Deafness: hereditary

Etiology

• Two genes for pigmentation are linked to hereditary deafness in dogs.
• The first is the merle (M) locus, controlled by the premelanosome protein (PMEL) gene, previously called silver (SILV).
• Merle is broadly characterized by the alleles ‘M’ and ‘m’, where m represents the wildtype allele for normal pigmentation and ‘M’ indicates the presence of the Merle variant in any form.
• Merle coat colour has been associated with hearing loss in several breeds, proposedly owing to the non-survival or degeneration of melanocytes within the cochlear of the inner ear.
• The dominant M allele is carried by many breeds, including (but not restricted to) the Border Collie, Australian Shepherd, Old English Sheepdog, Dalmatian, Great Dane and the Cardigan Welsh Corgi, and is associated with an increased risk of deafness.
• Neither heterozygosity or homozygosity for the M allele (Mm and MM respectively) invariably results in deafness, although the risk increases with the number of M alleles carried.
• The second gene is MITF (micropthalmia-associated transcription factor) with MITF-associated white markings linked to increased prevalence of pigment-associated congenital sensorineural deafness.
• The white spotting alleles of MITF (Piebald, sᵖ) , and Extreme White (sʷ), common in breeds such as the Dalmatian, Bull Terrier and Beagle, have also been associated with higher risk deafness.
• The inheritance of pigment-associated deafness is complex and the mechanism by which it occurs is not incompletely understood.

Forms of deafness not associated with pigment

• Early Adult Onset Deafness in Border Collies is not associated with pigment and has been associated with a region on canine chromosome 6, although precise causal variants have not been published to date.
• A non-syndromic form deafness in Beauceron dogs Beauceron is characterized by a bilateral hearing loss in puppies and is also not linked to coat color.
• Rhodesian Ridgebacks can suffer from progressive hearing loss within 1-2 years after birth, that is not associated with pigment and dog is associated with an in-frame deletion in the EPS8L2 gene.
• A form of congenital deafness has been described in the Australian Stumpy Tail Cattle that is associated with A missense mutation in the KLF7 Gene.
• Bilateral deafness with concurrent vestibular dysfunction has been described in the Doberman pinscher is associated with a coding mutation in the MYO7A gene.

Predisposing factors

General

• Genotype of parents.
• Genotype of offspring.

• Breed.

Pathophysiology

• Neonatal puppies → absence of melanocytes (function unknown) in stria vascularis of cochlea → degeneration of stria vascularis → degeneration of hair cells of cochlear ducts → sensorineural deafness.
• Dobermans → direct loss of cochlear hair cells → deafness with vestibular signs. Simple autosomal recessive.

Timecourse

• Degeneration of inner ear structures completed by 5 weeks old.
• For early adult onset forms of deafness (eg Border Collie and Rhodesian Ridgeback) dogs are born with normal hearing that degenerates later in life.