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Duane-radial ray syndrome

Reviewed December 2009

What is Duane-radial ray syndrome?

Duane-radial ray syndrome is a disorder that affects the eyes and causes abnormalities of bones in the arms and hands. This condition is characterized by a particular problem with eye movement called Duane anomaly (also known as Duane syndrome). This abnormality results from the improper development of certain nerves that control eye movement. Duane anomaly limits outward eye movement (toward the ear), and in some cases may limit inward eye movement (toward the nose). Also, as the eye moves inward, the eye opening becomes narrower and the eyeball may pull back (retract) into its socket.

Bone abnormalities in the hands include malformed or absent thumbs, an extra thumb, or a long thumb that looks like a finger. Partial or complete absence of bones in the forearm is also common. Together, these hand and arm abnormalities are known as radial ray malformations.

People with the combination of Duane anomaly and radial ray malformations may have a variety of other signs and symptoms. These features include unusually shaped ears, hearing loss, heart and kidney defects, a distinctive facial appearance, an inward- and upward-turning foot (clubfoot), and fused spinal bones (vertebrae).

The varied signs and symptoms of Duane-radial ray syndrome often overlap with features of other disorders. For example, acro-renal-ocular syndrome is characterized by Duane anomaly and other eye abnormalities, radial ray malformations, and kidney defects. Both conditions are caused by mutations in the same gene. Based on these similarities, researchers suspect that Duane-radial ray syndrome and acro-renal-ocular syndrome are part of an overlapping set of syndromes with many possible signs and symptoms. The features of Duane-radial ray syndrome are also similar to those of a condition called Holt-Oram syndrome; however, these two disorders are caused by mutations in different genes.

How common is Duane-radial ray syndrome?

Duane-radial ray syndrome is a rare condition whose prevalence is unknown. Only a few affected families have been reported worldwide.

What genes are related to Duane-radial ray syndrome?

Duane-radial ray syndrome results from mutations in the SALL4 gene. This gene is part of a group of genes called the SALL family. SALL genes provide instructions for making proteins that are involved in the formation of tissues and organs before birth. The proteins produced from these genes act as transcription factors, which means they attach (bind) to specific regions of DNA and help control the activity of particular genes. The exact function of the SALL4 protein is unclear, although it appears to be important for the normal development of the eyes, heart, and limbs.

Mutations in the SALL4 gene prevent cells from making any functional protein from one copy of the gene. It is unclear how a reduction in the amount of the SALL4 protein leads to Duane anomaly, radial ray malformations, and the other features of Duane-radial ray syndrome and similar conditions.

Related Gene(s)

Changes in this gene are associated with Duane-radial ray syndrome.

  • SALL4

How do people inherit Duane-radial ray syndrome?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered SALL4 gene in each cell is sufficient to cause the disorder. In many cases, an affected person inherits a mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of Duane-radial ray syndrome?

These resources address the diagnosis or management of Duane-radial ray syndrome and may include treatment providers.

  • Gene Review: SALL4-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1373/)
  • Genetic Testing Registry: Duane-radial ray syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1623209)
  • MedlinePlus Encyclopedia: Skeletal Limb Abnormalities (http://www.nlm.nih.gov/medlineplus/ency/article/003170.htm)

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

You may find the following resources about Duane-radial ray 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 Duane-radial ray syndrome?

  • DRRS
  • Okihiro 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 Duane-radial ray syndrome?

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

What glossary definitions help with understanding Duane-radial ray syndrome?

autosomal ; autosomal dominant ; cell ; clubfoot ; DNA ; dysplasia ; gene ; hypoplasia ; kidney ; mutation ; prevalence ; protein ; renal ; syndrome ; transcription

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

References

  • Al-Baradie R, Yamada K, St Hilaire C, Chan WM, Andrews C, McIntosh N, Nakano M, Martonyi EJ, Raymond WR, Okumura S, Okihiro MM, Engle EC. Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. Am J Hum Genet. 2002 Nov;71(5):1195-9. Epub 2002 Oct 22. (http://www.ncbi.nlm.nih.gov/pubmed/12395297?dopt=Abstract)
  • Borozdin W, Boehm D, Leipoldt M, Wilhelm C, Reardon W, Clayton-Smith J, Becker K, Mühlendyck H, Winter R, Giray O, Silan F, Kohlhase J. SALL4 deletions are a common cause of Okihiro and acro-renal-ocular syndromes and confirm haploinsufficiency as the pathogenic mechanism. J Med Genet. 2004 Sep;41(9):e113. (http://www.ncbi.nlm.nih.gov/pubmed/15342710?dopt=Abstract)
  • Borozdin W, Wright MJ, Hennekam RC, Hannibal MC, Crow YJ, Neumann TE, Kohlhase J. Novel mutations in the gene SALL4 provide further evidence for acro-renal-ocular and Okihiro syndromes being allelic entities, and extend the phenotypic spectrum. J Med Genet. 2004 Aug;41(8):e102. (http://www.ncbi.nlm.nih.gov/pubmed/15286162?dopt=Abstract)
  • Gene Review: SALL4-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1373/)
  • Kohlhase J, Chitayat D, Kotzot D, Ceylaner S, Froster UG, Fuchs S, Montgomery T, Rösler B. SALL4 mutations in Okihiro syndrome (Duane-radial ray syndrome), acro-renal-ocular syndrome, and related disorders. Hum Mutat. 2005 Sep;26(3):176-83. (http://www.ncbi.nlm.nih.gov/pubmed/16086360?dopt=Abstract)
  • Kohlhase J, Heinrich M, Schubert L, Liebers M, Kispert A, Laccone F, Turnpenny P, Winter RM, Reardon W. Okihiro syndrome is caused by SALL4 mutations. Hum Mol Genet. 2002 Nov 1;11(23):2979-87. (http://www.ncbi.nlm.nih.gov/pubmed/12393809?dopt=Abstract)
  • Kohlhase J, Schubert L, Liebers M, Rauch A, Becker K, Mohammed SN, Newbury-Ecob R, Reardon W. Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide embryopathy. J Med Genet. 2003 Jul;40(7):473-8. (http://www.ncbi.nlm.nih.gov/pubmed/12843316?dopt=Abstract)
  • Miertus J, Borozdin W, Frecer V, Tonini G, Bertok S, Amoroso A, Miertus S, Kohlhase J. A SALL4 zinc finger missense mutation predicted to result in increased DNA binding affinity is associated with cranial midline defects and mild features of Okihiro syndrome. Hum Genet. 2006 Mar;119(1-2):154-61. Epub 2006 Jan 3. (http://www.ncbi.nlm.nih.gov/pubmed/16402211?dopt=Abstract)
  • Terhal P, Rösler B, Kohlhase J. A family with features overlapping Okihiro syndrome, hemifacial microsomia and isolated Duane anomaly caused by a novel SALL4 mutation. Am J Med Genet A. 2006 Feb 1;140(3):222-6. (http://www.ncbi.nlm.nih.gov/pubmed/16411190?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: December 2009
Published: April 7, 2014