• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report

Dubowitz Syndrome


Last updated: July 17, 2019
Years published: 1986, 1987, 1990, 1994, 2003, 2007, 2019


NORD gratefully acknowledges Georgia Loucopolous, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.

Disease Overview


Dubowitz syndrome is a rare genetic condition that had been diagnosed in only 150 to 200 people. It can be diagnosed before and after birth based on specific symptoms. These symptoms include small stature (can be seen during pregnancy), slow growth, small head (microcephaly), intellectual disability, eczema, frequent infections, and unusual and specific facial features. These facial features include a narrow or triangle- shaped face, a high or sloping forehead, undeveloped bones around the eyes (hypoplastic supraorbital ridges), droopy eyes (ptosis) that make the eyes look wide and narrow (blepharophimosis), large ears that are placed low on the head, and sparse hair and eyebrows. Other symptoms sometimes seen in this condition include unusual fingers and toes, differences in the skeleton, and poorly formed testicles and penis, or vagina. People can also have problems with their digestive system, heart, nerves, and muscles. Sometimes, people with Dubowitz syndrome develop cancer, especially in the blood (leukemia) or lymph nodes (lymphoma). The exact cancer risk is not known. People with this condition might have behavior problems, such as aggression, difficulty sleeping or eating, and ADHD (attention deficit/ hyperactivity disorder).

Some of the structural symptoms of Dubowitz syndrome can be treated through surgery. Specific medications can help treat some of the behavior problems, and the eczema. Growth hormone might help speed up growth. Speech therapy and extra help in school can help treat the intellectual disability. Physical therapy and occupational therapy may also help the child learn self-help skills. The type of cancer treatment depends on which type of cancer the person has.


Dubowitz syndrome was first discovered by Dr. Victor Dubowitz in 1965. Since then, no common genetic cause has been discovered. Researchers have found many different genetic abnormalities that can cause Dubowitz syndrome. For this reason, a few researchers wonder if this is a true genetic condition, or if it is just a group of symptoms that often appear together. However, most researchers still believe that it is a genetic condition that can be passed down through the family.

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  • Intrauterine Dwarfism
  • dwarfism-eczema-peculiar facies syndrome
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Signs & Symptoms

While there are some differences in the types and severity of symptoms that a person can have, people with Dubowitz syndrome share a few common symptoms. Almost everyone has short stature and slow growth. This can be seen before birth in an ultrasound. It can also be seen after birth. People usually have a small head (microcephaly), with a small jaw (micrognathia). They also have mild to moderate intellectual disability. People with Dubowitz syndrome have allergies and get infections easily. About half have eczema (rough, red, itchy patches of skin). The best way to diagnose Dubowitz syndrome is through the facial features. People have a narrow or triangle-shaped face with a high or sloping forehead. The bones around their eyes haven’t fully formed (hypoplastic supraorbital ridges) and their eyes are far apart (hypertelorism). They tend to have droopy eyes (ptosis) that make the eyes look wide and narrow (blepharophimosis). Their ears are large, not fully formed, and set low on their head. Affected individuals also tend to have sparse hair and eyebrows. The roof of their mouth tends to be higher than normal (arched palate), and they may have cleft lip/palate. Hearing problems have not been reported, but vision problems such as problems seeing things up close (farsightedness) and cataracts (clouding of the eye lens) have been reported.

People with Dubowitz syndrome can have problems with their nerves, which makes their muscles weak and difficult to move properly (hypotonia). There can also be problems with the skeleton, like curved pinky fingers or toes (clinodactyly). Sometimes two toes can be fused together (syndactyly). Other skeletal problems include scoliosis, and poorly formed or missing ribs. Sometimes parts of the spine (vertebra) will be fused together, making it difficult to move. Many people with Dubowitz syndrome have problems with their immune system and have allergies and frequently get infections. The immune system problems are caused by anemia, which is when there are not enough white (and red) blood cells in the blood to fight infections. Some people have poorly formed reproductive organs (genitalia), like the penis, testes, vagina, and clitoris. In men, the testes sometimes do not descend (cryptorchidism), and the urethra may open underneath the penis instead of at the tip (hypospadias). People with this condition may also have poorly formed digestive systems, lungs, and heart. Their voice tends to be high pitched and hoarse.

It is not possible to predict the level of intellectual disability; however, it is possible for someone to have normal intelligence. Severe intellectual disability is rare in this condition. Children with Dubowitz syndrome may learn self-help skills later than other children of the same age, such as dressing, eating, and going to the bathroom. They may also have delays in speech development. They may have difficulty learning in school and may have to stay behind a few grades. They may also have behavior problems, like being constantly active and disruptive (hyperactivity). They may have problems focusing and throw temper tantrums. Many children are diagnosed with ADHD. Children may also have problems sleeping and eating. It is important that children with Dubowitz syndrome eat because they are already growing slowly and they need the nutrition to grow.

Dubowitz syndrome increases the chances of having specific cancers. The exact cancer risk is not known. Blood cancers like leukemia, and lymph node cancers (lymphomas) are common. People can also get cancers like nerve cell cancer (neuroblastoma), muscle cancer (myosarcoma), and sarcomas (soft tissue/ bone cancers).

