ROBINOW SYNDROME

Scientific Background

Robinow syndrome is a rare genetic syndrome, the main symptoms of which are characteristic craniofacial features (prominent forehead and flat midface, short nose with everted nasal floor, wide interocular distance), diminutive growth with mesomelic shortening especially of the upper extremities, brachydactyly-clinodactyly V and hypoplastic genitals, especially in males. Cognitive abilities are normal for 80 to 90% of cases. In 10 to 20% a developmental disorder is described.

The first report by Meinhard Robinow et al. (1969) of a family with affected persons in six generations suggested an autosomal dominant pattern of inheritance. Affected siblings with healthy parents, especially with consanguinity, showed that there is also an autosomal recessive inherited form. Pathogenic variants in the ROR2 gene (Afzal et al., Bokhoven et al.), which codes for a tyrosine kinase, were found to be the cause of this form; its pathogenic variants also cause an autosomal dominant form of brachydactyly type B. Person et al. (2010) found pathogenic variants in the WNT5A gene to be the genetic cause of the autosomal dominantly inherited form in the originally described family, and in 2015 pathogenic changes in the genes DVL1 and DVL3 were found to be a further cause (White et al.). Thus, three forms are genetically distinguished at this time. Clinically, the dominant forms are similar, while the recessive form seems to be associated with more pronounced short stature and additional skeletal malformations in the area of the ribs and vertebrae.

References

White et al. 2018, Am J Hum Genet 102:27 / White et al. 2016, AJHG, 98:553 / White et al. 2015, AJHG 96:645 / Person et al. 2010, Dev Dyn 239:327 / van Bokhoven et al. 2000, Nat Genet 25:423 / Afzal et al. 2000, Nat Genet 25:419 / Robinow et al. 1969, Am J Dis Child 117:645