Duane-radial ray syndrome

Duane-radial ray syndrome is a rare genetic disorder characterized by eye movement limitations and skeletal abnormalities in the arms and hands. It is caused by mutations in the SALL4 gene and is inherited in an autosomal dominant pattern.

Overview

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.

Symptoms

The symptoms of Duane-radial ray syndrome primarily affect ocular movement and skeletal structure, though other organ systems can also be involved.

Ocular Features

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.

Skeletal and Upper Limb Features

Bone abnormalities in the hands and arms, collectively known as radial ray malformations, include:

• Malformed or underdeveloped (hypoplastic) thumbs
• An extra thumb
• A thumb that looks like a finger
• Underdevelopment or absence of the radius (the bone in the forearm)

Other Associated Features

People with the combination of Duane anomaly and radial ray malformations may have a variety of other signs and symptoms, including:

• Unusually shaped ears
• Hearing loss
• Heart and kidney defects
• A distinctive facial appearance
• An inward- and upward-turning foot (clubfoot)
• Fused spinal bones (vertebrae)

Overlapping Conditions

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, leading researchers to suspect they are part of an overlapping set of syndromes. 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.

Frequency

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

Causes & Risk Factors

Duane-radial ray syndrome results from mutations in the SALL4 gene. This gene is part of a group of genes called the SALL family, which provide instructions for making proteins involved in the formation of tissues and organs before birth. The proteins produced from these genes act as transcription factors, meaning they attach (bind) to specific regions of DNA and help 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.

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.

Inheritance

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 an affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Other Names for This Condition

• DRRS
• Okihiro syndrome