Deafness In Dogs: Causes, Prevalence, And Current Research

Deafness in Dogs Causes, Prevalence, and Current Research George M. Strain Louisiana State University Baton Rouge, Louisiana USA

Forms of Deafness ■

inherited or acquired

■

congenital or later-onset

■

sensorineural or conductive

■

Result: eight possible combinations (i.e., acquired later-onset sensorineural deafness)

Definitions ■

■

sensorineural deafness - loss of function because of loss of cochlear hair cells or cochlear nerve neurons conductive deafness - blockage of sound transmission through outer and/or middle ear without damage to cochlea

Inherited Congenital Sensorineural Deafness ■

usually associated with the genes responsible for white hair ➨piebald gene (sp) and extreme piebald (sw)

gene ➨merle (M) gene

deafness develops at 3-4 weeks of age after the blood supply to the cochlea (stria vascularis) degenerates ■ strial degeneration is thought to result from absence of pigment cells (melanocytes) ■ other pigmentation effects are frequently seen ■

Dog Breeds With Congenital Deafness reported in over 80 dog breeds ■ prevalence (unilateral and bilateral) worst in: ■

Dalmatian (n=5,333) ■ white Bull Terrier (n=346) ■ English Setter (n=3,656) ■ Australian Cattle Dog (n=296) ■ English Cocker Spaniel (n=1,136) ■ Jack Russell Terrier (n=56) ■ Catahoula Leopard Dog (n=78) ■

30% 20% 8% 15% 7% 16%* 63%*

Hearing Testing ■

behavioral testing - sound stimuli outside of the animal's visual field ➨cannot detect unilateral deafness ➨animals quickly adapt to testing ➨detected through other sensory modalities

■

electrodiagnostic testing - brainstem auditory evoked response (BAER) ➨objective, non-invasive ➨detects unilateral deafness ➨limited availability

Brainstem Auditory Evoked Response

Genetics of Congenital Deafness ■

■

Doberman - simple autosomal recessive pigment-associated deafness in dogs most likely polygenic, incomplete penetrance, or other mechanism – NOT simple autosomal recessive merle gene - dominant; homozygous dogs have additional health problems ■ piebald genes - recessive, but all dogs in the breed are homozygous ■

Demi Azure Pedigree

6 (5)

12 (11)

Dalmatian Deafness Prevalence in the US 80

N=5,333

70.1% (3,740)

70

Percent

60 50 40

21.9% (1,167)

30 20

8.0% (426)

10 0 Bilateral

Unilateral

Deaf

Prevalence of Deafness In Dalmatians By Country ■

United States

■

United Kingdom 21%

(M Greening, N=2,282)

■

Holland

(B Schaareman,

N=1,208)

30%

18%

(G Strain, N=5,333))

Effect of Parent Hearing Status On Deafness Prevalence 80 70

B-B Parents (N=2,320) 73%

59%

60 Percent

B-U Parents (N=728)

50 40

31%

30

21%

20

11%

6%

10 0 Bi

Uni

Deaf

Bi

Uni

Deaf

Effect of Sex On Deafness Prevalence 80 70

Male (N=2,459)

Female (N=2,424) 69%

71%

Percent

60 50 40 30

22%

22%

20

7%

10

9%

0 Bi

Uni

Deaf

Bi

Uni

Deaf

Coat Pigmentation Genes In The Dalmatian Base coat - underlying coat color ➨B - black (dominant) ➨b - liver (recessive) ■ Extreme piebald gene - sw - white covering, recessive but homozygous in all Dalmatians (hair is white if it contains no pigment granules [melanin] or other substances which absorb light) ■ Ticking gene - T - dominant, produces holes in white to show underlying coat color ■

Effect of the Extreme Piebald Gene ■

■

Weak gene expression: failure of the piebald gene to completely suppress the underlying coat color (black or liver) results in a patch Strong gene expression: suppresses pigmentation in the iris (blue eyes) and tapetum (red eye), and in the stria vascularis (deafness)

Effect of Patch On Deafness Prevalence 100 90

Not Patched (N=4,404)

Patched (N=436) 90%

80

68%

Percent

70 60 50 40

23%

30 20

8%

10 0 Bi

Uni

9%

2% Deaf

Bi

Uni

Deaf

Effect of Eye Color (Brown or Blue) On Deafness Prevalence 80 70

BR-BR (N=4,246)

