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) . Symptoms may begin soon after birth, and the condition affects both genders equally . 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  . 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    . 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 . 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  .
Entire Body System
Short Stature in Children
Most children with Robinow syndrome experience growth delays after birth, resulting in slight to moderate short stature. [rarediseases.org]
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]
Jaw & Teeth
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 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]
(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]
The resulting dwarfism is associated with shortened and deformed limbs, brachydactyly, a short tail, costovertebral segmentation defects, maxillary and mandibular hypoplasia/malformations (cleft palate), and congenital heart anomalies (ventricular septal [doi.org]
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]
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  . 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  . 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  .
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- 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.
- 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.
- Person AD, Beiraghi S, Sieben CM, et al. WNT5A Mutations in Patients with Autosomal Dominant Robinow Syndrome. Dev Dyn. 2010;239(1):327-337.