Robinow-like syndrome (DVL2)

LABOKLIN Service ID: 8747

Genetic variants of the Dishevelled 1 (DVL1) and 3 (DVL3) genes cause the so-called Robinow syndrome in humans, which can be characterized by distinctive facial features (prominent forehead, widely spaced eyes, flat nasal bridge) as well as mesomelic limb shortening and cardiac, oral and urogenital anomalies.

In English Bulldogs, French Bulldogs and Boston Terriers, a variant of the DVL2 gene has been found to be fixed. The genetic variant results in an altered protein that affects an important cell-cell communication system crucial for tissue development.
The typical phenotype of these breeds includes a wide head, a short muzzle (brachycephaly), widely spaced eyes and a small size. Malformed, fused or lacking caudal vertebrae result in truncated and kinked tails, so that the breeds are also called screw tail breeds. In the three breeds, the DVL2 variant has been found to segregate with the breed defining phenotype as well as thoracic and caudal vertebral malformations in a recessive manner. Regarding to the thoracic vertebral malformations, the variant seems to have an incomplete and variable penetrance between different breeds. Moreover, the DVL2 variant contributes to the brachycephalic phenotype, in addition to other known genetic variants of the SMCO2 and BMP3 gene. The DVL2 variant could also be linked to other health concerns like the brachycephalic obstructive airway syndrome (BOAS) and congenital heart defects, but this is still part of ongoing research.

Besides to the screw tail breeds, the DVL2 variant has also been found homo- or heterozygous in the breeds Pit bull, Staffordshire Bull Terrier, Shih Tzu, American Staffordshire Terrier, Dogues de Bordeaux, Old English Bulldog and American Bulldog. In these breeds, the DVL2 variant seems to be associated with a brachycephalic phenotype and caudal vertebral malformations as well. However, in contrast to the screw tail breeds, the total number of the vertebrae is not reduced and the tail is not completely malformed. Furthermore, no thoracic vertebral malformations have been observed, perhaps due to the variable penetrance of this trait.

Method	sequencing
Breed list	American Bulldog, American Pitbull Terrier, American Staffordshire Terrier, Boston Terrier, Continental Bulldog, Dogue de Bordeaux, English Bulldog, French Bulldog, Olde English Bulldogge, Shih Tzu, Staffordshire Bull Terrier
Heredity	autosomal recessive with variable penetrance
Duration	1 - 2 weeks after arrival of the sample in the lab