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TSEN54-Related Pontocerebellar Hypoplasia.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2009 Sep 8 [updated 2016 Jul 14].

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:

TSEN54-related pontocerebellar hypoplasia (PCH) includes three PCH types (PCH2, 4, and 5) that share characteristic neuroradiologic and neurologic findings. The three types (which differ mainly in life expectancy) were thought to be distinct entities before their molecular basis was known. Children with PCH2 usually succumb before age ten years, whereas those with PCH4 and 5 usually succumb as neonates. Children with PCH2 have generalized clonus, incoordination of sucking and swallowing, impaired motor and cognitive development with lack of voluntary motor development, central visual impairment, and an increased risk for rhabdomyolysis complicating severe infections. Epilepsy is present in approximately 50%. Neonates with PCH4 often have seizures, multiple joint contractures ("arthrogryposis"), generalized clonus, and central respiratory impairment. PCH5, which resembles PCH4, has been described in one family.

DIAGNOSIS/TESTING:

The diagnosis of TSEN54-related PCH is suspected in children with characteristic neuroradiologic and neurologic findings, and confirmed by the presence of biallelic TSEN54 pathogenic variants.

MANAGEMENT:

Treatment of manifestations: PCH2: Treatment of irritability, swallowing incoordination, epilepsy, and central visual impairment is symptomatic. Physiotherapy can be helpful. PCH4 and 5: No specific therapy is available. Prevention of secondary complications: PCH2: Assuring adequate hydration during prolonged periods of high fever may help avoid rhabdomyolysis. Surveillance: PCH2: Monitoring of respiratory function may be necessary to detect sleep apnea.

GENETIC COUNSELING:

TSEN54-related PCH is inherited in an autosomal recessive manner. At conception, 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. Individuals with TSEN54-related PCH are not known to have reproduced. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family are known.

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