Rare Pulmonology News

Disease Profile

Duane-radial ray syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

Q87.8

Inheritance

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

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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

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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.

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

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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.

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Not applicable

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Other names (AKA)

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

Categories

Congenital and Genetic Diseases

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

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

      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

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

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