OMIM ID:
Microphthalmia with Limb Anomalies
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Patients have either microphthalmia or anophthalmia which may be present unilaterally or bilaterally. The MRI in several patients has revealed complete absence of the globes, optic nerves, chiasm, and optic tracts. The eyelashes are often sparse with shortened palpebral fissures and broad lateral eyebrows.
Systemic Features
Global developmental delays, failure to thrive, and mild to moderate mental retardation are common. Syndactyly, polydactyly, and oligodactyly with hypoplasia of the long bones are present to a variable degree. Synostosis in the digits, ankles, and wrist is often seen. A split hand (lobster-claw deformity) is variably present. Other anomalies such as the kidneys (horseshoe kidney), undescended testes, anomalous venous circulation and deformed vertebrae have been reported. The midface is often flattened. A high palate, cleft lip, and mild scoliosis may be seen.
Genetics
Inheritance
This is an autosomal recessive disorder resulting from homozygous mutations in the SMOC1 gene (14q24.2) but there is some evidence of genetic heterogeneity as the disorder has been mapped to 10p11.23 in several families. However, no causative mutations were found in this region. Consanguinity among parents is common.
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.