Dubowitz syndrome: Difference between revisions
spelling error |
Reverted good faith edits by Giraffe73 (talk). (TW) |
||
| Line 16: | Line 16: | ||
}} |
}} |
||
'''Dubowitz syndrome''' is a rare genetic disorder characterized by [[microcephaly]], stunted growth, and a receding |
'''Dubowitz syndrome''' is a rare genetic disorder characterized by [[microcephaly]], stunted growth, and a receding chin. Symptoms vary among patients, but other characteristics include a soft, high-pitched voice; partial webbing of the fingers and toes; palate deformations; genital abnormalities; language difficulties; and an aversion to crowds.<ref name=enotes>{{cite web |url=http://health.enotes.com/genetic-disorders-encyclopedia/dubowitz-syndrome |title=Dubowitz syndrome |format= |work=Encyclopedia of Genetic Disorders |accessdate= |deadurl=yes |archiveurl=https://web.archive.org/web/20070418113047/http://health.enotes.com/genetic-disorders-encyclopedia/dubowitz-syndrome |archivedate=2007-04-18 |df= }}</ref> The pathogenesis of the disease is yet to be identified, and no medical tests can definitively diagnose the disease.<ref>{{cite web |url=http://www.ric.edu/uap/dsyndrome/research.html |title=Dubowitz Syndrome Support Network |work= |accessdate=}}</ref> The primary method of diagnosis is to identify facial phenotypes. Since it was first described in 1965 by English physician [[Victor Dubowitz]], over 140 cases have been reported worldwide. Although the majority of cases have been reported from the United States, Germany, and Russia, the disorder appears to affect both genders and all ethnicities equally.<ref name=enotes/> |
||
== Presentation == |
== Presentation == |
||
Revision as of 16:38, 8 January 2018
| Dubowitz syndrome | |
|---|---|
| Specialty | Medical genetics  |
Dubowitz syndrome is a rare genetic disorder characterized by microcephaly, stunted growth, and a receding chin. Symptoms vary among patients, but other characteristics include a soft, high-pitched voice; partial webbing of the fingers and toes; palate deformations; genital abnormalities; language difficulties; and an aversion to crowds.[2] The pathogenesis of the disease is yet to be identified, and no medical tests can definitively diagnose the disease.[3] The primary method of diagnosis is to identify facial phenotypes. Since it was first described in 1965 by English physician Victor Dubowitz, over 140 cases have been reported worldwide. Although the majority of cases have been reported from the United States, Germany, and Russia, the disorder appears to affect both genders and all ethnicities equally.[2]
Presentation
Microcephaly is a characteristic in which the circumference of the head is smaller than normal due to improper development of the brain. It is caused by genetic disorders, infections, radiation, medications or alcohol abuse during pregnancy. Defects in the growth of the cerebral cortex lead to many of the features associated with microcephaly.[4] There is currently no known method of correcting microcephaly. However, there are a variety of symptomatic treatments that help to counter some of its adverse effects, such as speech and occupational therapies, as well as medication to control seizures and hyperactivity.[5] Microcephaly has a vast range of prognoses: some patients experience little to very mental retardation and can reach regular age-appropriate milestones. Others may experience severe mental retardation and neuromuscular side effects.[4]
Genetics
 | This article may require copy editing for grammar, style, cohesion, tone, or spelling. (September 2017) |
Although the exact pathology of Dubowitz syndrome is not known yet, it is heritable and classified as an autosomal recessive disease. Furthermore, there is an occasional parental consanguinity. Several cases point to Dubowitz syndrome occurring in monozygotic twins, siblings, and cousins.[6] There is considerable phenotypic variability between cases, especially in regards to intelligence.[7] Although substantial evidence points to the genetic basis of this disorder, the phenotypic similarity is found in fetal alcohol syndrome. Further studies need to be done to determine whether this environmental agent effects the expression of the genotype.[8] Breakdown of chromosomes is known to occur.[6]
Growth hormone
