Pontocerebellar hypoplasia

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Pontocerebellar hypoplasia
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Microcephaly, developmental delay, intellectual disability, seizures, muscle weakness
Complications	N/A
Onset	Infancy
Duration	Lifelong
Types	N/A
Causes	Genetic mutation
Risks	Family history of the condition
Diagnosis	Genetic testing, MRI
Differential diagnosis	Cerebellar hypoplasia, spinocerebellar ataxia
Prevention	N/A
Treatment	Supportive care, physical therapy, occupational therapy
Medication	N/A
Prognosis	Variable, often poor
Frequency	Rare
Deaths	N/A

Definition

Pontocerebellar hypoplasia (PCH) is a group of conditions affecting the brain characterized by underdevelopment of the cerebellum and pons. The cerebellum normally coordinates movement and the pons (located in the brainstem) transmits signals from the cerebellum to the rest of the brain.

Forms

Several forms of PCH have been described, each having some different signs and symptoms but all characterized by problems with movement, delayed psychomotor development, and intellectual disability. Each form has a different genetic cause.

Cause

• The different forms of pontocerebellar hypoplasia (PCH) are generally caused by mutations in several different genes.
• These genes appear to play important roles in the development and survival of nerve cells.
• However, it is unclear how mutations in these genes disrupt the normal development of the cerebellum and pons.
• PCH1A can be caused by mutations in the VRK1 gene
• PCH1B is caused my mutations in the EXOSC3 gene
• PCH2 is caused by mutations in the TSEN54, TSEN2, TSEN34, and SEPSECS genes
• PCH4 is caused by mutations in the TSEN54 gene
• PCH6 is caused by mutations in the RARS2 gene
• PCH8 is caused by mutations in the CHMP1A gene
• Specific genes that cause PCH3, PCH5 and PCH7 have not yet been identified.
• Although experts agree that PCH has a genetic cause, other causes (such as infectious or toxic) have been reported or suspected in some cases.

Inheritance

Although each form has a different genetic cause, they are all inherited in an autosomal recessive manner.

Signs and symptoms

• Pontocerebellar hypoplasia also causes impaired growth of other parts of the brain, leading to an unusually small head size (microcephaly).
• This microcephaly is usually not apparent at birth but becomes noticeable as brain growth continues to be slow in infancy and early childhood.
• All forms of this condition are characterized by impaired brain development, delayed development overall, problems with movement, and intellectual disability.
• The brain abnormalities are usually present at birth, and in some cases they can be detected before birth.
• Many children with pontocerebellar hypoplasia live only into infancy or childhood, although some affected individuals have lived into adulthood.
• The two major forms of pontocerebellar hypoplasia are designated as type 1 (PCH1) and type 2 (PCH2).
• In addition to the brain abnormalities described above, PCH1 causes problems with muscle movement resulting from a loss of specialized nerve cells called motor neurons in the spinal cord, similar to another genetic disorder known as spinal muscular atrophy.
• Individuals with PCH1 also have very weak muscle tone (hypotonia), joint deformities called contractures, vision impairment, and breathing and feeding problems that are evident from early infancy.
• Common features of PCH2 include a lack of voluntary motor skills (such as grasping objects, sitting, or walking), problems with swallowing (dysphagia), and an absence of communication, including speech.
• Affected children typically develop temporary jitteriness (generalized clonus) in early infancy, abnormal patterns of movement described as chorea or dystonia, and stiffness (spasticity).
• Many also have impaired vision and seizures.
• The other forms of pontocerebellar hypoplasia, designated as type 3 (PCH3) through type 10 (PCH10), appear to be rare and have each been reported in only a small number of individuals.

Diagnosis

Molecular Genetics Tests include:

• Deletion/duplication analysis
• Mutation scanning of select exons
• Sequence analysis of the entire coding region

NIH genetic and rare disease info

• NIH info on Pontocerebellar hypoplasia

Pontocerebellar hypoplasia is a rare disease.

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