Duane-radial ray syndrome

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Disease Profile

US Estimated

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.8

Inheritance

DRRS is inherited in an autosomal dominant manner.^[1]^[2] This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition.

In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation.

When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Okihiro syndrome; DR syndrome; Duane anomaly with radial abnormalities and deafness;

Summary

Duane-radial ray syndrome (DRRS) 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). Other features include bone abnormalities in the hands (malformed or absent thumbs, an extra thumb, or a thumb that looks like a finger) and partial or complete absence of bones in the forearm. Together, these hand and arm abnormalities are called radial ray malformations. DRRS is caused by mutations in the SALL4 gene and is inherited in an autosomal dominant manner.^[1]^[2] Treatment of DRRS may include surgery to correct Duane anomaly and radial ray malformations.^[2]

Symptoms

DRRS is characterized by a particular problem with eye movement called Duane anomaly (also known as Duane syndrome). Duane anomaly results from the improper development of certain nerves that control eye movement. This condition limits outward eye movement (toward the ear), and in some cases may limit inward eye movement (toward the nose). As the eye moves inward, the eye opening becomes narrower and the eyeball may pull back (retract) into its socket. Duane syndrome may be unilateral (affecting only one eye) or bilateral (affecting both eyes).^[1]^[3]

Bone abnormalities in the hands include malformed or absent thumbs, an extra thumb, or a 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 called radial ray malformations.

People with DRRS may have a variety of other signs and symptoms including unusually shaped ears, hearing loss, heart and kidney defects, a distinctive facial appearance, an inwardand downward-turning foot (a clubfoot), and fused spinal bones (vertebrae).^[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms	Other Names	Learn More: HPO ID
5%-29% of people have these symptoms
Slit-like opening of the exterior auditory meatus		0008588
1%-4% of people have these symptoms
Duane anomaly		0009921
Microphthalmia	Abnormally small eyeball	0000568
Percent of people who have these symptoms is not available through HPO
Abnormal nasopharynx morphology		0001739
Absent radius	Missing outer large bone of forearm	0003974
Absent thumb	Absent thumbs	0009777
Aganglionic megacolon	Enlarged colon lacking nerve cells	0002251
Anal atresia	Absent anus	0002023
Anal stenosis	Narrowing of anal opening	0002025
Aplasia of metacarpal bones	Absent long bone of hand	0010048
Atrial septal defect	An opening in the wall separating the top two chambers of the heart Hole in heart wall separating two upper heart chambers [ more ]	0001631
Autosomal dominant inheritance		0000006
Cataract	Clouding of the lens of the eye Cloudy lens [ more ]	0000518
Choanal atresia	Blockage of the rear opening of the nasal cavity Obstruction of the rear opening of the nasal cavity [ more ]	0000453
Choanal stenosis	Narrowing of the rear opening of the nasal cavity	0000452
Crossed fused renal ectopia		0004736
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
Facial asymmetry	Asymmetry of face Crooked face Unsymmetrical face [ more ]	0000324
Facial palsy	Bell's palsy	0010628
Fused cervical vertebrae	Fused neck	0002949
Horseshoe kidney	Horseshoe kidneys	0000085
Hydronephrosis		0000126
Hypertelorism	Wide-set eyes Widely spaced eyes [ more ]	0000316
Hypoplasia of the radius	Underdeveloped outer large forearm bone	0002984
Hypoplasia of the ulna	Underdeveloped inner large forearm bone	0003022
Impaired convergence		0000619
Impaired ocular abduction		0000634
Impaired ocular adduction		0000542
Iris coloboma	Cat eye	0000612
Optic disc hypoplasia		0007766
Palpebral fissure narrowing on adduction		0000661
Pectoralis hypoplasia	Small pec muscle Underdeveloped pec muscle [ more ]	0008998
Pes planus	Flat feet Flat foot [ more ]	0001763
Preaxial polydactyly		0100258
Radial deviation of the hand		0009486
Renal agenesis	Absent kidney Missing kidney [ more ]	0000104
Renal hypoplasia	Small kidneys Underdeveloped kidneys [ more ]	0000089
Renal malrotation	Abnormal rotation of the kidneys	0004712
Retinal coloboma	Hole in the back of the eye	0000480
Sandal gap	Gap between 1st and 2nd toes Gap between first and second toe Increased space between first and second toes Sandal gap between first and second toes Wide space between 1st, 2nd toes Wide space between first and second toes Wide-spaced big toe Widely spaced 1st-2nd toes Widely spaced first and second toes Widened gap 1st-2nd toes Widened gap first and second toe [ more ]	0001852
Scoliosis		0002650
Sensorineural hearing impairment		0000407
Short humerus	Short long bone of upper arm Short upper arms [ more ]	0005792
Short thumb	Short thumbs Small thumbs [ more ]	0009778
Small thenar eminence		0001245
Spina bifida occulta		0003298
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
Syndactyly	Webbed fingers or toes	0001159
Triphalangeal thumb	Finger-like thumb	0001199
Upper limb muscle hypoplasia	Underdevelopment of upper limb muscles	0009016
Vascular dilatation	Wider than typical opening or gap	0002617
Ventricular septal defect	Hole in heart wall separating two lower heart chambers	0001629
Vesicoureteral reflux		0000076

Do you have updated information on this disease? We want to hear from you.

Cause

DRRS is caused by mutations in the SALL4 gene. The SALL4 gene is part of a group of genes called the SALL family. These genes provide instructions for making proteins that are involved in the formation of tissues and organs before birth. SALL proteins act as transcription factors, which means they attach (bind) to specific regions of DNA and help control the activity of particular genes. Mutations in the SALL4 gene prevent one copy of the gene in each cell from making any protein. It remains unclear how a reduction in the amount of SALL4 protein leads to Duane anomaly, radial ray malformations, and the other features of DRRS.^[1]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment

The treatment of DRRS may vary and often requires a team of specialists. Severe strabismus associated with Duane syndrome and malformations of the hands and forearms may require eye surgery. Individuals with heart defects may also require corrective surgery. Hearing aids may be needed for those with hearing deficits. Growth hormone therapy may additionally be considered for individuals with short stature. Since kidney issues may develop, renal monitoring should also be considered.^[2]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Birth Defect Research for Children, Inc.
976 Lake Baldwin Lane, Suite 104
Orlando, FL 32814
Telephone: +1-407-895-0802
E-mail: staff@birthdefects.org
Website: https://www.birthdefects.org/

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

The Engle Laboratory provides information about Duane-radial ray syndrome and the SALL4 gene.
Genetics Home Reference (GHR) contains information on Duane-radial ray syndrome. This website is maintained by the National Library of Medicine.
The National Human Genome Research Institute (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Duane-radial ray syndrome. Click on the link to view a sample search on this topic.

References

Duane-radial ray syndrome. Genetics Home Reference (GHR). December 2009; https://ghr.nlm.nih.gov/condition/duane-radial-ray-syndrome.
Kohlhase J. SALL4-Related Disorders. GeneReviews. January 15, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1373.
Verma A. Duane Syndrome. Medscape. December 1, 2015; https://emedicine.medscape.com/article/1198559-overview.

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Neonatal

Q87.8

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Testing Resources

Treatment

Organizations

Organizations Supporting this Disease

Learn more

Where to Start

In-Depth Information

References

Rare Nephrology & Urology News

Rare Nephrology & Urology News

Neonatal

Q87.8

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Testing Resources

Treatment

Organizations

Organizations Supporting this Disease

Learn more

Where to Start

In-Depth Information

References

Rare Nephrology
& Urology News

Rare Nephrology
& Urology News

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.