Duane-Radial Ray Syndrome - Causes, Symptoms, and Management

Introduction

Duane-radial ray syndrome (DRRS) is also known as Okihiro syndrome. It is a rare multiple congenital anomaly syndrome. Duane-radial ray syndrome is caused due to genetic mutations. The characteristic feature of this syndrome is an eye movement problem called the Duane anomaly. It is a rare disease. About 125 patients from 38 families have been reported to date.

What Is Duane-Radial Ray Syndrome?

Duane-radial ray syndrome is a disorder affecting the eyes and causing abnormalities in the bones of hands and arms. The association of various congenital anomalies like Duane anomaly, radial defects, conductive hearing loss, renal abnormalities, scoliosis, and imperforate anus characterizes it.

What Are the Causes of Duane-Radial Ray Syndrome?

Duane-radial ray syndrome is caused due to genetic mutations in the gene called SALL4.

The SALL4 gene is part of the family of SALL genes responsible for providing instructions to make proteins involved in the development of organs and tissues in the fetus. The SALL4 gene is found to be essential for the development of eyes, limbs, and the heart, although the exact function of the gene is still unclear.

The inheritance pattern of Duane-radial ray syndrome is autosomal dominant, which means that only one copy of the responsible gene has mutations or pathological changes for it to cause the disease in a person.

What Are the Signs and Symptoms of Duane-Radial Ray Syndrome?

The symptoms of Duane-radial ray syndrome start to appear as a newborn. Symptoms vary among different individuals. Some of the symptoms that are associated with the syndrome are listed below.

• Eye Movement Problems- Duane anomaly is a rare strabismus in which the eye's horizontal or outward movement (towards the ear) is limited. It is observed in about 50 percent of patients affected by Okihiro syndrome. In some cases, the eye's inward movement (towards the nose) is also affected. Duane anomaly is due to the faulty development of the nerves that control eye movements.

• Hand and Arm Abnormalities - Abnormalities in the hands and arms, called radial ray defects, are observed in more than 90% of the affected patients. These defects may be uni or bilateral. Radial ray malformations seen include one or more of the following symptoms.

  • Partially formed or absent thumbs.

  • Thenar hypoplasia.

  • Hypoplasia or aplasia of the radial bone(one of the two long bones in the forearm).

  • Hypoplasia of the ulna and humerus in some cases.

  • Triphalangeal thumbs. (thumbs with three phalanges).

  • Pre-axial polydactyly (thumb duplication or bifid thumb).

• Hearing Loss - conductive deafness is present in about 30% of the patients with the syndrome. Ear dysplasia may be seen along with deafness in some cases.

• Renal Abnormalities - In some cases, renal abnormalities like kidney ectopia (abnormal position), renal hypoplasia (small kidney), or horseshoe kidney may be present.

• Heart Defects - Some heart defects reported in rare cases include atrial or ventricular septal defects, conduction disturbances, or tetralogy of Fallot.

• Scoliosis - Scoliosis is observed in 10 percent of the patients affected with Duane-radial ray syndrome.

• Gastrointestinal Disorders - Rarely, gastrointestinal disorders like anal stenosis, imperforate anus, or choanal atresia may be associated with the syndrome.

• Other Symptoms - Other than the symptoms mentioned, other uncommon features may also be present. These may be as below:

  • Clubfoot.

  • Fused vertebrae.

  • Facial asymmetry, etc.

How Is Duane-Radial Ray Syndrome Diagnosed?

1. Antenatal Diagnosis.

   • Some of the Duane-radial ray syndrome features can be diagnosed during pregnancy.

   • Severe limb abnormalities, heart defects, or renal abnormalities may be observed in the ultrasound during pregnancy.

   • A genetic prenatal diagnosis is possible if the syndrome is already prevalent among the family members.

2. Postnatal Diagnosis.

• Okihiro syndrome is usually diagnosed by clinical examination and family history. Clinical evaluation includes the following.

1. A complete examination of the upper limbs is performed.
2. An ophthalmologist does an eye examination to check for eye movement problems.
3. Hearing tests are done.

• Additional imaging tests are required to check the other symptoms and to acquire a better diagnosis.MRIs and CT scans of the upper limbs, eyes, and other structures may provide information about the extent of the abnormalities.

1. Abdominal and cardiac ultrasound.
2. Complete blood count.
3. Spinal X-rays.

• When the Okihiro syndrome is suspected during clinical examination, it can be confirmed by the genetic and molecular analysis of the SALL4 gene.

How Is Duane-Radial Ray Syndrome Managed?

The treatment of Duane-radial ray syndrome is aimed at managing the symptoms and complications of the condition. The specific treatment plan for the individual depends on the extent of the abnormalities.

• Depending on the symptoms, surgery for limbs, eyes, and/or the heart may be required.

• Hearing aids and other assistive devices are used for hearing loss.

• Occupational therapy may be recommended to help individuals learn how to adapt and function with the limitations caused by the condition.

• Other treatment options that may be required include physical therapy, limb prosthesis, orthoptic reeducation, pacemaker, etc.

• Treatment of this condition requires a multidisciplinary approach, and ongoing medical care and monitoring are required in most cases.

• The syndrome has an impact on the individual's social and psychological aspects. This should be assessed and assisted.

• Pregnant women with Duane-radial ray syndrome and cardiac defects must be monitored by their cardiologist regarding the care they need during pregnancy.

• Genetic counseling should be given to affected individuals and their families. They should be informed that the chance of disease transmission from an affected individual to their offspring is 50% for each pregnancy.

What Are the Other Syndromes Similar to Duane-Radial Ray Syndrome?

The symptoms of Duane radial-ray syndrome overlap with many other syndromes like

• Holt-Oram syndrome has features like upper limb skeletal abnormalities and heart problems.

• Townes-brocks syndrome is characterized by anal opening malformation, ear abnormalities, and hand malformations affecting the thumbs.

• VACTERL association.

• Isolated Duane retraction syndrome.

• Fetal valproate syndrome.

Conclusion

The outcomes of Duane-radial ray syndrome are highly variable, depending on the severity of the clinical manifestations and their impacts on the individual's daily life. The life expectancy of the affected individual depends on the severity of the heart defects and the patient's renal function. Individuals with less severe symptoms have a good prognosis and life expectancies.