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Congenital pontocerebellar hypoplasia type 1

MedGen UID:
1780208
•Concept ID:
C5442006
•
Disease or Syndrome
Synonym: Pontocerebellar hypoplasia type 1
SNOMED CT: Congenital pontocerebellar hypoplasia type 1 (718610008); PCH1 - pontocerebellar hypoplasia type 1 (718610008); Pontocerebellar hypoplasia type 1 (718610008); Norman disease (718610008)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Related genes: EXOSC3, EXOSC8, VRK1, EXOSC9
 
Monarch Initiative: MONDO:0016396
Orphanet: ORPHA2254

Definition

PCH1 often has prenatal characteristics of polyhydramnios with arthrogryposis multiplex congenita. Neonates with PCH1 present with hypotonia, impaired swallowing with consequent feeding difficulties and progressive microcephaly which mostly develops postnatally. Subsequently a severe psychomotor deficit becomes apparent. The clinical course is severe. About 40 patients with PCH1 have been reported. To date recessive mutations have been noted in the EXOSC3 gene and in single cases recessive mutations have been found in the tRNA splicing endonuclease homolog 54 (TSEN54), mitochondrial arginyl-transfer RNA synthetase (RARS2), and in the vaccinia-related kinase 1 (VRK1) gene. PCH1 has an autosomal recessive transmission. [from SNOMEDCT_US]

Professional guidelines

PubMed

Prenatal diagnosis of pontocerebellar hypoplasia with postnatal follow-up.
Jaillard A, Valence S, Vande Perre S, Dhombres F, Héron D, Billette de Villemeur T, Keren B, Afenjar A, Qebibo L, Harion M, Quenum-Miraillet G, Rodriguez D, Jouannic JM, Burglen L, Garel C
Prenat Diagn 2024 Jan;44(1):35-48. Epub 2024 Jan 2 doi: 10.1002/pd.6495. PMID: 38165124
Genetic and prenatal diagnosis of a Chinese pedigree with pathogenic TOE1 variants causing pontocerebellar hypoplasia type 7.
Guo H, Deng Z, Xu Q, Wang Z, Zeng X, Hong X, Wang Q, Sun Y, Yuan H
J Matern Fetal Neonatal Med 2023 Dec;36(2):2250895. doi: 10.1080/14767058.2023.2250895. PMID: 37635087
Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature.
Ivanov I, Atkinson D, Litvinenko I, Angelova L, Andonova S, Mumdjiev H, Pacheva I, Panova M, Yordanova R, Belovejdov V, Petrova A, Bosheva M, Shmilev T, Savov A, Jordanova A
Eur J Paediatr Neurol 2018 Jul;22(4):674-681. Epub 2018 Apr 3 doi: 10.1016/j.ejpn.2018.03.011. PMID: 29656927

Recent clinical studies

Etiology

Delineating the phenotype and genetic basis of AMPD2-related pontocerebellar hypoplasia.
Gilboa T, Elefant N, Meiner V, Hacohen N
Neurogenetics 2023 Jan;24(1):61-66. Epub 2022 Nov 29 doi: 10.1007/s10048-022-00706-4. PMID: 36445597
Clinical, radiological, and genetic variation in pontocerebellar hypoplasia disorder and our clinical experience.
Bilge S, Mert GG, Hergüner Ö, Özcanyüz D, Bozdoğan ST, Kaya Ö, Havalı C
Ital J Pediatr 2022 Sep 8;48(1):169. doi: 10.1186/s13052-022-01349-9. PMID: 36076253Free PMC Article
Pontocerebellar hypoplasia type 11: Does the genetic defect determine timing of cerebellar pathology?
Laugwitz L, Buchert R, Groeschel S, Riess A, Grimmel M, Beck-Wödl S, Sturm M, Gohla G, Döbler-Neumann M, Krägeloh-Mann I, Haack TB
Eur J Med Genet 2020 Jul;63(7):103938. Epub 2020 Apr 28 doi: 10.1016/j.ejmg.2020.103938. PMID: 32360255
Brain morphometry in Pontocerebellar Hypoplasia type 2.
Ekert K, Groeschel S, Sánchez-Albisua I, Frölich S, Dieckmann A, Engel C, Krägeloh-Mann I
Orphanet J Rare Dis 2016 Jul 19;11(1):100. doi: 10.1186/s13023-016-0481-4. PMID: 27430971Free PMC Article
Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia.
Namavar Y, Barth PG, Poll-The BT, Baas F
Orphanet J Rare Dis 2011 Jul 12;6:50. doi: 10.1186/1750-1172-6-50. PMID: 21749694Free PMC Article

