Robinow syndrome 5214835 223599202 2008-07-04T20:35:01Z 195.148.29.73 /* External links */ [[pl:Zespół Robinowa|+pl]] + commons {{Infobox_Disease | Name = Robinow syndrome | Image = Robinowsyndrome.jpg| Caption = An infant exhibiting the facial features of Robinow syndrome.| ICD10 = {{ICD10|Q|87|1|q|80}} | ICD9 = {{ICD9|759.8}}| OMIM = 180700 | }} '''Robinow syndrome''' is an extremely rare [[genetic disorder]] characterized by short-limbed [[dwarfism]], abnormalities in the head, face, and external [[sex organ|genitalia]], as well as [[vertebrae|vertebral]] segmentation. The disorder was first described in 1969 by human [[geneticist]] [[Meinhard Robinow]],<ref name="patton">{{cite journal | author=Patton M, Afzal A | title=Robinow syndrome. | url=http://jmg.bmjjournals.com/cgi/content/full/39/5/305 |journal=Journal of Medical Genetics | volume=39 | issue=5 | pages=305–310 | year=2002 | pmid=12011143 | doi=10.1136/jmg.39.5.305}} </ref> along with [[physician]]s [[Frederic N. Silverman]] and [[Hugo D. Smith]], in the ''American Journal of Diseases of Children''. By 2002, over 100 cases had been documented and introduced into medical literature.<ref name="patton" /> Two forms of the disorder exist, [[dominant gene|dominant]] and [[recessive gene|recessive]], of which the former is more common. Patients with the dominant version often suffer moderately from the aforementioned symptoms. Recessive cases, on the other hand, are usually more physically marked, and individuals may exhibit more [[skeleton|skeletal]] abnormalities.<ref name="foundation">Robinow Syndrome Foundation. ''[http://www.robinow.org/general.html General Information]''. Accessed 19 May 2006.</ref> Interestingly, the recessive form is particularly frequent in [[Turkey]].<ref name="balci">{{cite journal | author=Balci S, Beksaç S, Haliloglu M, Ercis M, Eryilmaz M | title=Robinow syndrome, vaginal atresia, hematocolpos, and extra middle finger | journal=American Journal of Medical Genetics | volume=79 | issue=1 | pages=27–29 | year=1998 | pmid=9738864 | doi=10.1002/(SICI)1096-8628(19980827)79:1<27::AID-AJMG7>3.0.CO;2-F | doilabel=10.1002/(SICI)1096-8628(19980827)79:1&#60;27::AID-AJMG7&#62;3.0.CO;2-F}}</ref> However, this can likely be explained by a [[common ancestor]], as these patients' families can be traced to a single town in Eastern Turkey.<ref name="vanbokhoven">{{cite journal | author=van Bokhoven H, Celli J, Kayserili H, van Beusekom E, Balci S, Brussel W, Skovby F, Kerr B, Percin E, Akarsu N, Brunner H | title=Mutation of the gene encoding the ROR2 tyrosine kinase causes autosomal recessive Robinow syndrome. | journal=Nature Genetics | volume=25 | issue=4 | pages=423–426 | year=2000 | pmid=10932187 | doi=10.1038/78113}}</ref> Clusters of the [[autosome|autosomal]] recessive form have also been documented in [[Oman]] and [[Czechoslovakia]].<ref name="patton" /> The syndrome is also known as '''Robinow-Silverman-Smith syndrome''', '''Robinow dwarfism''', '''fetal face''', '''fetal face syndrome''',<ref name="nord">National Organization for Rare Disorders, Inc. ''[http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Robinow%20Syndrome Robinow Syndrome]''. Last modified 15 May 2006. Accessed 19 May 2006.</ref> '''fetal facies syndrome''', '''acral dysostosis with facial and genital abnormalities''', or '''mesomelic dwarfism-small genitalia syndrome'''.<ref name="jablonski">Jablonski's Syndromes Database. ''[http://www.nlm.nih.gov/cgi/jablonski/syndrome_cgi?index=562 Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes]''. Accessed 20 May 2006.</ref> == Medical features == Robinow noted the resemblance of affected patients' faces to that of a [[fetus]], using the term "fetal facies" to describe the appearance of a small face and widely spaced eyes.<ref name="patton" /> Clinical features also may include a short, upturned nose, a prominent forehead, and a flat nasal bridge. The upper lip may be "tented,"<ref name="patton" /> exposing dental crowding, "[[ankyloglossia|tongue tie]]," or [[gingiva|gum]] [[Organ hypertrophy|hypertrophy]]. Though the eyes do not protrude, abnormalities in the lower [[eyelid]] may give that impression. Surgery may be necessary if the eyes cannot close fully. In addition, the [[ear]]s may be set low on the head or have a deformed [[pinna (anatomy)|pinna]]. Patients suffer from dwarfism, [[mesomelic brachymelia|short lower arms]], small feet, and small hands. Fingers and toes may also be [[brachydactyly|abnormally short]] and laterally or medially bent. The thumb may be displaced and some patients, notably in Turkey, experience [[ectrodactyly]].<ref name="patton" /> All patients often suffer from vertebral segmentation abnormalities. Those with the dominant variant have, at most, a single [[butterfly vertebrae|butterfly vertebra]].