Clinical Characteristics
Ocular Features
Cryptophthalmos is always present. The anterior chamber was described as 'abnormal' in several stillborn male fetuses.
Systemic Features
Low-set simple ears were noted in two stillborn fetuses. Micrognathia and a broad and beaked nose with notched alae nasi were described together with a malformed and atretic larynx. The fingers and toes may be short and cutaneous syndactyly may be present. The position of the anus may be abnormal. The lungs may have abnormal lobulation and appear hyperplastic and hyperechogenic. The bladder and kidneys may be absent.
Genetics
Inheritance
Homozygous mutations in the GRIP1 gene (12q14.3) have been identified in this autosomal recessive condition.
Fraser syndrome 1 (219000) results from homozygous mutations in the FRAS1 gene.
Fraser syndrome 2 (617666) is caused by homozygous mutations in the FREM2 gene.
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.