Diagnosis

Prenatal diagnosis of pontocerebellar hypoplasia with postnatal follow-up.
Jaillard A, Valence S, Vande Perre S, Dhombres F, Héron D, Billette de Villemeur T, Keren B, Afenjar A, Qebibo L, Harion M, Quenum-Miraillet G, Rodriguez D, Jouannic JM, Burglen L, Garel C
Prenat Diagn 2024 Jan;44(1):35-48. Epub 2024 Jan 2 doi: 10.1002/pd.6495. PMID: 38165124
Clinical, radiological, and genetic variation in pontocerebellar hypoplasia disorder and our clinical experience.
Bilge S, Mert GG, Hergüner Ö, Özcanyüz D, Bozdoğan ST, Kaya Ö, Havalı C
Ital J Pediatr 2022 Sep 8;48(1):169. doi: 10.1186/s13052-022-01349-9. PMID: 36076253Free PMC Article
Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature.
Ivanov I, Atkinson D, Litvinenko I, Angelova L, Andonova S, Mumdjiev H, Pacheva I, Panova M, Yordanova R, Belovejdov V, Petrova A, Bosheva M, Shmilev T, Savov A, Jordanova A
Eur J Paediatr Neurol 2018 Jul;22(4):674-681. Epub 2018 Apr 3 doi: 10.1016/j.ejpn.2018.03.011. PMID: 29656927
Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia.
Namavar Y, Barth PG, Poll-The BT, Baas F
Orphanet J Rare Dis 2011 Jul 12;6:50. doi: 10.1186/1750-1172-6-50. PMID: 21749694Free PMC Article
Pontocerebellar hypoplasia type 1.
Szabó N, Szabó H, Hortobágyi T, Túri S, Sztriha L
Pediatr Neurol 2008 Oct;39(4):286-8. doi: 10.1016/j.pediatrneurol.2008.06.017. PMID: 18805371

Therapy

Epilepsy in inherited metabolic disorders: a pediatric series.
Vitiello G, De Clemente V, Della Casa R, Romano A, Rosa M, Pascarella A, Riccitelli M, Parenti G, Del Giudice E
Minerva Pediatr 2012 Oct;64(5):513-20. PMID: 22992533
Rhabdomyolysis in pontocerebellar hypoplasia type 2 (PCH-2).
Barth PG, Ryan MM, Webster RI, Aronica E, Kan A, Ramkema M, Jardine P, Poll-The BT
Neuromuscul Disord 2008 Jan;18(1):52-8. Epub 2007 Sep 6 doi: 10.1016/j.nmd.2007.08.001. PMID: 17825555

