Dubowitz Syndrome

Dubowitz Syndrome

Summary

Dubowitz syndrome is a very rare genetic and developmental disorder with a broad range of signs and symptoms. The typical findings of Dubowitz syndrome include growth failure/short stature, characteristic facial features such as a small triangular face, high sloping forehead, drooping eyelid (ptosis), short eyelids, increased distance between eyes (hypertelorism) broad and flat nasal bridge with a prominent and rounded nasal tip, smaller than normal head (microcephaly), intellectual disability, and eczema, especially on the face and behind the knees. Other common findings are behavioral disorders (hyperactivity, and/or autistic features), speech alterations, scanty or absent hair, foot abnormalities, delayed bone age, bone defects of the lower part of the spine (sacrum and coccyx), testicles that are still not located in the scrotum (cryptorchidism), memory and / or learning problems. There may be an increased risk of having cancer such as leukemia, or lymphoma. The diagnosis is made based on the symptoms (specially the facial features), but there is no specific laboratory test. The cause is still unknown, but, some people who are diagnosed with the syndrome may have variants in the NSUN2 and LIG4 genes, or have loss or gain of microscopic material in some chromosomes (chromosomal microdeletions or microduplications).

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).

Causes

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.

Diagnosis

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.

Treatment

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.

Type of Doctor Department :- Pediatric Rehabilitation Specialist can diagnose Dubowitz syndrome