OMIM ID:
Pontocerebellar Hypoplasia 7
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The ocular phenotype has not been fully evaluated. Optic atrophy, nystagmus, and strabismus have been reported in addition to dysmorphic periocular features such as epicanthal folds, upslanting lid fissures, and a flattened nasal bridge. Infants frequently do not fix and follow.
Systemic Features
Infants may be small at birth and subsequent psychomotor development is delayed. The ears are large and the palate is highly arched. Hypotonia is present from birth but spasticity with hyperreflexia may also be seen. Brain imaging may show a thin corpus callosum as well as olivopontocerebellar hypoplasia. The ventricles are frequently enlarged. Patients are frequently irritable with few spontaneous movements.
Genitalia can be ambiguous and are frequently assigned to the female gender because of microphallus, fused scrotum, absent testes, and absence of the uterus. Many such infants are found to have XY karyotypes. Infants considered male at birth may subsequently show regression of penile corporeal tissue and may have genitalia that more closely resemble the female gender. Pelvic imaging and laparoscopy, however, may reveal a uterus, Fallopian tubes and a blind-ending vagina with no gonadal tissue even in individuals with XY karyotypes.
Genetics
Inheritance
Homozygous or compound heterozygous mutations in the TOE1 gene (1p34.1) are responsible for this condition.
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.