Pontocerebellar hypoplasia

From Wikipedia, the free encyclopedia
Jump to: navigation, search

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurodegenerative disorders caused by genetic mutations and characterised by impaired development of various parts of the brain (cerebellum, brainstem).

Where known, these disorders are inherited in an autosomal recessive fashion. As with the majority of genetic disorders,[citation needed] there is no known cure to PCH.

For the Pontocerebellar hypoplasia caused by a CASK gene defect the above is incorrect. A number of CASK gene defects are de novo mutations.

The following values seem to be aberrant in children with CASK gene defects: lactate, pyruvate, 2 ketoglutarate, adipic acid, suberic acid which seems to backup the thesis of Konark Mukherjee that CASK affects mitochondrial function. (see publication below) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075472/ MCT oil is being provided to a number of children de dato 25/08/2014, the effects on their blood values is not yet known. It however seems wise that the children are seen by a doctor specialized in mitochondrial disfunction.

Also there is an assumption that Phosphoinositide_3-kinase in the Inositol metabolism is impacted in the CASK related disfunction. http://en.wikipedia.org/wiki/Phosphoinositide_3-kinase# , causing folic acid metabolization problems. This thesis will have to be studied further.


Pontocerebellar hypoplasia is classified as follows:

Type OMIM Gene Locus Distinctive features Alternate names
1A (PCH1A) 607596 VRK1 14q32 Anterior horn cell degeneration Spinal muscular atrophy with pontocerebellar hypoplasia (SMA-PCH)
1B (PCH1B) 614678 EXOSC3 9p13.2 Hypotonia, respiratory insufficiency, muscle atrophy
2A (PCH2A) 277470 TSEN54 17q25.1 Dyskinetic movements, seizures (frequently) Volendam neurodegenerative disease
2B (PCH2B) 612389 TSEN2 3p25.2
2C (PCH2C) 612390 TSEN34 19q13.42
2D (PCH2D) 613811 SEPSECS 4p15.2 Progressive cerebello-cerebral atrophy (PCCA)
3 (PCH3) 608027 CLAM 7q11–q21 Seizures, short stature, optic atrophy CLAM-PCH, cerebellar atrophy with progressive microcephaly
4 (PCH4) 225753 TSEN54 17q25.1 Severe prenatal form of PCH2 with polyhydramnios, contractures, myoclonus, apneic episodes and early death following birth
5 (PCH5) 610204 unknown unknown Severe prenatal form, described in one family Olivopontocerebellar hypoplasia (OPCH)
6 (PCH6) 611523 RARS2 6q15 Severe encephalopathy in the newborn with hypotonia, and inconstantly: intractable seizures, edema, increased lactate blood levels, mitochondrial respiratory chain defects
7 (PCH7)[1][2] unknown unknown Hypotonia, apneic episodes, seizures, vanishing testis

It should be noted that pontine and cerebellar hypoplasia is also observed in certain phenotypes of X-linked mental retardation (so called MICPCH, OMIM: 300749).


  1. Facial features (dysmorphism) of patients with one form of pontocerebellar hypoplasia due to mutations in the CASK gene. A and B: patient at 1 year (A) and 4 years (B). C: patient, 18 months. D: patient, 13 years. E: patient, 13 years. F: patient, 12 years. Note minor facial dysmorphism: round face, small chin, well-drawn eyebrows in the younger patients; longer face, high and large nasal bridge, long nose, protuding maxilla, in the older patients.
  2. Magnetic resonance imaging (MRI) examples of patients with pontocerebellar hypoplasia with CASK mutations. A. Sagittal images showing different degrees of hypoplasia (incomplete formation) of the pons and vermis (parts of the brain). Numbers represent different patients. Figure 9a shows an MRI of a patient at age 4 months and figure 9b shows the same patient at age 11 years. There is no progression of the lesions between successive MRI in patient 9. Note that in all patients, the pons is very small but has a relative sparing of its buldging, mainly in its superior part. Hypoplasia predominates at the lower part of the pons. Vermis hypoplasia is very variable, severe in patient 13, very slight in patient 10-11-12 and also predominates at the inferior part. B. Coronal images showing varying degrees of cerebellar hemispheric (one of two halves of a part of the brain) hypoplasia. Hemispheres are frequently asymmetric. Note that the vermis does not protrude from the hemispheres indicating similar involvement of the vermis and the hemispheres. This pattern is different from that of PCH2 in which the vermis is relatively spared leading to the classic image of a "dragonfly", the protruding vermis being the body of the dragonfly and the hemispheres, the wings.

See also[edit]


  1. ^ Anderson, C.; Davies, J. H.; Lamont, L.; Foulds, N. (2011). "Early pontocerebellar hypoplasia with vanishing testes: A new syndrome?". American Journal of Medical Genetics Part A 155 (4): 667. doi:10.1002/ajmg.a.33897.  edit
  2. ^ Namavar, Y.; Barth, P. G.; Poll-The, B.; Baas, F. (2011). "Classification, diagnosis and potential mechanisms in Pontocerebellar Hypoplasia". Orphanet Journal of Rare Diseases 6: 50. doi:10.1186/1750-1172-6-50. PMC 3159098. PMID 21749694.  edit

Further reading[edit]