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Pontocerebellar hypoplasia type 2(PCH2)

MedGen UID:
420956
•Concept ID:
C2932714
•
Congenital Abnormality; Disease or Syndrome
Synonyms: PCH2; Progressive microcephaly from birth extrapyramidal dyskinesia chorea epilepsy
SNOMED CT: Congenital pontocerebellar hypoplasia type 2 (715463008); PCH2 - pontocerebellar hypoplasia type 2 (715463008); Pontocerebellar hypoplasia type 2 (715463008)
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: TSEN54, TSEN15, TSEN2, TSEN34, VPS53, SEPSECS
 
Monarch Initiative: MONDO:0016759
Orphanet: ORPHA2524

Disease characteristics

Excerpted from the GeneReview: TSEN54 Pontocerebellar Hypoplasia
TSEN54 pontocerebellar hypoplasia (TSEN54-PCH) comprises three PCH phenotypes (PCH2, 4, and 5) that share characteristic neuroradiologic and neurologic findings. The three PCH phenotypes (which differ mainly in life expectancy) were considered to be distinct entities before their molecular basis was known. PCH2. Children usually succumb before age ten years (those with PCH4 and 5 usually succumb as neonates). Children with PCH2 have generalized clonus, uncoordinated sucking and swallowing, impaired cognitive development, lack of voluntary motor development, cortical blindness, and an increased risk for rhabdomyolysis during severe infections. Epilepsy is present in approximately 50%. PCH4. Neonates often have seizures, multiple joint contractures ("arthrogryposis"), generalized clonus, and central respiratory impairment. PCH5 resembles PCH4 and has been described in one family. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  GeneReview Scope  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Tessa van Dijk  |  Frank Baas   view full author information

Additional description

From OMIM
Pontocerebellar hypoplasia (PCH) represents a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem. PCH type 2 (PCH2) is characterized by progressive microcephaly from birth combined with extrapyramidal dyskinesia and chorea, epilepsy, and normal spinal cord findings (Barth, 1993). For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596). Genetic Heterogeneity of Pontocerebellar Hypoplasia Type 2 PCH2B (612389) is caused by mutation in the TSEN2 gene (608753) on chromosome 3p25, and PCH2C (612390) is caused by mutation in the TSEN34 gene (608754) on chromosome 19q13. PCH2D (613811) is caused by mutation in the SEPSECS gene (613009) on chromosome 4p15. PCH2E (615851) is caused by mutation in the VPS53 gene (615850) on chromosome 17p13. PCH2F (617026) is caused by mutation in the TSEN15 gene (608756) on chromosome 1q25. The TSEN2 and TSEN34 genes encode catalytic subunits of the tRNA splicing endonuclease, whereas the TSEN54 gene encodes a noncatalytic subunit. The SEPSECS gene is also involved in tRNA processing.  http://www.omim.org/entry/277470

Professional guidelines

PubMed

Targeted carrier screening for four recessive disorders: high detection rate within a founder population.
Mathijssen IB, Henneman L, van Eeten-Nijman JM, Lakeman P, Ottenheim CP, Redeker EJ, Ottenhof W, Meijers-Heijboer H, van Maarle MC
Eur J Med Genet 2015 Mar;58(3):123-8. Epub 2015 Jan 30 doi: 10.1016/j.ejmg.2015.01.004. PMID: 25641760

Recent clinical studies

Etiology

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
Natural course of pontocerebellar hypoplasia type 2A.
Sánchez-Albisua I, Frölich S, Barth PG, Steinlin M, Krägeloh-Mann I
Orphanet J Rare Dis 2014 May 5;9:70. doi: 10.1186/1750-1172-9-70. PMID: 24886362Free PMC Article
Novel mutations in TSEN54 in pontocerebellar hypoplasia type 2.
Battini R, D'Arrigo S, Cassandrini D, Guzzetta A, Fiorillo C, Pantaleoni C, Romano A, Alfei E, Cioni G, Santorelli FM
J Child Neurol 2014 Apr;29(4):520-5. Epub 2013 Jan 9 doi: 10.1177/0883073812470002. PMID: 23307886
Pontocerebellar hypoplasia type 2 and TSEN2: review of the literature and two novel mutations.
Bierhals T, Korenke GC, Uyanik G, Kutsche K
Eur J Med Genet 2013 Jun;56(6):325-30. Epub 2013 Apr 3 doi: 10.1016/j.ejmg.2013.03.009. PMID: 23562994
Pontocerebellar hypoplasia type 2: variability in clinical and imaging findings.
Steinlin M, Klein A, Haas-Lude K, Zafeiriou D, Strozzi S, Müller T, Gubser-Mercati D, Schmitt Mechelke T, Krägeloh-Mann I, Boltshauser E
Eur J Paediatr Neurol 2007 May;11(3):146-52. Epub 2007 Feb 22 doi: 10.1016/j.ejpn.2006.11.012. PMID: 17320436