Dubowitz syndrome is accompanied by a deficiency in growth hormone.[9] Individuals with this disorder have stunted growth, and growth hormones are secreted by the anterior pituitary of the brain. The main function of the anterior pituitary is to increase the height of an individual during development. The anterior pituitary also plays a role in regulating the immune function, increasing calcium retention, increasing muscle mass and stimulating gluconeogenesis. A deficiency in growth hormone may be caused by gene mutations, malformations of the hypothalamus or pituitary gland during development or damage to the pituitary.[10] In Dubowitz syndrome, the cause is likely due to the gene mutations or disruption of brain structures during development. Growth hormone deficiency also correlates with low levels of IgG, a condition found in Dubowitz patients.[6]
Relation to SLOS
Researchers are also investigating the genetic similarities between Dubowitz Syndrome and Smith-Lemli-Opitz syndrome (SLOS). Patients with SLOS and Dubowitz syndromes experience many of the same abnormalities, and the two disorders are hypothesized to be linked. A characteristic of SLOS is a low cholesterol level and a high 7-dehydrocholesterol level. Cholesterol is essential for several key functions of the body, including cell membrane structure, embryogenesis, and steroid and sex hormone synthesis. Impaired cholesterol biosynthesis or transport possibly accounts for most of the symptoms of both SLOS and Dubowitz. Although only a few patients with Dubowitz Syndrome have been identified with altered cholesterol levels, researchers are exploring whether Dubowitz Syndrome, like SLOS, carries a link to a defect in the cholesterol biosynthetic pathway.[11]
The exact biochemical pathology of the disease is still under research because of the low prevalence of the disease and the wide array of symptoms associated with it. Several studies have focused on different aspects of the disease to try to find its exact cause and expression. One study examined the specific oral features in one patient.[12] Another found abnormalities in the brain, such as corpus callosum dysgenesis, an underdeveloped anterior pituitary and a brain stalk with an ectopic neurohypophysis.[13]
Diagnosis
![[icon]](/wiki/File:Wiki_letter_w_cropped.svg){kind=small} | This section is empty. You can help by adding to it. (July 2017) |
Management
| This section is empty. You can help by adding to it. (July 2017) |
References
- ^ "Dubowitz syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 11 July 2017.
- ^ a b "Dubowitz syndrome". Encyclopedia of Genetic Disorders. Archived from the original on 2007-04-18.
{{cite web}}: Unknown parameter|deadurl=ignored (|url-status=suggested) (help) - ^ "Dubowitz Syndrome Support Network".
- ^ a b Microcephaly Information Page at NINDS
- ^ "Microcephaly - Symptoms, Treatment and Prevention". The HealthCentralNetwork.
- ^ a b c Online Mendelian Inheritance in Man (OMIM): Rasmussen, Sonja A. Dubowitz Syndrome - 223370
- ^ Ilyina HG, Lurie IW (1990). "Dubowitz syndrome: possible evidence for a clinical subtype". Am. J. Med. Genet. 35 (4): 561–5. doi:10.1002/ajmg.1320350423. PMID 2185633.
- ^ Mathieu M, Berquin P, Epelbaum S, Lenaerts C, Piussan C (December 1991). "[Dubowitz syndrome. A diagnosis not to be missed]". Arch. Fr. Pediatr. (in French). 48 (10): 715–8. PMID 1793348.
- ^ Hirano T, Izumi I, Tamura K (1996). "Growth hormone deficiency in Dubowitz syndrome". Acta Paediatr Jpn. 38 (3): 267–9. doi:10.1111/j.1442-200x.1996.tb03484.x. PMID 8741320.
- ^ "Archived copy". Archived from the original on 2007-04-24. Retrieved 2007-04-30.
{{cite web}}: Unknown parameter|deadurl=ignored (|url-status=suggested) (help)CS1 maint: archived copy as title (link) Rieser, Patricia. Growth Hormone Deficiency. 1979. 30 April 2007. - ^ Ahmad A, Amalfitano A, Chen YT, Kishnani PS, Miller C, Kelley R (1999). "Dubowitz syndrome: a defect in the cholesterol biosynthetic pathway?". Am. J. Med. Genet. 86 (5): 503–4. doi:10.1002/(SICI)1096-8628(19991029)86:5<503::AID-AJMG21>3.0.CO;2-Y. PMID 10508998.
- ^ Chan KM, King NM (2005). "Dubowitz syndrome: report of a case with emphasis on the oral features". J Dent Child (Chic). 72 (3): 100–3. PMID 16568913.
- ^ Oguz KK, Ozgen B, Erdem Z (2003). "Cranial midline abnormalities in Dubowitz syndrome: MR imaging findings". Eur Radiol. 13 (5): 1056–7. doi:10.1007/s00330-002-1580-2. PMID 12695828.