BL-BL (N=143)

73%

60 Percent

BR-BL (N=372)

49%

50 40

50% 33%

33%

30

21%

20

18%

17%

7%

10 0 Bi

Uni

Deaf

Bi

Uni

Deaf

Bi

Uni

Deaf

Effect of Retinal Pigmentation On Deafness Prevalence 80 70

Pigmented (N=2,611) 71%

56%

60 Percent

Not Pigmented (N=623)

50 40

29%

30

22%

20

15%

7%

10 0 Bi

Uni

Deaf

Bi

Uni

Deaf

Impact Of Breed Standards ■

United States: allows blue eyes

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Canada: does not allow blue eyes

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Europe: does not allow blue eyes

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Efforts through breedings to reduce blue eyes in Norwegian Dalmatians also reduced deafness prevalence.

Breeding Recommendations best advice: don't breed affected animals ■ a unilaterally deaf animal is genetically the same as a bilaterally deaf animal, and SHOULD NOT BE BRED! ■ it is unwise to repeat breedings that produced large numbers of deaf animals ■ avoid breeding to animals with a history of producing many deaf offspring ■

Breeding Recommendations (cont.)

do not totally breed away from patches - possibly accept in the breed standard ■ avoid breedings to blue eyed animals ■

■

■

ALWAYS KNOW THE HEARING STATUS OF DOGS YOU BREED TO! BREEDING DECISIONS SHOULD ALWAYS TAKE INTO CONSIDERATION THE OVERALL GOOD OF THE BREED

Possible Impact of Selective Breeding ■

a recent study by Wood & Lakhani* suggested that selective breeding against unilaterally and bilaterally deaf animals could reduce deafness to below 15% and 4% respectively. *The Veterinary Journal 154:121, 1997

■

4-5 generations of selective breeding would probably be necessary for a detectable impact on overall prevalence.

Current Research

Study: Molecular Genetics of Deafness AKC/CHF: Murphy, Strain "Genetics of Hereditary Deafness in the Domestic Dog" ■ candidate genes ■

– mitf – c-kit

DNA collection from affected pedigrees – Dalmatian – English Cocker Spaniel – English Setter ■ determination of mode of inheritance ■

Study: Molecular Genetics of Deafness ■

mitf human homolog of the mouse microphthalmia (mi) gene ■ responsible for >20% of cases of Waardenburg Syndrome type 2 in humans ■ regulates the expression of several pigment genes ■ necessary for transition of precursor cells to melanoblasts (which become ■

Study: Molecular Genetics of Deafness ■

c-kit

tyrosine kinase receptor ■ activation of the c-kit receptor regulates mitf function ■ mutations result in the absence of melanocytes and functional mast cells, as well as defects in ova and sperm development and blood cell formation ■ gene defects in mice produce dominant white spotting and deafness ■ gene defects in humans produce piebaldism and occasionally deafness ■

Study: Molecular Genetics of Deafness

Results: mitf – not causative for deafness ■ c-kit – not causative for deafness ■ mode of inheritance: ■

NOT simple autosomal recessive ■ best modeled as being inherited as a single “locus” but one that does not ■

Other Ongoing Molecular Genetic Studies • AKC/CHF: Murphy, Strain: "Whole genome screens using microsatellite markers in genetic analyses of hereditary deafness in the Dalmatian and English Setter“ • pedigree of >200 Dalmatians with DNA • English setter pedigree being assembled • whole-genome screens underway • further funding being sought from NIH & CHF

References: Strain GM. Deafness in Dogs & Cats web page: www.lsu.edu/deafness/deaf.htm ■ Strain GM. 1996. Aetiology, prevalence and diagnosis of deafness in dogs and cats. British Veterinary Journal 152 (1): 17-36. ■ Little CC. 1957. The Inheritance Of Coat Color in Dogs. Howell Book House: New York. 194 pp. ■ Searle AG. 1968. Comparative Genetics of Coat Colour In Mammals. Logos Press/ Academic Press: London. 310 pp. ■

Deafness in Dogs & Cats Web Site: www.lsu.edu/deafness/deaf.htm [email protected]