Duane-radial ray syndrome

Description

Duane-radial ray syndrome, also called Okihiro syndrome, is characterized by abnormalities of the bones in the arms and hands that may be associated with problems in the eyes, ears, and other organs. The particular features of the condition can vary greatly among affected individuals.

People with Duane-radial ray syndrome often have underdeveloped 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 Duane-radial ray syndrome may also have a disorder called Duane anomaly (also known as Duane retraction syndrome), which can affect one or both eyes. This condition occurs when certain nerves that control eye movement do not develop properly. Duane anomaly may limit outward eye movement (toward the ear) or inward eye movement (toward the nose). In people with this condition, the eyeball may pull back (retract) into its socket and the eyelid opening may narrow as the eye moves to the side. Because the eyes often do not look in the same direction (strabismus), affected individuals may need to turn their head to track objects with both eyes.

A variety of other signs and symptoms may be seen in people with Duane-radial ray syndrome. These can include hearing loss, unusually shaped ears, additional eye abnormalities, an inward- and upward-turning foot (clubfoot), fused spinal bones, a spine that curves to the side (scoliosis), and abnormalities of the anus and rectum (anorectal abnormalities). Affected individuals may also have heart and kidney defects.

Duane-radial ray syndrome is often considered to be part of a disease spectrum with other conditions that share similar features. Because these conditions are all caused by changes in the same gene, they are sometimes called SALL4-related disorders.

Frequency

Duane-radial ray syndrome is a rare condition, although its exact prevalence is unknown.

Causes

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the SALL4 gene cause Duane-radial ray syndrome. The SALL4 gene plays a role in the proper formation of tissues and organs before birth. This gene provides instructions for making a protein that acts as a transcription factor, which means it binds to specific regions of DNA and helps control the activity of particular genes. Although the exact function of the SALL4 protein is unclear, it appears to be important for the normal development of the eyes, heart, and limbs.

Most of the pathogenic variants in the SALL4 gene that cause Duane-radial ray syndrome are considered “loss-of-function variants” because they reduce the activity of the SALL4 protein or decrease the amount of protein that is produced by cells. While a reduction in the amount of SALL4 protein seems to affect development before birth, it is unclear why the eyes, arms, and hands are particularly affected in people with Duane-radial ray syndrome.

Inheritance

Duane-radial ray syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In many cases, an affected person inherits the pathogenic variant from a parent. Other cases result from a new (de novo) variant in the gene that occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These individuals typically have no history of the disorder in their family.

Autosomal dominant inheritance with a new (de novo) mutation. Credit: U.S. National Library of Medicine.

Other Names for This Condition

• DRRS
• Okihiro syndrome
• SALL4-related disorder

Where this page came from

This page was imported from MedlinePlus Genetics, National Library of Medicine. Courtesy of MedlinePlus from the National Library of Medicine; its genetics summaries and the illustrations credited to the library are in the public domain. Pictures credited to others are not copied.

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