The prevalence of anophthalmia-syndactyly syndrome is unknown, but approximately 35 cases have been reported in the medical literature. Most individuals with the disorder have descended from the same ancestor (founder effect).

Anophthalmia-syndactyly syndrome is an autosomal recessive disorder resulting from alterations (mutations) in the SMOC1 gene. The mutation affects the production of a protein that is thought to regulate molecules called growth factors that stimulate the growth and development of tissues throughout the body. These growth factors play important roles in skeletal formation, normal development of the limbs, as well as the proper formation and development of the eyes. However, some patients with anophthalmia-syndactyly syndrome do not have a mutation in this specific gene suggesting that alterations in other genes may cause the disorder.

Anophthalmia-syndactyly syndrome is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Symptoms of anophthalmia-syndactyly syndrome include malformations in the eyes such as underdevelopment or complete absence of the eyes. Usually, both eyes are similarly affected. In some cases, one eye may have a gap of cleft of missing tissue (coloboma). Typically, patients have poor or little to no vision.

Abnormalities in the hand and foot includes fingers and toes that are fused or webbed together (syndactyly), having fewer than five fingers or toes on a hand or foot (oligodactyly), having more than five fingers or toes on a hand or foot (polydactyly), and abnormally short fingers or toes (brachydactyly). These skeletal malformations are often described as acromelic, meaning that they occur in the bones that are away from the center of the body. Traits of the disease are present from birth.

Developmental milestones such as a responsive smile are often delayed and most patients have moderate to severe intellectual deficiencies. Facial features can include flattened midface, sparse eyelashes, high palate and cleft lip. Kidney, venous and vertebral anomalies have also been reported in rare cases. Early postnatal/perinatal death has occurred in several cases.

Diagnosis of anophthalmia-syndactyly syndrome is based on the presence of characteristic clinical findings, and possibly genetic tests. Identifying a mutation in the SMOC1 gene through molecular genetic testing can confirm diagnosis in certain cases.

Diagnostic tests for anophthalmia-syndactyly syndrome are typically genetic tests that look for mutations in the gene SMOC1. Tests such as genetic sequencing panels and clinical test for eye disorders and limb anomalies are used. Prenatal testing via CVS or amniocentesis is also possible if the causative mutation in a family has been identified. As well, ultrasound can also be utilized to identify the limb anomalies associated with anophthalmia-syndactyly syndrome before birth (prenatally).

Specialized imaging techniques such as 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 extraocular muscles.

There is currently no cure for anophthalmia-syndactyly syndrome. Treatments include surgery to correct limb anomalies or eye malformations. For an abnormally small eye or absence or underdevelopment of the eyes, children may be seen by an eye specialist (ophthalmologist), an oculoplastic surgeon, and an ocularist, who is a physician that specializes in prosthetic devices for the eyes. These physicians may perform procedures that expand the eyelids, socket and orbital bones, often by using a plastic shell-like device called a conformer, which is placed within the eye socket. A conformer can help ensure the proper development of the eye socket and bones of the face. As a child grows older, artificial (prosthetic) eyes can be created.

Children with microphthalmia who retain some vision may benefit from visual aids.

Surgical correction of limb malformations could help with mobility.

From birth, the quality of life of patients will be affected due to traits of visual impairment, limb malformations, and potential intellectual disability. Corrective surgical procedures could be used to aid with physical abnormalities and special education may be necessary.

Though there is no treatment, surgery could be used to correct physical abnormalities, aid with improving vision and mobility issues. Seek support from family, friends and support groups.

Abouzeid H, Boisset G, Favez T, et al. Mutations in the SPARC-related modular calcium-binding protein 1 gene, SMOC1, cause waardenburg anophthalmia syndrome. Am J Hum Genet. 2011;88(1):92-98.

Okada I, Hamanoue H, Terada K, et al. SMOC1 is essential for ocular and limb development in humans and mice. Am J Hum Genet. 2011;88(1):30-41.

GHR: http://ghr.nlm.nih.gov/condition/ophthalmo-acromelic-syndrome

NCBI: http://www.ncbi.nlm.nih.gov/gtr/conditions/C0599973/

OMIM: http://www.omim.org/entry/206920

Orphanet: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1106

University of Arizona: http://disorders.eyes.arizona.edu/category/alternate-names/anophthalmia-syndactyly