Search for a rare disease
Other search option(s)
Pontocerebellar hypoplasia type 4
Pontocerebellar hypoplasia type 4 (PCH4) is a very rare form of PCH (see this term), characterized by prenatal onset of polyhydramnios and contractures followed by hypertonia, severe clonus, primary hypoventilation leading to an early postnatal death.
PCH4 has been reported in 10 families to date.
PCH4 is characterized prenatally by polyhydramnios. Neonates present with microcephaly, central apnea requiring respiratory support, dysmorphism (sloping forehead, midface hypoplasia, micrognathia), contractures (50%) ''arthrogryposis'', severe clonus,and hypertonia. PCH4 affected babies usually do not live beyond the neonatal period. Weaning from mechanical ventilation is difficult and usually fails.
PCH4 is caused by a compound heterozygosity for p.A307S plus non-sense or splice site mutations in the TSEN54 gene. There is significant overlap both in phenotype and in genotype between pontocerebellar hypoplasia types 4 and 5 (see this term). PCH4 is inherited in an autosomal recessive manner.
MRI (usually performed at autopsy) demonstrates microcephaly due to delayed neocortical maturation with underdeveloped cerebral hemispheres, increased volume of extracerebral cerebrospinal fluid, wide midline cava, pontocerebellar hypoplasia with large denuded areas without folia of the cerebellar hemispheric cortex and a severely affected vermis.