is caused by spectrin repeat containing nuclear envelope protein 1 (SYNE1) gene mutation. Nesprin-1, encoded by SYNE1, is widely expressed in various tissues, especially in the striated muscle and cerebellum. The destruction of Nesprin-1 is related to neuronal and neuromuscular lesions. It has been reported that SYNE1 gene variation is associated with Emery-Dreifuss muscular dystrophy type 4, arthrogryposis multiplex congenita, SCAR8, and dilated cardiomyopathy. The clinical manifestations of SCAR8 are mainly characterized by relatively pure cerebellar ataxia and may be accompanied by upper and/or lower motor neuron dysfunction. Some affected people may also display cerebellar cognitive affective syndrome. It is conventionally held that the age at the onset of SCAR8 is between 6 and 42 years (the median age is 17 years). Here, we report a pedigree with SCAR8 where the onset age in the proband is 48 years. This case report extends the genetic profile and clinical features of SCAR8. A new pathogenic site (c.7578del; p.S2526Sfs*8) located in SYNE1, which is the genetic cause of the patient, was identified via whole exome sequencing (WES).

Autosomal Recessive Cerebellar Ataxias: New Acronyms, Old Eponyms, and the Butterfly Life Cycle

“…8 Since this, the disease was alternatively labeled SYNE1 ataxia, autosomal recessive spinocerebellar ataxia type 8 (SCAR8), or autosomal recessive cerebellar ataxia 1 (ARCA 1). 8 The clinical features range from a pure cerebellar form, including late-onset ataxia, 27 to cerebellar ataxia plus syndrome associated with saccadic slowing, pyramidal signs (spastic ataxia or complicated hereditary spastic paraplegia), 28 and lower motor neuron signs, among others. 29 Thus, the designation Beauce's ataxia became inexact, and the wide spectrum of clinical manifestations is best defined using the term SYNE1-spectrum disorders.…”