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 Finger

  […] stature (dwarfism) - Short lower arms (mesomelic brachymelia - Small hands with clindodactyly and brachymesophalangy or achydactyly - of fifth finger (short fingers) - Small feet - Vertebral segmentation defects - Multiple rib anomalies - Hemivertebrae [ibis-birthdefects.org]

  Ramakrishnan Medicine Indian pediatrics 1988 Skeletal abnormalities including shortening of the long bones in the arms and legs, particularly the forearms; abnormally short fingers and toes; wedge-shaped spinal bones leading to an abnormal curvature of [semanticscholar.org]

  The first type is Autosomal recessive Robinow syndrome which is characterized by skeletal abnormalties including the shortening of the long bones in the arms and legs, particularly in the forearms; abnormally short fingers and toes; wedge-shaped spin [rarediseases411.blogspot.com]

  Both autosomal recessive and autosomal dominant inheritance have been described Autosomal recessive Robinow syndrome is more severe and is characterized by shortening of the long bones in the arms and legs; short fingers and toes; wedge-shaped spinal [dnatesting.uchicago.edu]

  Skeletal features may include shortening of the long bones in the arms and legs, short fingers and toes (brachydactyly), abnormal development of the spinal bones (hemivertebrae) that can cause an abnormal curve in the spine (kyphoscoliosis), abnormal [diseaseinfosearch.org]

• Dysmorphic Face

  The dysmorphic face was characterized by low set ears, flat-saddle nose, hypertelorism, elevated tip of nose and fish mouth (Figure 1). He also had brachydactily and a micropenis (Figure 2). Figure 1. [thritajournal.com]

  The dysmorphic face was characterized by low set ears, flat-saddle nose, hypertelorism, elevated tip of nose and fish mouth (Figure 1). He also had brachydactily and a micropenis (Figure 2). [brieflands.com]

• Short Stature in Children

  Most children with Robinow syndrome experience growth delays after birth, resulting in slight to moderate short stature. [rarediseases.org]

• Trisomy 21

  The incidence of trisomy 21 is 1 in 700 newborns. [rrnursingschool.biz]

• Swelling

  This 2-month-old infant with Caffey's syndrome (infantile cortical hyperostosis) shows the characteristic swelling of the jaw and right forearm. It usually occurs in a well-nourished infant. [americorpshealth.biz]

• Nausea

  The patient is followed up dentally since he was a baby and the following oral characteristics were present: malocclusion, deep palate, crowding, unilateral posterior crossbite, gingival hyperplasia, difficulty in cleaning, nausea during the dental approach [journalijdr.com]

• Brachydactyly

  Note characteristic fetal face (A), hypogenitalism (B) and brachydactyly of hands and feet (C, D). (Limb Malformations & Skeletal Dysplasia Clinic, MSU, NRC). Date 2008 Source Samia A Temtamy, Mona S Aglan. Brachydactyly. [commons.wikimedia.org]

  Type B1 brachydactyly is inherited as an autosomal dominant condition. [preventiongenetics.com]

  […] action=getRecordDetail&idt=808690 Other title Brachydactyly type B and Robinow syndrome : mutations of a single gene associated with two distinct phenotypes (en) Author GILGENKRANTZ, Simone Source MS. [pascal-francis.inist.fr]

• Decrease in Height

  […] length of neck 0000470 Short nose Decreased length of nose Shortened nose [ more ] 0003196 Short stature Decreased body height Small stature [ more ] 0004322 Small hand Disproportionately small hands 0200055 Thin upper lip vermilion Thin upper lip 0000219 [rarediseases.info.nih.gov]

• Hearing Impairment

  Conductive hearing impairment with temporal bone hyperostosis is the latest finding in RS that was described by Dion F. Ejukenboom. Therefore, the hearing of this reported case should be assessed. [thritajournal.com]

  It is characterized by growth and developmental delay, vision and hearing impairment, and impairment of the peripheral nervous system function. [icd10data.com]

• Hypertelorism

  The daughter had short stature, macrocephaly, hypertelorism, hepatosplenomegaly, short forearms and marked vertebral anomalies. [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]

  (B) The 3D reconstruction shows an upper lip with a characteristic eversion, hypertelorism, and a wide nasal root. [onlinelibrary.wiley.com]

