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Robinow Syndrome

Robinow's Syndrome

Robinow syndrome is an extremely rare genetic disease characterized by skeletal dysplasia, facial and genital abnormalities. The diagnosis is made based on clinical criteria and genetic testing.


Two distinct forms of Robinow syndrome are recognized in literature - autosomal recessive (caused by heterozygous mutations in the receptor tyrosine kinase-like orphan receptor 2, or ROR2, on chromosome 9) and autosomal dominant (caused by mutations in ROR2 and WTN5A gene on chromosome 3) [1]. Symptoms may begin soon after birth, and the condition affects both genders equally [2]. The clinical presentations somewhat vary, but several features are shared by both forms. Firstly, skeletal changes, such as disproportionately short limbs (mesomelic or acromesomelic), most frequently involving the forearms, brachydactyly, syndactyly, scoliosis, and vertebral segmentation is seen in both autosomal dominant and autosomal recessive subtypes [3] [4]. Additionally, hypoplasia of the midface, macrocephaly, a large and triangular mouth (V-shaped upper lip), hypertrophy of the gums, delayed loss of decidual teeth, a short and upturned nose, hypertelorism, and a prominent forehead are some of the most common facial abnormalities noted, while the presence of a micropenis or cryptorchidism and vaginal atresia or underdeveloped labia minora are notable genital changes in males and females, respectively [2] [3] [4] [5]. However, the autosomal recessive variant of Robinow syndrome generally carries a more severe presentation, with a fusion of the ribs and pronounced vertebral and other skeletal defects being important distinguishing characteristics, while supernumerary teeth and an umbilical hernia are seen only in autosomal dominant forms [2]. Involvement of other organs and tissues has been recognized as well, examples being renal disease (hydronephrosis), congenital heart disease (bicuspid aortic valve, stenosis of the pulmonary valve, atrial septal defect, ventricular septal defect, and tetralogy of Fallot), nail hypoplasia and mental delays [3] [5].

Short Stature in Children
  • Most children with Robinow syndrome experience growth delays after birth, resulting in slight to moderate short stature.[rarediseases.org]
Dysmorphic Face
  • Abstract Introduction: Robinow syndrome (RS) is an infrequent genetic condition that is characterized by a dysmorphic face, dental anomaly, short stature, mesomelic limb shortening, hand and foot anomalies, and hypoplastic genitalia.[thritajournal.com]
Accelerated Growth
  • Accelerated growth of the nose in adolescence gives the face a more normal appearance, but the broad forehead, broad nasal root, and ocular hypertelorism persist into adulthood.[ncbi.nlm.nih.gov]
Disturbance of Growth
  • Overexpression of Ror2 mutants led to a disturbance of growth plate architecture and a severe block of chondrocyte differentiation, demonstrating the functional importance of Ror2 in skeletogenesis. Copyright (c) 2006 Wiley-Liss, Inc.[ncbi.nlm.nih.gov]
  • Primary lung function is normal, but changes in the chest wall and thoracic vertebrae may reduce cough effort and predispose to respiratory infections [ Sleesman & Tobias 2003 ]. Urogenital.[ncbi.nlm.nih.gov]
Severe Abdominal Pain
  • A 14-year-old girl with Robinow syndrome was admitted with severe abdominal pain that had recurred periodically during the last 6 months.[ncbi.nlm.nih.gov]
  • abdominal pain that had recurred periodically during the last 6 months.[doi.org]
  • She had frontal balding, mid-face hypoplasia, a small nose, macrostomia with down-turned corners of the mouth, gingival hypertrophy, and hypoplasia or absence of the clitoris.[ncbi.nlm.nih.gov]
Hypoplastic Nails
  • It is characterized by mesomelic brachymelia, hemivertebrae, dysmorphic facies, genital hypoplasia, micropenis, clinodactyly, camptodactly, hypoplastic nails and moderate short stature.[ncbi.nlm.nih.gov]
Hearing Impairment
  • Bilateral conductive hearing impairment with hyperostosis of the temporal bone: a new finding in Robinow syndrome.[thritajournal.com]
  • It is characterized by growth and developmental delay, vision and hearing impairment, and impairment of the peripheral nervous system function.[icd10data.com]
Skeletal Dysplasia
  • Robinow syndrome is a skeletal dysplasia with both autosomal dominant and autosomal recessive inheritance patterns. It is characterized by short stature, limb shortening, genital hypoplasia, and craniofacial abnormalities.[ncbi.nlm.nih.gov]
  • Rob·i·now syn·drome ( rob'i-now ), [MIM*180700] a skeletal dysplasia characterized by bulging forehead, hypertelorism, depressed nasal bridge (so-called fetal face), wide mouth, acromesomelic shortening of limbs, hemivertebrae, and hypoplastic genitalia[medical-dictionary.thefreedictionary.com]
  • Robinow Syndrome (RS), a rare skeletal dysplasia syndrome, is characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, hypoplastic external genitalia in males, and renal and vertebral anomalies.[ncbi.nlm.nih.gov]
  • Locus heterogeneity characterizes a variety of skeletal dysplasias often due to interacting or overlapping signaling pathways.[ncbi.nlm.nih.gov]
  • (Limb Malformations & Skeletal Dysplasia Clinic, MSU, NRC). Date 2008 Source Samia A Temtamy, Mona S Aglan. Brachydactyly. Orphanet Journal of Rare Diseases. 3, 15. 2008.[commons.wikimedia.org]
Thumb Hypoplasia
  • Clinical manifestations included short stature, characteristic facies, mesomelic brachymelia, brachydactyly, camptodactyly, duplication of thumbs, hypoplasia of clitoris, and deformed pronated foot.[ncbi.nlm.nih.gov]
Small Scrotum
  • In males, the penis is small; scrotum and testes are normal. Cryptorchidism has been reported. In females, clitoral size is reduced; labia majora may be hypoplastic.[ncbi.nlm.nih.gov]
  • The ambiguous genitalia appearance may lead to confusion in gender assignment.[ncbi.nlm.nih.gov]
  • Nomenclature Other names by which Robinow syndrome has been known in the past: Costovertebral segmentation defect with mesomelia (COVESDEM): this name is no longer used because it causes confusion with similar vertebral defect syndromes, and in ROR2 -[ncbi.nlm.nih.gov]