<ref name="foundation" /> Those with the recessive form, however, may suffer from [[hemivertebrae]], vertebral fusion, and rib anomalies. Some cases resemble [[Jarcho-Levin syndrome]] or [[spondylocostal dysostosis]]. Genital defects characteristically seen in males include a [[micropenis]] with a normally developed [[scrotum]] and [[testes]]. Sometimes, testicles may be undescended, or the patient may suffer from [[hypospadias]].<ref name="foundation" /> Female genital defects may include a reduced size [[clitoris]] and underdeveloped [[labia minora]]. Infrequently, the [[labia majora]] may also be underdeveloped.<ref name="foundation" /> Some research has shown that females may experience [[vaginal atresia]] or [[haematocolpos]].<ref name="balci" /> The autosomal recessive form of the disorder tends to be much more severe. Examples of differences are summarized in the following table:<ref name="robinow">{{cite journal | author=Robinow, M | title=The Robinow (fetal face) syndrome: a continuing puzzle. | journal=Clin Dysmorphol | volume=2 | pages=189–198 | year=1993}}</ref> {| class="wikitable" |- ! Characteristic ! Autosomal dominant ! Autosomal recessive |- | Stature | More than 2 [[standard deviation|SD]] shorter | Short or normal |- | Arms | Very short | Slightly short |- | Elbow | Radial head dislocation | No dislocation |- | Upper lip | Normal | Tented |- | Mortality rate | Normal | 10% |} == Associated conditions == Medical conditions include frequent [[ear infection]], hearing loss, [[hypotonia]], developmental problems, respiratory problems, eating difficulties, [[Photophobia|light sensitivity]], and [[esophageal reflux]].<ref name="foundation" /> Data on [[fertility]] and the development of [[secondary sex characteristics]] is relatively sparse. It has been reported that both male and female patients have had children. Males who have reproduced have all suffered from the autosomal dominant form of the disorder; the fertility of those with the recessive variant is unknown.<ref name="patton" /> Researchers have also reported abnormalities in the [[renal tract]] of affected patients. [[Hydronephrosis]] is a relatively common condition, and researchers have theorized that this may lead to [[urinary tract infection]]s.<ref name="sphrintzen">{{cite journal | author=Sphrintzen RJ, Goldberg RB, Saenger P, Sidoti EJ | title=Male to male transmission of Robinow syndrome. | journal=Am J Dis Child | volume=136 | pages=594–597 | year=1982}}</ref> In addition, a number of patients have suffered from [[cystic dysplasia]] of the [[kidney]].<ref name="patton" /> A number of other conditions are often associated with Robinow syndrome. About 15% of reported patients suffer from [[congenital heart defect]]s. Though there is no clear pattern, the most common conditions include [[pulmonary stenosis]] and [[atresia]].<ref name="webber">{{cite journal | author=Webber S, Wargowski D, Chitayat D, Sandor G | title=Congenital heart disease and Robinow syndrome: coincidence or an additional component of the syndrome? | journal=Am J Med Genet | volume=37 | issue=4 | pages=519–21 | year=1990 | pmid=2260599 | doi=10.1002/ajmg.1320370418}}</ref> In addition, though intelligence is generally normal, around 15% of patients show developmental problems.<ref name="patton" /> == Genetics == [[Genetics|Genetic]] studies have linked the autosomal recessive form of the disorder to the ''[[ROR2]]'' [[gene]] on position 9 of the long arm of [[chromosome 9 (human)|chromosome 9]].<ref name="patton" /> The gene is responsible for aspects of bone and cartilage growth. This same gene is involved in causing autosomal dominant [[brachydactyly B]].<ref name="patton" /> The autosomal dominant form has not been linked to a specific gene, though those related to ''ROR2'' are being studied. This form is often caused by new mutations. Alternatively, it may be passed from a parent who is so mildly affected by the disorder that he or she has not been diagnosed.<ref name="foundation" /> A fetal [[ultrasound]] can offer [[prenatal diagnosis]] 19 weeks into [[pregnancy]]. However, the characteristics of a fetus suffering from the milder dominant form may not always be easy to differentiate from a more serious recessive case. [[Genetic counseling]] is an option given the availability of a family history.<ref name="patton" /> == References == <div class="references-small"><references /></div> ==External links== {{commonscat|Robinow syndrome}} *{{RareDiseases|5704}} {{Phakomatoses and other congenital malformations not elsewhere classified}} [[Category:Genetic disorders]] [[Category:Rare diseases]] [[Category:Syndromes]] [[de:Robinow-Syndrom]] [[pl:Zespół Robinowa]]