Deafness in Dogs

George M. StrainLouisiana State UniversityBaton Rouge, Louisiana USA

Causes, Prevalence, andCurrent Research

Forms of Deafness inherited or acquired

congenital or later-onset

sensorineural or conductive

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

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

Definitions

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) 30% white Bull Terrier (n=346) 20% English Setter (n=3,656) 8% Australian Cattle Dog (n=296) 15% English Cocker Spaniel (n=1,136) 7% Jack Russell Terrier (n=56) 16%* Catahoula Leopard Dog (n=78) 63%*

Hearing Testing behavioral testing - sound stimuli outside of the animal's visual field

cannot detect unilateral deafnessanimals quickly adapt to testingdetected through other sensory modalities

electrodiagnostic testing - brainstem auditory evoked response (BAER)

objective, non-invasivedetects unilateral deafnesslimited 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

0

10

20

30

40

50

60

70

80

Bilateral Unilateral Deaf

Per

cen

t

N=5,33370.1% (3,740)

21.9% (1,167)

8.0% (426)

Prevalence of Deafness In Dalmatians By Country

United States 30% (G Strain, N=5,333))

United Kingdom 21% (M Greening, N=2,282)

Holland 18% (B Schaareman, N=1,208)

Effect of Parent Hearing Status On Deafness Prevalence

0

10

20

30

40

50

60

70

80

Bi Uni Deaf Bi Uni Deaf

Per

cen

t

B-B Parents (N=2,320) B-U Parents (N=728)

73%

21%

6%

59%

31%

11%

Effect of Sex On Deafness Prevalence

0

10

20

30

40

50

60

70

80

Bi Uni Deaf Bi Uni Deaf

Per

cen

t

Male (N=2,459)

71%

22%

7%

69%

22%

9%

Female (N=2,424)

Coat Pigmentation Genes In The Dalmatian

Base coat - underlying coat colorB - 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

0

10

20

30

40

50

60

70

80

90

100

Bi Uni Deaf Bi Uni Deaf

Per

cen

t

Patched (N=436) Not Patched (N=4,404)

90%

8%2%

68%

23%

9%

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

0

10

20

30

40

50

60

70

80

Bi Uni Deaf Bi Uni Deaf Bi Uni Deaf

Per

cen

t

BR-BR (N=4,246) BR-BL (N=372)

73%

21%

7%

49%

33%

18%

BL-BL (N=143)

50%

33%

17%

Effect of Retinal Pigmentation On Deafness Prevalence

0

10

20

30

40

50

60

70

80

Bi Uni Deaf Bi Uni Deaf

Per

cen

t

Pigmented (N=2,611)

71%

22%

7%

56%

29%

15%

Not Pigmented (N=623)

Impact Of Breed Standards

United States: allows blue eyes

Canada: does not allow blue eyes

Europe: does not allow blue eyes

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 melanocytes)

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 follow Mendelian genetics

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

strain@lsu.edu