Pontocerebellar hypoplasia: Genes and phenotypes

Pontocerebellar Hypoplasia (PCH) is a rare heterogeneous group of neurodegenerative disorders, often with a prenatal onset. Patients have severe hypoplasia or atrophy of cerebellum and pons, with variable involvement of supratentorial structures. Although clinical and neuroradiological features are variable, most patients suffer from severe motor and cognitive impairments. PCH often leads to death during infancy. Based on distinct clinical features and genetic causes, current classification comprises eleven types of PCH. This thesis focuses on the identification of novel disease genes and the description of new phenotype-genotype correlations in PCH. In addition, the neuroradiological features of the most frequent subtypes of PCH (PCH1B/PCH2A) are studied in detail. The expression patterns of the PCH related genes in the developing and adult brain will be shortly discussed in an effort to explain the specific cerebellar involvement in PCH. Finally, the clinical applicability of the ever expanding PCH classification, which now includes a large variety of phenotypes, will be considered.