ATP1A3variants and slowly progressive cerebellar ataxia without paroxysmal or episodic symptoms in children

A heterogeneous spectrum of clinical manifestations caused by mutations inATP1A3have been previously described. Here we report two cases of infantile-onset cerebellar ataxia, due to two differentATP1A3variants. Both patients showed slowly progressive cerebellar ataxia without paroxysmal or episodic symptoms. Brain magnetic resonance imaging revealed mild cerebellar cortical atrophy in both patients. Whole exome sequencing revealed a de novo heterozygous variant inATP1A3in both patients. One patient had the c.460A>G (p.Met154Val) variant, while the other carried the c.1050C>A (p.Asp350Lys) variant. This phenotype was characterized by a slowly progressive cerebellar ataxia since the infantile period, which has not been previously described in association withATP1A3variants or inATP1A3-related clinical conditions. Our report contributes to extend the phenotypic spectrum ofATP1A3mutations, showing paediatric slowly progressive cerebellar ataxia with mild cerebellar atrophy alone as an additional clinical presentation ofATP1A3-related neurological disorders.

Automated summary

This study reports two cases of infantile-onset cerebellar ataxia caused by mutations in the ATP1A3 gene, showing slowly progressive symptoms with mild cerebellar cortical atrophy. This phenotype, characterized by slowly progressive cerebellar ataxia since infancy, has not been previously described in association with ATP1A3 variants or related clinical conditions.