Pontocerebellar hypoplasia type 6

Alternate names

Encephalopathy fatal infantile with mitochondrial respiratory chain defects

Summary

Pontocerebellar hypoplasia type 6 (PCH6) is a rare form of pontocerebellar hypoplasia characterized clinically at birth by hypotonia, clonus, epilepsy impaired swallowing and from infancy by progressive microencephaly, spasticity and lactic acidosis.

Epidemiology

PCH6 is reported in less than 10 cases to date

Cause

PCH6 is caused by missense and splice site mutations in the mitochondrial arginyl-transfer RNA synthetase (RARS2) gene located to 6q16.1.

Signs and symptoms

PCH6 is characterized clinically at birth by generalized hypotonia, lethargy and dysphagia. The clinical profile is characterized from infancy by a profound developmental delay, progressive microencephaly, hypotonia or spasticity treatment-resistant epilepsy.

Diagnosis

MRI demonstrates neocortical and more severe cerebral cortical atrophy (more severe than in other types of PCH), pontocerebellar hypoplasia with pons and cerebellum are equally affected. RARS2 mutation positive PCH6 patients can be screened by analysis of increased lactate in blood and cerebrospinal fluid. Biochemical analysis in muscle may demonstrate reduced activity of mitochondrial complexes I, III, and IV and normal activity of mitochondrial complex II.

Prognosis

Prognosis is poor, exact life expectancy is unknown but in most cases does not exceed infancy.

NIH genetic and rare disease info

• NIH info on Pontocerebellar hypoplasia type 6

Pontocerebellar hypoplasia type 6 is a rare disease.