OMIM ID:
Brittle Cornea Syndrome 2
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Corneal thinning and extreme fragility are characteristic of BCS2. Ruptures of the cornea may occur with minimal trauma and repair is often unsatisfactory due to the lack of healthy tissue. Keratoconus, acute hydrops, keratoglobus, and high myopia are frequently present as well. Some patients have sclerocornea that obscures the normal limbal landmarks. The sclera is also thin and the underlying pigmented uveal tissue imparts a bluish discoloration to the globe which is especially evident in the area overlying the ciliary body creating what some call a blue halo.
Systemic Features
Skin laxity with easy bruisability, pectus excavatum, scoliosis, congenital hip dislocation, a high arched palate, mitral valve prolapse and recurrent shoulder dislocations are often present. Hearing impairment with mixed sensorineural/conductive defects is common.
Genetics
Inheritance
This autosomal recessive disorder results from homozygous mutations in PRDM5 (4q27). Heterozygous carriers may have blue sclerae, small joint hypermobility, and mild thinning of the central cornea.
BCS2 has many clinical similarities to brittle cornea syndrome 1 (229200) which results from homozygous mutations in ZNF469.
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.