A novel Syne 1 gene mutation in several members of a Turkish family

Abstract

Background: Autosomal recessive cerebellar ataxia due to SYNE1 is a multisystem neurodegenerative disease with features including upper and lower motor neuron signs, respiratory failure, and mental retardation in addition to relatively slowly progressive cerebellar ataxia.

Methods: Case presentation Results: A 73-year-old male patient presented to our clinic with a history of progressive balance problems and recurrent falls over the past 45 years. His family history is notable for consanguinity, with two brothers and two cousins exhibiting similar neurological symptoms. The patient also has a history of the death of his three children, two of whom passed away at birth and one at 20 days of age. He currently has one son and two healthy daughters. In his neurological exam, he was wheelchair-bound and could barely walk due to severe ataxia. He also had cerebellar dysarthria and tongue atrophy. Reflexes in the upper extremities were bilaterally hyperactive, with a positive palmomental reflex. Fasciculations were noted in the left arm, which also exhibited atrophy when compared to the right, with a 1 cm diameter difference. Additional findings included a pes cavus deformity of the right foot, and flexor plantar reflexes. Brain MRI showed significant cerebellar atrophy, with prominent global cortical atrophy. There was no evidence of polyneuropathy in EMG. Given that clinical findings consistent with cerebellar ataxia along with a positive family history of similar symptoms suggested a potential hereditary ataxia syndroms, we ordered genetic testing. His WES analysis revealed a novel homozygous SYNE1 c.6444del p.Gly2149GlufsTer8 -Exon44-variant.