MLS is an inherited disease affecting dogs of Beagle breed. It affects development and structure of connective tissues and manifests itself by extensive skin and joint fibrosis and affects even heart. MLS is caused by mutation in seventh exon of ADAMTSL2 gene (c.660C>T) for the fibrillin-1 protein which forms the main part of the tissue microfibriles. Single-point substitution results in defect in the protein reading frame and substitution of arginine for cysteine in codon 221, which has fatal impact on its function.
MLS manifests itself by quite specific characteristics. It is often quite easy to identify puppy affected with this syndrome within two or four weeks after birth. Beagles affected with MLS have shorter outer toes and they walk upright on their front feet (in what resembles a ballerina stance). Compared with healthy dogs, the affected beagles often have tighter skin, tight tendons and muscles. They often appear very well muscled. Their head shape is also notably different having a flat skull, higher ear set and slanted narrow eyes. The tails are often carried in a straight, stiff fashion and some have noticeable kinks in the tail. Dogs affected with MLS can be extremely cheerful and have an unusual temperament. The syndrome gets worse progressively in the first year of life and then the condition stabilizes.
The disease is inherited as a recessive trait. Dogs that have two copies of the mutant gene are affected with MLS, though the typical signs may be present to a various degree. Dogs carrying one copy of the mutant gene have no external symptoms affecting their health.
If two heterozygous dogs are mated, 25% of the offspring in the litter are expected to be healthy, 50 % of the offspring are expected to be carriers and 25 % of the offspring inherit the mutant allele from both parents and are expected to have MLS. The molecular-genetic test enables to identify the presence or absence of the mutation and determine a potential carrier of the disease.