OMIM ID:
Pontocerebellar Hypoplasia 3
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Optic atrophy is an inconsistent feature (sometimes even unilateral) of patients with PCH. Cortical blindness has also been described. There may be dysmorphic facial features such as wide palpebral fissures, epicanthal folds, and prominent eyes.
Systemic Features
Infants are generally small and hypotonic at birth. The skull is small and often brachycephalic. The ears are large and low-set and facial dysmorphism (full cheeks, long philtrum) is present. Infants have poor head control and truncal ataxia. Later, hyperreflexia and spasticity become evident. Seizures are common. Developmental delays, both somatic and mental, are nearly universal and large joint contractures are often seen. Many of these signs are progressive.
Brain imaging generally reveals cerebral and cerebellar atrophy, a hypoplastic corpus callosum, a small cerebellar vermis, and a hypoplastic brainstem. Short stature is a feature and early death often occurs.
Genetics
Inheritance
PCH3 is one of at least 10 syndromes belonging to a clinically and genetically heterogeneous group of conditions known as pontocerebellar hypoplasias. Members of this group, while individually rare, nevertheless collectively account for a significant proportion of what was once labeled cerebral palsy.
PCH3 results from homozygous mutations in the PCLO gene (7q21).
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.