Pontocerebellar hypoplasia
Pontocerebellar hypoplasias (PCH) are a group of rare hereditary, neurodegenerative disorders in which symptoms appear in the perinatal stage. They are classified into different subtypes and their incidence is unknown. Here we analyze pathogenic variants in the TSEN54 gene that have been associated with subtypes 2,4 and 5.
Symptoms
Clinical features of pontocerebellar hypoplasias include severe developmental delay, microcephaly (reduced head size) and involuntary movements. Epilepsy is present in approximately 50% of cases. Pontocerebellar hypoplasia type 2 is the most common subtype, with the first symptoms appearing in the neonatal stage and causing severe voluntary motor developmental delay and progressive posterior microcephaly.
Disease management
Treatment for all types of pontocerebellar hypoplasia is only symptomatic and the prognosis is not favorable, as most patients die during infancy or childhood.
Genes analyzed
Bibliography
Budde BS, Namavar Y, Barth PG, et al . tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. Nat Genet. 2008 Sep;40(9):1113-8.
Namavar Y, Chitayat D, Barth PG, van Ruissen F, de Wissel MB, Poll-The BT, Silver R, Baas F . TSEN54 mutations cause pontocerebellar hypoplasia type 5. Eur J Hum Genet. 2011 Jun;19(6):724-6.
Sánchez-Albisua I, Frölich S, Barth PG, Steinlin M, Krägeloh-Mann I.Natural course of pontocerebellar hypoplasia type 2A. Orphanet J Rare Dis. 2014 May 5;9:70. doi: 10.1186/1750-1172-9-70.
van Dijk T, Baas F. TSEN54 Pontocerebellar Hypoplasia. 2009 Sep 8 [updated 2020 May 28]. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023.
