Anophthalmos with limb anomalies

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

A rare developmental disorder characterized by bilateral microphthalmia or anophthalmia, synostosis, syndactyly, oligodactyly and/or polydactyly.

The prevalence is unknown but more than 35 cases have been reported to date, mainly from consanguineous parents.

The disease presents at birth with unilateral, or more often, bilateral anophthalmia or microphthalmia and numerous limb anomalies (including synostosis, syndactyly, oligodactyly, polydactyly and long bone hypoplasia). Typically patients have clinical anophthalmia/severe microphthalmia with little/no vision. The most common limb anomalies are synostosis of the fourth and fifth metacarpals, a short 5th finger and only 4 toes bilaterally. Developmental milestones (such as responsive smile) are often delayed and most patients have moderate to severe intellectual deficiencies. Facial features can include flattened midface, sparse eyelashes, short palpebral fissures, high palate and cleft lip. Renal (horseshoe kidney), venous and vertebral anomalies have also been reported in rare cases. Early postnatal/perinatal death has occurred in several cases.

The majority of cases are caused by mutations in the SPARC-related modular calcium binding protein 1 SMOC1 gene (14q24.1) which may be involved in the regulation of bone morphogenetic proteins. The existence of other causative genes is possible but they have not yet been discovered. The FNBP4 gene (11q12.1) was identified in a case with a phenotype similar to OAS but further studies are necessary to conclude if it is indeed causative of OAS.

Diagnosis is based on the presence of characteristic clinical findings. Computed tomography (CT) scans and magnetic resonance imaging (MRI) can also be helpful in identifying the presence or absence of the globe, optic nerve and extra ocular muscles. Identifying a mutation in the SMOC1 gene confirms diagnosis.

Differential diagnoses include isolated cryptophthalmia and other forms of syndromic microphthalmia such as microphthalmia, Lenz type, oculofaciocardiodental syndrome and anophthalmia/microphthalmia-esophageal atresia (see these terms).

Prenatal testing via CVS or amniocentesis is possible if the causative mutation in a family has been identified. Ultrasound can also be utilized to identify the limb anomalies associated with OAS.

The disease is inherited autosomal recessively so genetic counseling is possible in affected families and can help in informing parents of the recurrence risk of OAS in subsequent pregnancies. If both parents are carriers there is a 25% risk with each pregnancy of having an affected child.

There is no cure for OAS. Treatment for anophthalmia/microphthalmia may be discussed with an oculoplastic surgeon and ocularist. For anophthalmia, expansion of the eyelids, socket and orbital bones is recommended as soon as possible after birth and is done via conformer therapy by an ocularist or by oculoplastic surgery using hydrogel socket expanders followed by orbital implants or dermis-fat grafts. This can help patients with achieving a more typical appearance by preventing facial deformity. Those with some vision (if the microphthalmia is not severe) may benefit from visual aids. Some limb abnormalities may also be surgically corrected to help the patient gain mobility or function, therefore orthopedic evaluation is necessary. All individuals with OAS should receive evaluation by a vision teacher and special education may be necessary.

Little is known about the prognosis given the rarity but quality of life is usually affected due to intellectual disability, visual impairment and limb anomalies.

Visit the Orphanet disease page for more resources.

Last updated: 12/1/2013

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