Arginyl-Trna Synthetase; Cerebellar Atrophy with Progressive Microcephaly; CLAM; Encephalopathy, Fatal Infantile, With Olivopontocerebellar Hyperplasia; Fetal-Onset Olivopontocerebellar Hypoplasia; Olivopontocerebellar Hypoplasia, Fetal-Onset; PCH With Optic Atrophy; Pontocerebellar Hypoplasia with Anterior Horn Cell Disease; Pontocerebellar Hypoplasia With Infantile Spinal Muscular Atrophy; Pontocerebellar Hypoplasia with Progressive Cerebral Atrophy; RARS; Volendam Neurodegenerative Disease; Congenital Pontocerebellar Hypoplasia

Pontocerebellar Hypoplasia (PCH) is a group of related conditions that affect the development of the brain. The term "pontocerebellar" refers to the pons and the cerebellum, which are the brain structures that are most severely affected in many forms of this disorder. The pons is located at the base of the brain in an area called the brainstem, where it transmits signals between the cerebellum and the rest of the brain. The cerebellum, which is located at the back of the brain, normally coordinates movement. The term "hypoplasia" refers to the underdevelopment of these brain regions.

PCH 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.

PCH can result from mutations in several genes. About half of all cases of PCH1 are caused by mutations in the EXOSC3 gene. PCH1 can also result from mutations in several other genes, including TSEN54, RARS2, and VRK1. PCH2 is caused by mutations in the TSEN54, TSEN2, TSEN34, or SEPSECS gene. caused by mutations in other genes. In some cases, the genetic cause of PCH is unknown.

Diagnostic testing: The diagnosis of PCH is made by:

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  A history and physical exam;

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  Genetic testing (only available for certain types);

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  Magnetic resonance imaging (MRI) of the brain and spinal cord;

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  Computed tomography (CT) scan of the brain;

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  Serial ultrasound scans;

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  Nerve conduction studies;

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  Electroencephalograph (EEG) scan; and

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  Muscle, skin, and nerve biopsy (in types with known genetic mutations.

Physical findings: Signs and symptoms for PCH vary depending on the type. The signs and symptoms that are consistent for all types of PCH are:

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  Abnormally small cerebellum and brain stem;

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  Psychomotor retardation;

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  Problems with movement; and

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  Severe to profound intellectual disability.

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  Other signs and symptoms of PCH may include:

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  Microcephaly;

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  Encephalopathy;

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  Joint contractures;

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  Severe muscle weakness;

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  Nystagmus (uncontrolled eye movements);

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  Ataxia (lack of muscle control or coordination of voluntary movements);

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  Dystonia (involuntary repetitive or twisting movements;

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  Seizures;

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  Hypotonia (poor muscle tone);

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  Hypertonia (too much muscle tone); and

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  Visual impairment.

ICD-9: 742.2

ICD-10: Q04.3

Researchers have described at least ten types of pontocerebellar hypoplasia. 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 prevalence of pontocerebellar hypoplasia is unknown, although most forms of the disorder appear to be very rare.

There is no known cure for PCH. Treatment of PCH is symptomatic and supportive.

Suggested MER for Evaluation:

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  Clinical history and examination that describes the diagnostic features of the impairment;

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  Genetic testing (only available for certain types);

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  MRI of the brain and spinal cord;

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  CT scan of the brain;

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  Serial ultrasound scans;

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  Nerve conduction studies;

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  EEG; or

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  Muscle, skin, and nerve biopsy (in types with known genetic mutations).

Suggested Listings for Evaluation:

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