PONTOCEREBELLAR HYPOPLASIA

RARS2, TSEN2, TSEN34, TSEN54, EXOSC3, AMPD2, CHMP1A, SEPSECS, CLP1, VPS53, CASK, PCLO AND VRK1 GENE ANALYSIS

Pontocerebellar hypoplasia (PCH) is a clinically and genetically heterogeneous group of neurodevelopmental disorders. PCH is characterized by prenatal onset of underdeveloped cerebral structures, in particular the cerebellum and the pons. PCH has been classified into a number of subtypes based on the clinical presentation and the spectrum of pathologic changes (Rudnik-Schöneborn et al. 2014 Am J Med Genet C Semin Med Genet 166C(2):173-83). Most patients present with global developmental delay, movement problems, intellectual disability and specific neurological symptoms related to the subtype.

Autosomal recessive variants in the RARS2, TSEN2, TSEN34, TSEN54EXOSC3AMPD2CHMP1A, SEPSECS, CLP1, VPS53 and VRK1 genes are known to cause subtypes of PCH (Schaffer et al. 2014 Cell 157(3):651-63; Akizu et al. 2013 Cell 154(3):505-517). In addition, X-linked dominant variants in the CASK gene cause Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia (Najm et al. 2008 Nat Genet 40(9):1065-7).

The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.