The Two Faces of Pediatric SCA2.

Area of Science:

• Neurology
• Genetics
• Pediatrics

Background:

• Spinocerebellar ataxia type 2 (SCA2) is typically an adult-onset autosomal dominant neurodegenerative disorder.
• Expanded CAG repeats in the ATXN2 gene are associated with pediatric onset of SCA2.
• The natural history of pediatric SCA2 has not been comprehensively described.

Purpose of the Study:

• To describe the natural history and clinical characteristics of spinocerebellar ataxia type 2 (SCA2) in pediatric patients.
• To identify distinct phenotypic groups within pediatric SCA2.
• To establish genetic parameters differentiating these groups.

Main Methods:

• Analysis of clinical and genetic data from 22 pediatric SCA2 patients across 17 institutions.
• Comparison with 20 previously reported pediatric SCA2 cases.
• Genetic analysis focused on CAG repeat size in the ATXN2 gene.

Main Results:

• Pediatric SCA2 exhibits a bimodal phenotype: an infantile group (n=9) with developmental delay, seizures, and atrophy, and a juvenile group (n=13) resembling adult-onset SCA2.
• A CAG repeat threshold of 88±4 in ATXN2 distinguished the infantile from the juvenile group.
• SCA2 was maternally inherited in 22% of cases, including three infantile presentations, and was independent of parental origin.

Conclusions:

• Pediatric SCA2 has a recognizable bimodal phenotypic spectrum, distinct from the continuous spectrum of SCA7.
• Targeted analysis of ATXN2 CAG repeat number facilitates diagnosis of pediatric SCA2.
• Genetic counseling should address the significant rate of maternal transmission in pediatric SCA2.