X-Linked Tremors

X-linked tremors, trembling puppy syndrome or canine hypomyelination is an inherited defect that causes a delay in the myelination of the nervous system of springer spaniel dogs.

Symptoms

Symptoms usually appear shortly after birth, between the first and second week. Affected puppies begin to show severe generalized tremors. The most affected puppies may have trouble feeding because of their tremors and stunted growth. Episodes of tremors decrease when the puppy is less active. The life expectancy of puppies does not exceed 4 months of age.

Disease Management

Unfortunately, the disease has no cure, the symptoms are severe and progressive, which in most cases leads to euthanasia.

Genetic basis

This disease follows an X-linked recessive mode of inheritance. Recessive X-linked inheritance means that female dogs must receive two copies of the mutation or pathogenic variant (one from each parent) to develop the disease, whereas males need only one copy of the mutated gene or variant from the dam to develop the disease. Male dogs usually show symptoms of the disease. Each male puppy born to a mother carrying the mutation has a 50% chance of inheriting the mutation and thus the risk of developing the disease. Bitches that do not carry the mutation are not at increased risk of having affected puppies. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Myelin is a white substance that surrounds the axon of nerve cells and facilitates rapid transmission of the nerve impulse when muscles contract. Myelin enables fine muscle control and without it, precise muscle control is not possible. In the central nervous system, myelin is produced by cells called oligodendrocytes. It is thought that in X-linked tremor disease there is an alteration in the differentiation of oligodendrocytes and in the production of myelin by these cells. In dogs of the Springer Spaniel breed affected by the disease, the axons of the central nervous system are abnormally demyelinated and in those with myelin sheath, their thickness is minimal. The gene affected in this pathology is PLP1 which produces myelin proteolipid protein which is the most abundant protein in myelin and plays a crucial role in the formation and maintenance of the multilamellar structure of myelin. The mutation in PLP1 responsible for the disease in springer spaniel dogs is c.110A>C, identified by Nadon et al.

Most affected breeds

Springer Spaniel

Bibliography

Griffiths IR, Duncan ID, McCulloch M. Shaking pups: a disorder of central myelination in the spaniel dog. II. Ultrastructural observations on the white matter of the cervical spinal cord. J Neurocytol. 1981 Oct;10(5):847-58.

Nadon NL, Duncan ID, Hudson LD. A point mutation in the proteolipid protein gene of the 'shaking pup' interrupts oligodendrocyte development. Development. 1990 Oct;110(2):529-37.