Duane-radial ray syndrome

Overview

Duane-radial ray syndrome (DRRS), also known as Okihiro syndrome, is a rare genetic condition that affects the development of the eyes and upper limbs. The disorder is characterized primarily by Duane anomaly—a type of eye movement disorder—and radial ray malformations, which are abnormalities of the bones in the arms and hands, particularly those involving the radius bone and thumbs. DRRS may also involve hearing loss, kidney abnormalities, and, in some cases, heart defects. It is part of a group of disorders called syndromic congenital cranial dysinnervation disorders (CCDDs).

Causes

Duane-radial ray syndrome is caused by mutations in the SALL4 gene, located on chromosome 20. This gene plays a key role in embryonic development, particularly in the formation of limbs and cranial nerves. The disorder is inherited in an autosomal dominant pattern, meaning a mutation in one copy of the gene is sufficient to cause the condition. However, many cases arise from de novo mutations (new mutations not inherited from a parent).

Symptoms

DRRS presents with a combination of eye and limb abnormalities, and sometimes other systemic features. Common signs and symptoms include:

• Duane anomaly: Limited horizontal eye movement, often with retraction of the eyeball into the socket when attempting inward gaze.

• Radial ray malformations: Abnormal development of the radius bone, leading to shortened forearms, absent or underdeveloped thumbs, or fusion of wrist bones.

• Hearing loss: Typically sensorineural, varying in degree.

• Kidney abnormalities: Such as renal hypoplasia or agenesis (underdeveloped or absent kidneys), which can impair kidney function.

• Congenital heart defects: Present in a minority of cases.

• Short stature and facial differences: May include a small jaw, high-arched palate, or cleft palate.

Diagnosis

Diagnosis of Duane-radial ray syndrome is based on clinical evaluation, family history, imaging studies, and genetic testing. Key diagnostic methods include:

• Ophthalmologic evaluation: To detect Duane anomaly and assess eye movement limitations.

• Radiographic imaging: X-rays of the arms and hands to reveal radial ray malformations.

• Audiological testing: To identify the extent of hearing loss.

• Renal ultrasound: To evaluate kidney structure and function.

• Genetic testing: Sequencing of the SALL4 gene confirms the diagnosis.

Family history can support diagnosis, but many cases occur sporadically with no known family history.

Treatment

There is no cure for Duane-radial ray syndrome, and treatment is individualized based on the specific symptoms and organ systems affected. Management typically involves a multidisciplinary team and may include:

• Ophthalmologic care: Monitoring and, in some cases, surgical intervention to improve eye alignment or reduce abnormal head posture.

• Orthopedic and hand surgery: To correct limb deformities, improve function, and enhance cosmetic appearance.

• Hearing aids or cochlear implants: For managing hearing loss and supporting speech development.

• Renal management: Regular monitoring of kidney function and treatment of associated complications.

• Speech and physical therapy: To support developmental milestones and communication.

• Genetic counseling: For families with known mutations or planning future pregnancies.

Prognosis

The prognosis for individuals with Duane-radial ray syndrome varies depending on the severity of the symptoms and associated anomalies. Most individuals have a normal life expectancy, especially when kidney and heart function are preserved. With appropriate medical and surgical interventions, many patients can lead independent lives and achieve good functional outcomes. Early diagnosis and comprehensive care can significantly improve quality of life and developmental outcomes.