Hereditary cataract associated with mutations in the HSF4 gene in three breeds: Staffordshire Bull Terrier, Boston Terrier and Australian Shepherd. It causes bilateral lens opacity, often of juvenile onset, progressing to blindness. The mutation behaves recessively in the Staffordshire Bull Terrier and Boston Terrier, and dominantly/co-dominantly in the Australian Shepherd. The variant is also documented in the French Bulldog (OMIA:001758; UK Kennel Club), although without a breed-specific peer-reviewed article.

The Staffordshire Bull Terrier, Boston Terrier and Australian Shepherd are among the breeds with early hereditary cataract. Carrier frequencies by country are not consolidated. The French Bulldog is documented for HSF4 (OMIA:001758; UK Kennel Club); without a breed-specific peer-reviewed article.

- Bilateral and symmetrical lens opacity
- Posterior nuclear or cortical cataract of juvenile onset
- Progressive reduction of vision leading to blindness
- White or bluish pupillary reflex
- No associated pain or ocular signs except complications

The genetic basis of canine hereditary cataract associated with HSF4 was characterized through the work of Mellersh's group in the mid-2000s. In 2006 a 1-bp insertion in HSF4 was identified in the Staffordshire Bull Terrier and Boston Terrier (recessive) and, in 2009, a 1-bp deletion at the same nucleotide in the Australian Shepherd (dominant). The late-onset cataract of the Boston Terrier is genetically distinct and is not associated with this mutation.

- Test breeding animals for the breed-specific variant
- In recessive breeds, do not breed two carriers together: 25 % of the litter would be affected
- In the Australian Shepherd, assess the risk of matings with heterozygotes (dominant/co-dominant expression)
- A carrier may be bred to a clear dog; test the offspring intended for breeding
- Complement with an annual ophthalmological examination to rule out cataracts not linked to HSF4
- Do not offer the test to breeds without published validation (e.g. French Bulldog)

Differential diagnosis with non-hereditary congenital cataracts, traumatic cataracts and those secondary to diabetes or uveitis. There are forms of cataract in these breeds not explained by the known HSF4 mutation, so a negative test does not guarantee the absence of cataract. In the Dachshund and the Entlebucher the mutation has not been associated with cataract (negative study). Phacoemulsification surgery is the treatment of choice in affected animals.

1. Mellersh CS, et al. Identification of mutations in HSF4 in dogs of three different breeds with hereditary cataracts. Vet Ophthalmol. 2006;9(5):369-378. PMID: 16939467
2. Mellersh CS, et al. Mutation in HSF4 associated with early but not late-onset hereditary cataract in the Boston Terrier. J Hered. 2007;98(5):531-533. PMID: 17611257
3. Mellersh CS, et al. Mutation in HSF4 is associated with hereditary cataract in the Australian Shepherd. Vet Ophthalmol. 2009;12(6):372-378. PMID: 19883468
4. Müller C, et al. Evaluation of canine heat shock transcription factor 4 (HSF4) as a candidate gene for primary cataracts in the Dachshund and the Entlebucher Mountain dog. Vet Ophthalmol. 2008;11(1):34-37. PMID: 18190350