Despite the fact that only about 100 cases have been reported until the end of the 20th century, the diagnosis of Robinow syndrome must be suspected in the presence of skeletal, facial and genital signs and symptoms [3] [5]. For this reason, a thorough physical examination of the newborn or infant is a necessary step in order to make an initial diagnosis. A detailed family history is equally important during workup, as similar symptoms may be encountered among relatives or close family members. Plain radiography, echocardiography, and abdominal ultrasonography can all be highly useful in the assessment of skeletal, dental, cardiac and renal defects, respectively. Detection of genetic mutations, however, is mandatory in order to confirm Robinow syndrome as the underlying cause. Severe symptoms that suggest autosomal recessive variant should prompt an investigation for ROR2 mutations, whereas autosomal dominant forms require additional testing for WNT5A gene abnormalities [5] [6]. Testing may be performed once clinical criteria are fulfilled, but a prenatal diagnosis through genetic testing during pregnancy may be obtained in the setting of a positive family history as well [4] [5].


  • The potential difficulty of detecting symptoms related to cerebral ischemia in the Robinow's population - where cognitive impairment may obscure initial neurologic symptoms - can result in delayed diagnosis and treatment.[ncbi.nlm.nih.gov]
  • We propose its association with GH deficiency and that treatment with rhGH can result in a significant increase in the growth rate of these children.[ncbi.nlm.nih.gov]
  • Treatment or Management of the Condition Treatment options are available for Robinow syndrome. The most common treatment option is surgical correction. Other treatment options are growth hormone therapy, dental therapy, and counseling.[wiki.ggc.edu]
  • The treatment varies from one patient to another depending on the present symptoms. Surgical correction of the physical deformities is the most common treatment option.[hxbenefit.com]
  • Specialized treatment often requires many families to travel in order to recieve care by specialist that have experience with this rare condition.[gofundme.com]


  • The prenatal and postnatal findings, the differential diagnosis, and the prognosis of patients with this syndrome are discussed. 2013 Wiley Periodicals, Inc. J Clin Ultrasound, 42:297-300, 2014.[ncbi.nlm.nih.gov]
  • Prognosis Prognosis of Robinow syndrome is generally good but the severity of heart disorders may affect life expectancy. The documents contained in this web site are presented for information purposes only.[orpha.net]
  • What is the Prognosis of Robinow Syndrome? (Outcomes/Resolutions) The prognosis of Robinow Syndrome is reported to be generally good with appropriate treatment measures The prognosis also depends on the severity of the signs and symptoms.[dovemed.com]
  • Robinow Syndrome Prognosis The outcome is generally positive with proper and timely treatment. Over 80% of the children with the disorder have normal intelligence and can take part in normal daily activities.[hxbenefit.com]