Diagnosis

Spasmodic Abdominal Pain and Other Gastrointestinal Symptoms in Pontocerebellar Hypoplasia Type 2.
Janzarik WG, Krägeloh-Mann I, Langer T, van Buiren M, Schaefer HE, Gerner P
Neuropediatrics 2021 Dec;52(6):495-498. Epub 2021 Jul 12 doi: 10.1055/s-0041-1730445. PMID: 34255333
Natural course of pontocerebellar hypoplasia type 2A.
Sánchez-Albisua I, Frölich S, Barth PG, Steinlin M, Krägeloh-Mann I
Orphanet J Rare Dis 2014 May 5;9:70. doi: 10.1186/1750-1172-9-70. PMID: 24886362Free PMC Article
Pontocerebellar hypoplasia type 2 and TSEN2: review of the literature and two novel mutations.
Bierhals T, Korenke GC, Uyanik G, Kutsche K
Eur J Med Genet 2013 Jun;56(6):325-30. Epub 2013 Apr 3 doi: 10.1016/j.ejmg.2013.03.009. PMID: 23562994
Molecular and neuroimaging findings in pontocerebellar hypoplasia type 2 (PCH2): is prenatal diagnosis possible?
Graham JM Jr, Spencer AH, Grinberg I, Niesen CE, Platt LD, Maya M, Namavar Y, Baas F, Dobyns WB
Am J Med Genet A 2010 Sep;152A(9):2268-76. doi: 10.1002/ajmg.a.33579. PMID: 20803644Free PMC Article
Pontocerebellar hypoplasia type 2: a neuropathological update.
Barth PG, Aronica E, de Vries L, Nikkels PG, Scheper W, Hoozemans JJ, Poll-The BT, Troost D
Acta Neuropathol 2007 Oct;114(4):373-86. Epub 2007 Jul 20 doi: 10.1007/s00401-007-0263-0. PMID: 17641900Free PMC Article

Therapy

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

The impact of severe rare chronic neurological disease in childhood on the quality of life of families-a study on MLD and PCH2.
Ammann-Schnell L, Groeschel S, Kehrer C, Frölich S, Krägeloh-Mann I
Orphanet J Rare Dis 2021 May 10;16(1):211. doi: 10.1186/s13023-021-01828-y. PMID: 33971942Free PMC Article
Natural course of pontocerebellar hypoplasia type 2A.
Sánchez-Albisua I, Frölich S, Barth PG, Steinlin M, Krägeloh-Mann I
Orphanet J Rare Dis 2014 May 5;9:70. doi: 10.1186/1750-1172-9-70. PMID: 24886362Free PMC Article
Recurrent episodes of rhabdomyolysis in pontocerebellar hypoplasia type 2.
Zafeiriou DI, Ververi A, Tsitlakidou A, Anastasiou A, Vargiami E
Neuromuscul Disord 2013 Feb;23(2):116-9. Epub 2012 Nov 22 doi: 10.1016/j.nmd.2012.08.004. PMID: 23177318
Near-total absence of the cerebellum.
Gardner RJ, Coleman LT, Mitchell LA, Smith LJ, Harvey AS, Scheffer IE, Storey E, Nowotny MJ, Sloane RA, Lubitz L
Neuropediatrics 2001 Apr;32(2):62-8. doi: 10.1055/s-2001-13882. PMID: 11414645
Fatal outcome in a case of pontocerebellar hypoplasia type 2.
Grellner W, Rohde K, Wilske J
Forensic Sci Int 2000 Sep 11;113(1-3):165-72. doi: 10.1016/s0379-0738(00)00270-x. PMID: 10978619

Clinical prediction guides

The impact of severe rare chronic neurological disease in childhood on the quality of life of families-a study on MLD and PCH2.
Ammann-Schnell L, Groeschel S, Kehrer C, Frölich S, Krägeloh-Mann I
Orphanet J Rare Dis 2021 May 10;16(1):211. doi: 10.1186/s13023-021-01828-y. PMID: 33971942Free PMC Article
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 2: further clinical characterization and evidence of positive response of dyskinesia to levodopa.
Grosso S, Mostadini R, Cioni M, Galluzzi P, Morgese G, Balestri P
J Neurol 2002 May;249(5):596-600. doi: 10.1007/s004150200069. PMID: 12021950
Pontocerebellar hypoplasia type 2 and Reye-like syndrome.
Sans-Fitó A, Campistol-Plana J, Mas-Salguero MJ, Póo-Argüelles P, Fernández-Alvarez E
J Child Neurol 2002 Feb;17(2):132-4. doi: 10.1177/088307380201700208. PMID: 11952074
Fatal outcome in a case of pontocerebellar hypoplasia type 2.
Grellner W, Rohde K, Wilske J
Forensic Sci Int 2000 Sep 11;113(1-3):165-72. doi: 10.1016/s0379-0738(00)00270-x. PMID: 10978619

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