Prognosis

ATAD3A-related pontocerebellar hypoplasia: new patients and insights into phenotypic variability.
Skopkova M, Stufkova H, Rambani V, Stranecky V, Brennerova K, Kolnikova M, Pietrzykova M, Karhanek M, Noskova L, Tesarova M, Hansikova H, Gasperikova D
Orphanet J Rare Dis 2023 Apr 24;18(1):92. doi: 10.1186/s13023-023-02689-3. PMID: 37095554Free PMC Article
Delineating the phenotype and genetic basis of AMPD2-related pontocerebellar hypoplasia.
Gilboa T, Elefant N, Meiner V, Hacohen N
Neurogenetics 2023 Jan;24(1):61-66. Epub 2022 Nov 29 doi: 10.1007/s10048-022-00706-4. PMID: 36445597
Pontocerebellar hypoplasia type 11: Does the genetic defect determine timing of cerebellar pathology?
Laugwitz L, Buchert R, Groeschel S, Riess A, Grimmel M, Beck-Wödl S, Sturm M, Gohla G, Döbler-Neumann M, Krägeloh-Mann I, Haack TB
Eur J Med Genet 2020 Jul;63(7):103938. Epub 2020 Apr 28 doi: 10.1016/j.ejmg.2020.103938. PMID: 32360255
EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations.
Eggens VR, Barth PG, Niermeijer JM, Berg JN, Darin N, Dixit A, Fluss J, Foulds N, Fowler D, Hortobágyi T, Jacques T, King MD, Makrythanasis P, Máté A, Nicoll JA, O'Rourke D, Price S, Williams AN, Wilson L, Suri M, Sztriha L, Dijns-de Wissel MB, van Meegen MT, van Ruissen F, Aronica E, Troost D, Majoie CB, Marquering HA, Poll-Thé BT, Baas F
Orphanet J Rare Dis 2014 Feb 13;9:23. doi: 10.1186/1750-1172-9-23. PMID: 24524299Free PMC Article
Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia.
Namavar Y, Barth PG, Poll-The BT, Baas F
Orphanet J Rare Dis 2011 Jul 12;6:50. doi: 10.1186/1750-1172-6-50. PMID: 21749694Free PMC Article

Clinical prediction guides

ATAD3A-related pontocerebellar hypoplasia: new patients and insights into phenotypic variability.
Skopkova M, Stufkova H, Rambani V, Stranecky V, Brennerova K, Kolnikova M, Pietrzykova M, Karhanek M, Noskova L, Tesarova M, Hansikova H, Gasperikova D
Orphanet J Rare Dis 2023 Apr 24;18(1):92. doi: 10.1186/s13023-023-02689-3. PMID: 37095554Free PMC Article
Delineating the phenotype and genetic basis of AMPD2-related pontocerebellar hypoplasia.
Gilboa T, Elefant N, Meiner V, Hacohen N
Neurogenetics 2023 Jan;24(1):61-66. Epub 2022 Nov 29 doi: 10.1007/s10048-022-00706-4. PMID: 36445597
Pontocerebellar hypoplasia type 11: Does the genetic defect determine timing of cerebellar pathology?
Laugwitz L, Buchert R, Groeschel S, Riess A, Grimmel M, Beck-Wödl S, Sturm M, Gohla G, Döbler-Neumann M, Krägeloh-Mann I, Haack TB
Eur J Med Genet 2020 Jul;63(7):103938. Epub 2020 Apr 28 doi: 10.1016/j.ejmg.2020.103938. PMID: 32360255
Brain morphometry in Pontocerebellar Hypoplasia type 2.
Ekert K, Groeschel S, Sánchez-Albisua I, Frölich S, Dieckmann A, Engel C, Krägeloh-Mann I
Orphanet J Rare Dis 2016 Jul 19;11(1):100. doi: 10.1186/s13023-016-0481-4. PMID: 27430971Free PMC Article
Pontocerebellar hypoplasia type 1: clinical spectrum and relevance of EXOSC3 mutations.
Rudnik-Schöneborn S, Senderek J, Jen JC, Houge G, Seeman P, Puchmajerová A, Graul-Neumann L, Seidel U, Korinthenberg R, Kirschner J, Seeger J, Ryan MM, Muntoni F, Steinlin M, Sztriha L, Colomer J, Hübner C, Brockmann K, Van Maldergem L, Schiff M, Holzinger A, Barth P, Reardon W, Yourshaw M, Nelson SF, Eggermann T, Zerres K
Neurology 2013 Jan 29;80(5):438-46. Epub 2013 Jan 2 doi: 10.1212/WNL.0b013e31827f0f66. PMID: 23284067Free PMC Article

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