  • The etiology of dominant Robinow syndrome is unknown; however, the phenotypically more severe autosomal recessive form of Robinow syndrome has been associated with mutations in the orphan tyrosine kinase receptor, ROR2, which has recently been identified[ncbi.nlm.nih.gov]
  • Since the description of autosomal dominant Robinow Syndrome (ADRS; OMIM 180700) in 1969 by Meinhard Robinow and colleagues, the molecular etiology remained elusive until only recently.[ncbi.nlm.nih.gov]
  • Etiology Mutations in WNT5A gene (3p14.3) have been reported in some patients ( 10%) with autosomal dominant Robinow syndrome. Genetic counseling Transmission is autosomal dominant.[orpha.net]
  • Etiology Autosomal recessive Robinow syndrome is caused by mutations in the ROR2 gene (9q22). Mutations in the WNT5A gene (3p14.3) have been reported in some patients ( 10%) with autosomal dominant Robinow syndrome.[orpha.net]


  • Summary Epidemiology About 100 cases of this type have been reported in the literature to date. Clinical description The clinical signs are generally milder in dominant cases of RS than in the AR form.[orpha.net]
  • Summary Epidemiology Exact prevalence is unknown. About 200 cases have been reported to date. Cases have been reported primarily from the USA, Arab countries, Turkey, Czech Republic and Slovakia, the Indian subcontinent, and Brazil.[orpha.net]
  • In this case report, we presented the first report of Robinow syndrome in Iranian population, in order to improve the science and epidemiology related to this disease.[thritajournal.com]
  • Relevant External Links for WNT5A Genetic Association Database (GAD) WNT5A Human Genome Epidemiology (HuGE) Navigator WNT5A Atlas of Genetics and Cytogenetics in Oncology and Haematology: WNT5A No data available for Genatlas for WNT5A Gene Molecular cloning[genecards.org]
Sex distribution
Age distribution


  • Pathophysiology The most prominent and consistent features of van der Woude syndrome are orofacial anomalies caused by an abnormal fusion of the palate and lips at 30-50 days postconception.[emedicine.medscape.com]


  • Prevention Prevention of the disease is to determine the likelihood of having a child with this anomaly. To do this, conducted a survey of both parents, as well as installed instances of the disease in relatives.[health-and-beaty.blogspot.com]
  • Robinow Syndrome Prevention It is not possible to prevent the genetic disorder in advance as the factors that trigger the gene mutations are not known.[hxbenefit.com]
  • Transplantation Substance Use and Addiction Surgery Surgical Innovation Surgical Pearls Teachable Moment Technology and Finance The Rational Clinical Examination Tobacco and e-Cigarettes Toxicology Trauma and Injury Treatment Adherence United States Preventive[doi.org]
  • Robinow syndrome and fusion of primary teeth Department of Pediatric and Preventive Dentistry, Nair Hospital Dental College, Mumbai, Maharashtra, India Date of Web Publication 14-Sep-2017 Correspondence Address : Priti Sushil Jain Department of Pediatric[contempclindent.org]



  1. Afzal AR, Jeffery S. One gene, two phenotypes: ROR2 mutations in autosomal recessive Robinow syndrome and autosomal dominant brachydactyly type B.Hum Mutat. 2003;22(1):1-11.
  2. Mishra S, Agarwalla SK, Pradhan S. Robinow Syndrome: A Rare Diagnosis. J Clin Diagn Res. 2015;9(12):SD04-SD05.
  3. Patton M, Afzal A. Robinow syndrome. J Med Genet. 2002;39(5):305-310.
  4. Tamhankar PM, Vasudevan L, Kondurkar S, et al. Identification of Novel ROR2 Gene Mutations in Indian Children with Robinow Syndrome. J Clin Res Pediatr Endocrinol. 2014;6(2):79-83.
  5. Bacino C. ROR2-Related Robinow Syndrome. 2005 Jul 28 [Updated 2011 Aug 25]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.
  6. Person AD, Beiraghi S, Sieben CM, et al. WNT5A Mutations in Patients with Autosomal Dominant Robinow Syndrome. Dev Dyn. 2010;239(1):327-337.

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Last updated: 2019-07-11 21:42