Growth charts for pontocerebellar hypoplasia type 2A

IntroductionPontocerebellar hypoplasia type 2A (PCH2A) is a rare, autosomal recessive disease, caused by a homozygous pathogenic variant in the gene TSEN54 (c.919G>A, p.A307S). Apart from the characteristic pontocerebellar hypoplasia in MRI, PCH2A is clinically characterized by a dyskinetic movement disorder, severe neurodevelopment delay, progressive microcephaly, and, less well recognized, failure to thrive. Additional symptoms such as seizures, gastrointestinal or respiratory problems are common. The aim of this study was to document growth data of PCH2A patients, calculate growth charts for height, weight, body mass index (BMI) and head circumference (hc), and compare these to German reference charts. Patients and methodsIn total, data of 65 patients with genetically confirmed PCH2A were included in the study. Growth data were collected retrospectively from medical reports and a parent questionnaire. Disease-specific growth charts were prepared using gamlss package in R. Sex-disaggregated growth charts for PCH2A were compared to German reference data from the KiGGs study. ResultsHeight and weight of patients with PCH2A were within the normal range at birth. Mean weight was significantly lower from the age of 3 months onwards, and mean height at the age of 6 months in patients with PCH2A, both, females and males. Mean BMI was statistically lower in patients at the age 4 months. Compared to reference values, mean head circumference of patients with PCH2A was significantly below average at birth, and all patients showed severe and progressive microcephaly in the further course. ConclusionIn line with previous reports, patients with PCH2A typically exhibit progressive microcephaly, and frequently fail to thrive during infancy. Disease-specific growth charts of pediatric patients with PCH2A are provided as a helpful tool to monitor height, weight, BMI and head circumference of affected children.