  —Robinow's (fetal face) syndrome is a form of mesomelic dwarfism characterized by hypoplastic genitalia; atypical facies, with a flat profile, prominent forehead, hypoplastic mandible, hypertelorism, long philtrum, and short, flat upturned nose; and an [jamanetwork.com]

• Frontal Bossing

  The first case, second living child of the family, has all of the cardinal features of this syndrome including short stature, mesomelic shortening of forearms, frontal bossing, hypertelorism, anteverted nares, triangular mouth, hypoplastic genitalia and [ncbi.nlm.nih.gov]

  In this figure of the same infant note the marked frontal bossing, the large anterior fontanelle, the short nose, long philtrum, and micrognathia. 3.39 Figure 3.39. [rrnursingschool.biz]

• Large Anterior Fontanels

  In this figure of the same infant note the marked frontal bossing, the large anterior fontanelle, the short nose, long philtrum, and micrognathia. 3.39 Figure 3.39. [rrnursingschool.biz]

  —A 9-month-old black female infant with a negative family history and bilateral epiphora since birth had macrocrania, a large anterior fontanelle, frontal bossing, hypertelorism, a small mouth, a flat facial profile, a long philtrum (Fig 1), hyperplastic [jamanetwork.com]

  We experienced a boy diagnosed as a Robinow syndrome with fetal face(frontal bossing, hypertelorism, small up-turned nose, triangular mouth with down turned angles, micrognathia), large anterior fontanelle, cranium bifidum, mesomelic shortening, cryptorchidism [koreamed.org]

  Features can also involve head and neck (large anterior fontanel, posteriorly rotated ears, absent uvula, crowded teeth, prominent eyes), heart (right ventricular outlet obstruction), genitourinary (renal duplication, hydronephrosis, small penis, small [accessanesthesiology.mhmedical.com]

• Cryptorchidism

  We experienced a boy diagnosed as a Robinow syndrome with fetal face(frontal bossing, hypertelorism, small up-turned nose, triangular mouth with down turned angles, micrognathia), large anterior fontanelle, cranium bifidum, mesomelic shortening, cryptorchidism [koreamed.org]

  […] fifth finger Cone-shaped epiphysis Congenital fused vertebrae Congenital heart disease Congenital macrocephaly Congenital narrow spinal canal Congenital renal or ureteral anomaly Congenital vertebral abnormality Congenital widespread osteosclerosis Cryptorchidism [gamuts.net]

  […] manifest in the hands and feet as clinodactyly or brachydactyly ... spinal malformations, notably a tethered cord ... urinary incontinence ... lower extremity hypotonia ... scoliosis and vertebral fusion ... hypoplastic labia majora and clitoris ... cryptorchidism [ibis-birthdefects.org]

  including: mesomelic limb shortening: mesomelia hemivertebrae characteristic facies anomalies fetal facies hypertelorism 3 frontal bossing 3 long philtrum 3 hypogenitalism micropenis in males hypoplasia of the clitoris and labia minora in females. cryptorchidism [radiopaedia.org]

  […] 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 [symptoma.com]

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].

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]

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]

Specialized treatment often requires many families to travel in order to recieve care by specialist that have experience with this rare condition. [gofundme.com]

There are two main types of clinical studies: Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments. [rarediseases.info.nih.gov]

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]

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]

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 ... OMIM number ... ________________________________________________________________________________________________ Last Updated: 2009/03/09 ________________________________________________________________________________________________ [ibis-birthdefects.org]

The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome. [escholarship.org]

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]

Patient Epidemiology Analysis Robinow syndrome market also provides you with detailed market analysis for patient analysis, prognosis and cures. [databridgemarketresearch.com]

The discussion covers the phenotype spectrum, epidemiology, mode of inheritance, pathogenesis, and clinical profile of each condition, all of which is accompanied by a wealth of illustrations. [books.google.com]

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]

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]

Prevention How can I prevent Robinow syndrome? Unless couples undergo preimplantation genetic testing, there’s no way to prevent the mutation that leads to Robinow syndrome. [my.clevelandclinic.org]

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]

In response to increased HH signaling, the Prickle1Bj/Bj cranial base growth plates undergo precocious maturation which prevents its proximal-distal expansion resulting in the wider midface, and shorter stature. [d-scholarship.pitt.edu]

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.