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The cause of Dubowitz syndrome is not known. Some affected individuals have changes (mutations) in the NSUN4 and LIG4 genes, while others have had small additions or deletions of DNA (microduplications/ microdeletions).

Research suggests that this condition can be passed through family in an autosomal recessive manner. We each inherit two copies of all our genes, one from our mom and one from our dad. Sometimes genes have mutations that stop them from work properly. If both copies of a specific gene don’t work properly, the person has a specific autosomal recessive genetic condition. If an individual has one normal gene and one non-working gene, the person will be a carrier for the condition, but usually will not show symptoms. The chance of two carrier parents having an affected child is 25% with each pregnancy. The chance of having a child who is also a carrier is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.

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Affected populations

Males and females have an equal chance of developing Dubowitz syndrome. It can happen in people of all ethnicities and races. There are between 150 and 200 cases recorded in research articles, but researchers believe that there are more people with Dubowitz syndrome who have not been diagnosed.

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There is a debate among researchers about whether Dubowitz syndrome is a true genetic condition because specific gene mutations or genetic differences that cause the condition have not been confirmed. Some researchers believe that Dubowitz syndrome is a group of symptoms that often appear together. This makes diagnosing Dubowitz syndrome somewhat tricky because geneticists can’t order a definitive genetic test. They can only diagnose someone based on the symptoms they show, and affected people show different types of symptoms. The main symptoms that geneticists look for are short stature, slow growth, small head, specific facial features, intellectual disabilities, and eczema.

Clinical Testing and Workup
People with Dubowitz syndrome should have frequent medical checkups based on the symptoms they have. Since vision problems are common, they should visit the eye doctor once a year. Children might also visit a hormone specialist (endocrinologist) to check on their growth as they get older. They should also have blood tests often to check for anemia or potential cancer. They might also have to visit a skin specialist (dermatologist) to keep an eye on the eczema and help find a good treatment for it.

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Standard Therapies

Treatment for Dubowitz syndrome depends on the symptoms that people have. The eczema can be difficult to treat because half of people find that corticosteroid cream (which is often used to treat eczema) doesn’t work for them. The dermatologist can help determine what works best to treat the eczema. Glasses or contact lenses help with vision problems. Cataracts (clouding of the lens) in the eye must be removed surgically. Surgery can also correct many skeletal problems, especially with the fingers, hands, and feet. Some facial features can also be corrected with surgery, such as cleft palate and droopy eyes. In some people, taking extra growth hormone helped to speed up growth. If cancer is present, the type of cancer treatment depends on which type of cancer the person has.

While there is no treatment for the intellectual disabilities, there are a few things that can help. Children do better when they have frequent sessions of speech therapy and special help or tutoring with school subjects. Occupational therapy or physical therapy may also help teach children self-help skills. Behavioral problems, like ADHD, refusal to eat, or temper tantrums, can be treated with medication or with behavioral therapy.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/ All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

Some current clinical trials also are posted on the following page on the NORD website:

For information about clinical trials sponsored by private sources, contact: http://www.centerwatch.com/

For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/

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Opitz JM. Dubowitz Syndrome. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:179-80.

Urquhart JE, Williams SG, Bhashkar SS, Bowers N, Clayton-Smith J, Newman WG. Deletion of 19q13 reveals clinical overlap with Dubowitz syndrome. Journal of Human Genetics. 2015; 60: 781-5.

Urquhart JE, Williams SG, Bhashkar SS, Bowers N, Clayton-Smith J, Newman WG. Deletion of 19q13 reveals clinical overlap with Dubowitz syndrome. Journal of Human Genetics. 2015; 60: 781-5.

Chehade C, Awwad J, Yazbeck N, Majdalani M, Wakim R, Tfayli H, et al. Dubowitz syndrome: common findings and peculiar urine odor. Application of Clinical Genetics. 2013; 6: 87-90.

Huber RS, Houlihan D, Filter K. Dubowitz syndrome: a review and implications for cognitive, behavioral, and psychological features. Journal of Clinical Medicine Research. 2011; 3(4): 147-55.

Dubowitz syndrome. Genetic and Rare Diseases Information Center website. Updated 6/7/2018. https://rarediseases.info.nih.gov/diseases/6290/dubowitz-syndrome Accessed May 9, 2019.

Dubowitz syndrome. Orphanet website. Updated June 2014. Accessed November 2018. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=235 Accessed May 9, 2019.

McKusick VA. Dubowitz syndrome. Online Mendelian Inheritance in Man (OMIM) website. The Johns Hopkins University. Updated 5/11/2010. https://www.omim.org/entry/223370 Accessed May 9, 2019.

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Programs & Resources

RareCare® Assistance Programs

NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.

Additional Assistance Programs

MedicAlert Assistance Program

NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.

Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

Rare Disease Educational Support Program

Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.

Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Rare Caregiver Respite Program

This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.

Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

Patient Organizations

NORD Breakthrough Summit | Rare Disease Conference