Musladin-Lueke Syndrome

Musladin-Lueke syndrome is a genetic disease present in dogs of the Beagle breed. This condition is caused by mutations in the ADAMTSL2 gene that adversely affect the development and structure of the connective tissue and skin.

Symptoms

Affected dogs suffer from various clinical signs including a smaller body size and a peculiar gait, where they stand on their toes rather than on the pad of the foot. In addition, physical features such as a flattened head, stiff and tightly packed coat, and oblique, wide-spaced eyes may be noted. The severity of symptoms is highly variable, ranging from dogs with mild to moderate symptoms to severely affected dogs.

Disease Management

To date, Musladin-Lueke syndrome has no cure, but proper veterinary care and environmental adaptation can help improve the dog's quality of life.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

The disease was originally called "Chinese Beagle syndrome" and subsequently renamed after two prominent breeders of Beagles, Musladin and Lueke. Musladin-Lueke syndrome was first detected in Beagles in the 1970s and an incidence of 2-3% was estimated in the British and Australian subpopulations. Subsequently, through mapping and sequencing of likely candidate genes, Bader et al. (2010) identified the causative c.661C>T mutation in the ADAMTSL2 gene. The mutation causes a nonsynonymous change involving the substitution of an arginine for a cysteine in a highly conserved region of the protein. Therefore, this change probably affects the structure and function of the protein, which is part of the extracellular matrix and helps in the organization and stability of connective tissues, including skin, cartilage and blood vessels.

Most affected breeds

Beagle

Bibliography

Bader HL, Ruhe AL, Wang LW,et al. An ADAMTSL2 founder mutation causes Musladin-Lueke Syndrome, a heritable disorder of beagle dogs, featuring stiff skin and joint contractures. PLoS One. 2010 Sep 17;5(9):e12817.