Genetic Causes of early onset Ataxia: Experience from the National Sheffield Paediatric Ataxia Centre

Abstract

AbstractEarly onset cerebellar ataxias are sufficiently distinct in aetiology and disease course from adult onset ataxias to warrant independent evaluation. It has long been assumed that complex (multisystem) ataxias are more frequent in the paediatric ataxia population but the proportion of genetic causes and the makeup of this group of patients has not previously been examined in detail.Data from 704 patients from the Sheffield Paediatric Ataxia Centre (SPAC) confirms Friedriech’s ataxia as the most common genetic paediatric ataxia (25%) but this is closely followed byCACNA1Amutations (18.2%). Pick up rate was higher than for adult populations and recessive and dominant conditions were represented in roughly equal proportions. A large proportion of mutations were only found in a single gene and nearly half of the NGS variants identified (46.7%) were variants of unknown significance (VUS). In total 13.8% of this population had a genetic cause confirmed. This demonstrates the utility of large gene panel testing in the paediatric ataxia population and highlights the need for further research and developments into determination of the pathogenicity of genetic variants.In conclusion, simple mendelian genetic diseases are responsible for a significant proportion of cases of chronic ataxia in the paediatric cohort.