Pontocerebellar hypoplasia type 5

Alternate names

Olivopontocerebellar hypoplasia fetal-onset

Definition

Pontocerebellar hypoplasia type 5 (PCH5) is a very rare severe form of PCH with prenatal onset and characterized by fetal onset of clonus or seizures-like activity persisting in infancy and microencephaly leading to early postnatal death. There is significant overlap both in phenotype and in genotype between pontocerebellar hypoplasia types 4 and 5.

Epidemiology

PCH5 is reported in 3 siblings to date.

Cause

PCH5 is caused by a compound heterozygosity for p.A307S plus splice site mutation in the gene.

Inheritance

Autosomal recessive inheritance, a 25% chance

PCH5 transmission is autosomal recessive inheritance.

Signs and symptoms

PCH5, clinically resembling PCH4 , is characterized by fetal onset of clonus or seizure-like episodes, microcephaly, cerebellar hypoplasia persisting in infancy and microencephaly leading to early postnatal death.

Diagnosis

• Clinically similar to PCH4, PCH5 is demonstrated on autopsy.
• MRI demonstrates inferior olivary dysplasia, and pontocerebellar hypoplasia with the vermis much more degenerated than cerebellar hemispheres. Pathological findings show and increased degeneration with Purkinje and granule cells in the vermis.

Antenatal diagnosis Antenatal diagnosis is possible by ultrasonic assessment of cerebellar width at 16-18 weeks gestation.

Treatment

PCH4 and PCH5: No specific therapy is available.

NIH genetic and rare disease info

• NIH info on Pontocerebellar hypoplasia type 5

Pontocerebellar hypoplasia type 5 is a rare disease.