Clinical Characteristics
Ocular Features
Cryptophthalmos, both unilateral and bilateral, is the ocular hallmark. The lid margins may be fused.
Systemic Features
Multiple systemic malformations are usually present. A small mouth, nasal dysplasia with hypoplastic alae nasi, and syndactyly may be seen. Urogenital malformations such as renal dysgenesis or dysplasia, ambiguous genitalia, streak ovaries may be present. Pulmonary hypoplasia and imperforate anus have been reported.
Genetics
Inheritance
Homozygous mutations in the FREM2 gene (13q13.3) have been identified in Fraser syndrome 2.
See Fraser syndrome 1 (219000) for additional features that may be present in Fraser syndrome.
Fraser syndrome 3 (617667) results from homozygous mutations in GRIP1.
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.