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Genetics Home Reference: your guide to understanding genetic conditions
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Ophthalmo-acromelic syndrome

Reviewed March 2014

What is ophthalmo-acromelic syndrome?

Ophthalmo-acromelic syndrome is a condition that results in malformations of the eyes, hands, and feet. The features of this condition are present from birth. The eyes are often absent or severely underdeveloped (anophthalmia), or they may be abnormally small (microphthalmia). Usually both eyes are similarly affected in this condition, but if only one eye is small or missing, the other eye may have a defect such as a gap or split in its structures (coloboma).

The most common hand and foot malformation seen in ophthalmo-acromelic syndrome is missing fingers or toes (oligodactyly). Other frequent malformations include fingers or toes that are fused together (syndactyly) or extra fingers or toes (polydactyly). These skeletal malformations are often described as acromelic, meaning that they occur in the bones that are away from the center of the body. Additional skeletal abnormalities involving the long bones of the arms and legs or the spinal bones (vertebrae) can also occur. Affected individuals may have distinctive facial features, an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate), or intellectual disability.

How common is ophthalmo-acromelic syndrome?

The prevalence of ophthalmo-acromelic syndrome is not known; approximately 35 cases have been reported in the medical literature.

What genes are related to ophthalmo-acromelic syndrome?

Mutations in the SMOC1 gene cause ophthalmo-acromelic syndrome. The SMOC1 gene provides instructions for making a protein called secreted modular calcium-binding protein 1 (SMOC-1). This protein is found in basement membranes, which are thin, sheet-like structures that support cells in many tissues and help anchor cells to one another during embryonic development. The SMOC-1 protein attaches (binds) to many different proteins and 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 shaping (patterning) of the limbs, as well as eye formation and development. The SMOC-1 protein also likely promotes the maturation (differentiation) of cells that build bones, called osteoblasts.

SMOC1 gene mutations often result in a nonfunctional SMOC-1 protein. The loss of SMOC-1 could disrupt growth factor signaling, which would impair the normal development of the skeleton, limbs, and eyes. These changes likely underlie the anophthalmia and skeletal malformations of ophthalmo-acromelic syndrome. It is unclear how SMOC1 gene mutations lead to the other features of this condition.

Some people with ophthalmo-acromelic syndrome do not have an identified mutation in the SMOC1 gene. The cause of the condition in these individuals is unknown.

Related Gene(s)

Changes in this gene are associated with ophthalmo-acromelic syndrome.

  • SMOC1

How do people inherit ophthalmo-acromelic syndrome?

This condition 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.

Where can I find information about diagnosis or management of ophthalmo-acromelic syndrome?

These resources address the diagnosis or management of ophthalmo-acromelic syndrome and may include treatment providers.

  • Genetic Testing Registry: Anophthalmos with limb anomalies (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0599973)

You might also find information on the diagnosis or management of ophthalmo-acromelic syndrome in Educational resources (http://ghr.nlm.nih.gov/condition/ophthalmo-acromelic-syndrome/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/ophthalmo-acromelic-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about ophthalmo-acromelic syndrome?

You may find the following resources about ophthalmo-acromelic syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for ophthalmo-acromelic syndrome?

  • anophthalmia-syndactyly
  • anophthalmia-Waardenburg syndrome
  • anophthalmos-limb anomalies syndrome
  • anophthalmos with limb anomalies
  • microphthalmia with limb anomalies
  • OAS
  • ophthalmoacromelic syndrome
  • syndactyly-anophthalmos syndrome
  • Waardenburg anophthalmia syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about ophthalmo-acromelic syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding ophthalmo-acromelic syndrome?

anophthalmia ; anophthalmos ; autosomal ; autosomal recessive ; basement membranes ; calcium ; cell ; cleft palate ; differentiation ; disability ; embryonic ; gene ; growth factor ; inherited ; malformation ; mutation ; oligodactyly ; palate ; polydactyly ; prevalence ; protein ; recessive ; syndactyly ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Abouzeid H, Boisset G, Favez T, Youssef M, Marzouk I, Shakankiry N, Bayoumi N, Descombes P, Agosti C, Munier FL, Schorderet DF. Mutations in the SPARC-related modular calcium-binding protein 1 gene, SMOC1, cause waardenburg anophthalmia syndrome. Am J Hum Genet. 2011 Jan 7;88(1):92-8. doi: 10.1016/j.ajhg.2010.12.002. Epub 2010 Dec 30. (http://www.ncbi.nlm.nih.gov/pubmed/21194680?dopt=Abstract)
  • Gambhir PS, Gambhir SP, Bankar SM. Ophthalmoacromelic syndrome: two further cases expanding the phenotype. Clin Dysmorphol. 2010 Apr;19(2):91-4. doi: 10.1097/MCD.0b013e328336a1a6. (http://www.ncbi.nlm.nih.gov/pubmed/20179580?dopt=Abstract)
  • Okada I, Hamanoue H, Terada K, Tohma T, Megarbane A, Chouery E, Abou-Ghoch J, Jalkh N, Cogulu O, Ozkinay F, Horie K, Takeda J, Furuichi T, Ikegawa S, Nishiyama K, Miyatake S, Nishimura A, Mizuguchi T, Niikawa N, Hirahara F, Kaname T, Yoshiura K, Tsurusaki Y, Doi H, Miyake N, Furukawa T, Matsumoto N, Saitsu H. SMOC1 is essential for ocular and limb development in humans and mice. Am J Hum Genet. 2011 Jan 7;88(1):30-41. doi: 10.1016/j.ajhg.2010.11.012. Epub 2010 Dec 30. (http://www.ncbi.nlm.nih.gov/pubmed/21194678?dopt=Abstract)
  • Rainger J, van Beusekom E, Ramsay JK, McKie L, Al-Gazali L, Pallotta R, Saponari A, Branney P, Fisher M, Morrison H, Bicknell L, Gautier P, Perry P, Sokhi K, Sexton D, Bardakjian TM, Schneider AS, Elcioglu N, Ozkinay F, Koenig R, Mégarbané A, Semerci CN, Khan A, Zafar S, Hennekam R, Sousa SB, Ramos L, Garavelli L, Furga AS, Wischmeijer A, Jackson IJ, Gillessen-Kaesbach G, Brunner HG, Wieczorek D, van Bokhoven H, Fitzpatrick DR. Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg Anophthalmia) syndrome in humans and mice. PLoS Genet. 2011 Jul;7(7):e1002114. doi: 10.1371/journal.pgen.1002114. Epub 2011 Jul 7. (http://www.ncbi.nlm.nih.gov/pubmed/21750680?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2014
Published: January 27, 2015