Brachydactyly type B (BDB) is an autosomal recessive skeletal disorder characterized by the absence or underdevelopment of terminal phalanges. Typical features of the condition include hypoplasia or aplasia of distal phalanges and nails, short middle phalanges, and deformed thumbs and big toes. The condition shows wide-ranging phenotypic variability ranging from a mild version characterized by slightly shortened distal phalanges and nails, and frequent distal symphalangism, to severe forms characterized by amputation-like phenotype with absence of distal phalanges and/or nails of fingers. The most severe form of BDB includes severe skeletal defects primarily affecting the distal limbs and the spine and resembles the clinical features of Robinow Syndrome. Interestingly, both Robinow Syndrome and BDB are caused due to defects in the same gene.
Loss of function mutations in the ROR2 (Receptor Tyrosine Kinase Like Orphan Receptor 2) gene are responsible for the phenotypic effects of BDB. Although it is known that the ROR2 protein is involved in protein-protein interactions, its exact function and its role in the development of BDB is not known. It is speculated that the protein may be involved in the formation of chondrocytes, and thus play a role in cartilage and growth plate development. Furthermore, studies have been performed on the genotype-phenotype correlations of ROR2 and BDB, and it has been shown that distal mutations on the gene tend to cause more severe phenotypes.