Dubowitz syndrome is a very rare genetic and developmental disorder involving multiple congenital (inherited) anomalies including but not limited to: (1) growth failure/short stature; (2) unusual but characteristic facial features; (3) a small head (microencephaly); (4) mild (usually) mental retardation; and (5), in at least 50% of the cases, eczema. Multiple organ systems are affected and the disorder is unpredictable and extremely variable in its expression. Symptoms may be detected while the fetus is still in the uterus (intrauterine) as well as immediately after birth (neonatal).
Facial appearance is a key to the diagnosis, with characteristic high or sloping forehead; sparse hair; flat, undeveloped (hypoplastic) bones above the eyes (supraorbital ridges); increased distance between the eyes (ocular hypertelorism); drooping eyelids (ptosis); sparse (hypoplastic) lateral eyebrows; very small lower jaw (micrognathia) and receding chin (retrognathia). Affected children are often hyperactive, stubborn and shy.
Although there is great variability in the signs and symptoms associated with Dubowitz syndrome, they may include drooping eyelid (ptosis); abnormally wide space between eyelids (telecanthus); a small head (microcephaly); an abnormal cry or voice; short stature/dwarfism; small jaw and receding chin (micrognathia/retrognathia); behavior disorder/autism; intrauterine growth retardation; decreased distance between top and bottom eyelids combined with short eyelids held widely apart (blepharophimosis/short palpebral fissures); and sparse or absent scalp hair.
Other less frequent signs and symptoms may include eczema (especially on the face and/or behind the knees); broad nose; foot anomalies; delayed bone aging; vertical skin fold at the inner corner of the eye (epicanthic fold); a horny mass at the base of the spine (sacro-coccyx anomaly); undescended/ectopic testes; and mental retardation of various degrees of intensity, but most often mild.
Many children with Dubowitz syndrome have normal intelligence. However, memory difficulties and/or learning disabilities may occur. Affected individuals may have mild retardation, hyperactivity, and/or speech impairment. Some impairment in fine motor development and cognitive reasoning may also occur.
In addition to the signs indicated above, the medical literature indicates that Dubowitz syndrome may be accompanied by irregularities in almost any of the body’s organ systems. Gastrointestinal, immunological, metabolic, hematological and oncologic abnormalities have been reported.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dubowitz syndrome is probably, but not certainly, caused by a single defective gene. That gene has not yet been identified. Until recently, most clinicians and geneticists believed that Dubowitz syndrome was transmitted as an autosomal recessive trait. However, some medical researchers believe the disorder might instead be transmitted as an autosomal dominant trait.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Dubowitz Syndrome is a rare disorder that affects males and females in equal numbers. A 1996 report mentioned 141 confirmed cases. By 2002, the numbers had increased to over 200. It is believed that there are many cases in the USA and worldwide that have not been diagnosed or reported.
The diagnosis is usually based upon clinical determination made by a geneticist (dysmorph-ologist) or physician. It is based on the patient's medical history, growth data and especially the characteristic facial appearance.
Treatment of Dubowitz syndrome is symptomatic and supportive. A team approach may be of benefit for children with this disorder and may include special education, physical therapy, and other medical, social, or vocational services. Skin problems such as eczema should be treated by a dermatologist and regular dental care may be necessary to avoid serious dental problems. Genetic counseling may be of benefit for affected individual and their families.
Research on genetic disorders and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why genes sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic and familial disorders in the future.
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Opitz JM. Dubowitz Syndrome. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:179-80.
Gorlin RJ, Cohen MMJr, Levin LS. Eds. Syndromes of the Head and Neck. 3rd ed. Oxford University Press, London, UK; 1990:304-05.
Jones KL. Ed. Smith’s Recognizable Patterns of Human Malformation. 5th ed. W. B. Saunders Co., Philadelphia, PA; 1997:102-03.
Al-Nemri AR, Kilani RA, Salih MA, et al. Embryonal rhabdomyosarcoma and chromosomal breakage in a newborn infant with possible Dubowitz Syndrome. Am J Med Genet. 2000;92:107-10.
Vogels A, Lorenzetti ME, Gillis P, et al. Facial asymmetry, cardio-vascular anomalies and adducted thumbs as unusual symptoms in Dubowitzsyndrome? Ann Genet. 1996;39:31-34.
Wallerstein R, Kacmar J, Anderson CE, et al. Dubowitz syndrome in a boy without developmental delay: further evidence for phenotypic variability. Am J Med Genet. 1997;68:216-18.
Tsukahara m, Opitz JM. Dubowitz syndrome: review of 141 cases including 36 peviously unreported patients. Am J Med Genet. 1996;63:277-89.
Antoniades K, Hatzistilianou M, Pitsavas G, et al. Co-existence of Dubowitz and hyper-Ig syndromes: a case report. Eur J Pediatr. 1996;155:277-89.
FROM THE INTERNET
McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 223370: Last Edit Date; 10/11/2000.
Dubowitz Syndrome. Dubowitz Syndrome Information and Parents Group. 2002.
What is Dubowitz Syndrome. Part 2. First descriptions – 2pp.
What is Dubowitz Syndrome. Part 3. Diagnosis – 4pp.
What is Dubowitz Syndrome. Part 4. Frequent Physical Characteristics – 2pp.
What is Dubowitz Syndrome. Part 5. Occasional features – 2pp.
What is Dubowitz Syndrome. Part 6. Cause and prevalence – 2pp
What is Dubowitz Syndrome. Part 7. Behavioral and cognitive features – 3pp.
What is Dubowitz Syndrome. Part 8. Medical problems – 6pp.
What is Dubowitz Syndrome. Part 9. References/bibliography. 7pp.
Dubowitz syndrome 1. United States National Library of Medicine. Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes. Last Updated: 27 October 1999.
www.nlm.nih.gov/mesh/jablonski/syndromes/syndrome272.html (Short Version)
www.nlm.nih.gov/cgi/jablonski/syndrome_cgi?index=272 (Full Record)
Tsukahar M. Dubowitz syndrome. Orphanet. December, 2002. 1p.
List of clinical signs. Dubowitz syndrome. Orphanet. nd. 1p
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