What’s new in pontocerebellar hypoplasia? An update on genes and subtypes

Tessa van Dijk,
Frank Baas,
Peter G. Barth and
Bwee Tien Poll-TheEmail author View ORCID ID profile

Orphanet Journal of Rare Diseases201813:92

https://doi.org/10.1186/s13023-018-0826-2

Received: 29 November 2017

Accepted: 16 May 2018

Published: 15 June 2018

Abstract

Background

Pontocerebellar hypoplasia (PCH) describes a rare, heterogeneous group of neurodegenerative disorders mainly with a prenatal onset. Patients have severe hypoplasia or atrophy of cerebellum and pons, with variable involvement of supratentorial structures, motor and cognitive impairments. Based on distinct clinical features and genetic causes, current classification comprises 11 types of PCH.

Main text

In this review we describe the clinical, neuroradiological and genetic characteristics of the different PCH subtypes, summarize the differential diagnosis and reflect on potential disease mechanisms in PCH. Seventeen PCH-related genes are now listed in the OMIM database, most of them have a function in RNA processing or translation. It is unknown why defects in these apparently ubiquitous processes result in a brain-specific phenotype.

Conclusions

Many new PCH related genes and phenotypes have been described due to the appliance of next generation sequencing techniques. By including such a broad range of phenotypes, including non-degenerative and postnatal onset disorders, the current classification gives rise to confusion. Despite the discovery of new pathways involved in PCH, treatment is still symptomatic. However, correct diagnosis of PCH is important to provide suitable care and counseling regarding prognosis, and offer appropriate (prenatal) genetic testing to families.