OMIM ID:
Cataracts, Congenital, with Brain Hemorrhage and Subependymal Calcification
Defective Genes
Clinical Characteristics
Ocular Features
Bilateral neonatal leukocoria secondary to dense congenital cataracts (not further characterized) is evident at birth. Microphthalmia and pale optic discs have each been reported in a single patient.
Systemic Features
Newborns have catastrophic intracranial hemorrhages with massive cystic destruction of white matter and basal ganglia. Subependymal calcification can be seen on CT scans. Most individuals do not live beyond the neonatal period or early infancy. Hyperreflexia, seizures, and spasticity are frequent clinical features. Some patients have hepatomegaly and mild renal anomalies in size and location. The forehead may be prominent and sloping.
Genetics
Inheritance
This is an autosomal recessive disorder resulting from homozygous mutations in the JAM3 (junctional adhesion molecule 3) gene (11q25). The gene product is one of a family of proteins that contributes to intercellular tight junctions between epithelial cells, among others, and is postulated to be important to vascular permeability as well as lens development.
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.