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Pontocerebellar hypoplasia type 1


Other Names for this Disease
  • Pontocerebellar hypoplasia with anterior horn cell disease
  • Pontocerebellar hypoplasia with infantile spinal muscular atrophy
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Overview



What is pontocerebellar hypoplasia type 1?

What are the symptoms of pontocerebellar hypoplasia type 1?

What causes pontocerebellar hypoplasia type 1?

How is pontocerebellar hypoplasia type 1 inherited?

How might pontocerebellar hypoplasia type 1 be treated?


What is pontocerebellar hypoplasia type 1?

Pontocerebellar hypoplasia type 1 (PCH1) is a genetic condition that affects the development of the brain. Individuals with this condition have an unusually small and underdeveloped cerebellum, which is the part of the brain that coordinates movement. A region of the brain called the pons also fails to develop properly. The pons, which is located at the base of the brain in an area called the brainstem, transmits signals from the cerebellum to the rest of the brain.[1] Individuals with PCH1 also experience a degeneration of the anterior horn cells. Because of the anterior horn cell involvement, this condition bears a resemblance to infantile spinal muscular atrophy, with severe muscle weakness.[1][2] Other signs and symptoms of PCH1 include very weak muscle tone (hypotonia), joint deformities called contractures, a small head size (microcephaly), and breathing problems that are present at birth. Mutations in the VRK1 gene have been identified in at least one family with PCH1.[1] The condition is inherited in an autosomal recessive manner.[1][2] Most children with PCH1 live only into infancy.[1]
Last updated: 4/16/2010

What are the symptoms of pontocerebellar hypoplasia type 1?

Pontocerebellar hypoplasia type 1 (PCH1) may first present in the prenatal period with reduced fetal movement. Polyhydramnios may also be noted. In most cases, the condition is obvious in the newborn period when respiratory insufficiency and muscle weakness present. Multiple contractures may also be present at birth, along with other motor impairment. Mental retardation and other signs of cerebellar disruption, including visual impairment, nystagmus and ataxia, may follow the initial presentation.[2]
Last updated: 4/16/2010

What causes pontocerebellar hypoplasia type 1?

A specific mutations in the VRK1 gene has caused PCH1 in at least one family.[1] Specific mutations in RARS2 and TSEN54 have also been associated with PCH1. TSEN54 mutations were identified in one case from a family with three siblings with PCH1; DNA was only available in one of the three siblings. Mutations in RARS2 were also identified in one case with PCH1.[3]

In general, there is no known genetic cause for the majority of PCH1 cases and no other genes have been linked to PCH1 yet, with the exception of rare cases associated with TSEN54, RARS2 and VRK1 mutations. In fact, only fifteen families with PCH1 have been published thus far; of these, mutations were only identified in 3 families. Further research on these and other candidate genes in PCH1 is necessary to identify mutations involved in the remaining majority of the PCH1 cases.[3]

Specific mutations in other genes have been shown to cause the various other forms of pontocerebellar hypoplasia and include the RARS2, TSEN2, TSEN34, and TSEN54 genes. Mutations in three related genes, TSEN2, TSEN34, and TSEN54, can result in PCH2.[1] TSEN54 gene mutations can also cause PCH4 and PCH5.[2951] Mutations in the RARS2 gene can cause PCH6. The genetic cause of PCH3 is unknown.[1]
Last updated: 7/20/2011

How is pontocerebellar hypoplasia type 1 inherited?

Pontocerebellar hypoplasia type 1 (PCH1) is inherited in an autosomal recessive pattern, which means both copies of the associated gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. This means that parents who are carriers of this condition have a 25% chance of having an affected child.[1] 
Last updated: 7/20/2011

How might pontocerebellar hypoplasia type 1 be treated?

There is no standard therapy for pontocerebellar hypoplasia type 1. Treatment is symptomatic and supportive.
Last updated: 4/16/2010

References
  1. Pontocerebellar hypoplasia. Genetics Home Reference (GHR). December 2009; http://ghr.nlm.nih.gov/condition=pontocerebellarhypoplasia. Accessed 7/20/2011.
  2. Omar S, Ajibola A. Pontocerebellar Hypoplasia. National Organization for Rare Disorders (NORD). 2009; http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Pontocerebellar%20Hypoplasia. Accessed 4/16/2010.
  3. Namavar Y et al.. Orphanet Journal of Rare Diseases. 2011; 6(50):http://www.ojrd.com/content/6/1/50. Accessed 7/20/2011.