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EXOSC3-Related Pontocerebellar Hypoplasia.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2014 Aug 21.

Author information

1
Academic Medical Center, Department of Neurogenetics, University of Amsterdam, Amsterdam, The Netherlands
2
Emma Children’s Hospital, Pediatric Neurology, University of Amsterdam, Amsterdam, The Netherlands

Excerpt

CLINICAL CHARACTERISTICS:

EXOSC3-related pontocerebellar hypoplasia (PCH) is characterized by abnormalities in the posterior fossa and degeneration of the anterior horn cells. At birth, skeletal muscle weakness manifests as hypotonia (sometimes with congenital joint contractures) and poor feeding. In persons with prolonged survival, spasticity, dystonia, and seizures become evident. Within the first year of life respiratory insufficiency and swallowing difficulties are common. Intellectual disability is severe. Life expectancy ranges from a few weeks to adolescence. To date, 51 individuals with PCH from 36 families with mutation of EXOSC3 have been described.

DIAGNOSIS/TESTING:

The diagnosis is suspected in infants and children with characteristic clinical findings (including evidence of anterior horn cell disease) and characteristic neuroradiologic findings (hypoplasia and/or atrophy of the cerebellum and pons in varying degrees; equal involvement of the cerebellar vermis and cerebellar hemispheres). The diagnosis is established by identification of biallelic EXOSC3 pathogenic variants on molecular genetic testing.

MANAGEMENT:

Treatment of manifestations: No specific therapy is available. Treatment is symptomatic. Contractures and scoliosis are managed by passive or active movement and bracing as needed. Aspiration risk and seizures are managed in a routine manner. Education is adapted to the level of cognitive handicap. Surveillance: Regular examinations to address: growth and nutritional status (including problems with feeding and risk of aspiration); respiratory function; joint contractures and scoliosis. Observation for and management of epileptic seizures.

GENETIC COUNSELING:

EXOSC3-related PCH is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. If the EXOSC3 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible.

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