Multi-disease genetic panel for the French Bulldog bringing together five molecular tests: hereditary cataract (HSF4), chondrodysplasia and chondrodystrophy with disc risk (CDPA & CDDY), cystinuria, congenital hypothyroidism with goitre (CHG) and degenerative myelopathy (DM exon 2). The conditions affect very different systems (ocular, musculoskeletal, urinary, endocrine and neurological), so the panel is a tool for the overall management of breeding. Molecular testing is complementary to —not a substitute for— ocular, orthopaedic and thyroid examination for breeding selection.

Applicable breed: French Bulldog. HSF4 documented in the breed (OMIA:001758); the remaining variants (CDDY/CDPA) are widely distributed. Reliable carrier frequencies in the Spanish breeding population are not systematically published (limited data).

- Bilateral lens opacity from puppyhood (HSF4)\n- Reduced vision and progressive blindness\n- Short legs, chondrodystrophic conformation (CDPA & CDDY)\n- High risk of disc herniation and spinal neurological signs (CDDY/IVDD risk)\n- Urolithiasis due to cystine stones with urinary obstruction (cystinuria)\n- Lethargy, failure to thrive, depigmented hair and goitre (CHG)\n- Progressive hindlimb paresis with ataxia (DM)\n- Multifocal retinal lesions with altered vision (CMR1)

The different tests were developed independently from the work of canine genetics groups. HSF4 cataract (insertion in HSF4, recessive) was described in the Staffordshire Bull Terrier, Boston Terrier and Australian Shepherd (Mellersh 2006); the same variant is also documented in the French Bulldog (OMIA:001758; UK Kennel Club), although without a breed-specific peer-reviewed article. Canine chondrodysplasia was linked to a retrogene insertion of FGF4 on chromosome 18 (CDPA), and a second FGF4 insertion on chromosome 12 associated with chondrodystrophy and risk of disc herniation (CDDY/IVDD risk) was subsequently described. Congenital hypothyroidism with goitre was associated with a thyroid peroxidase (TPO) defect in one case of French Bulldog (Major 2015); the population basis in the breed is limited. Canine DM was linked to the SOD1 exon 2 variant in 2009. Cystinuria in the French Bulldog has a sex-dependent presentation and its molecular genetics is not entirely settled in the accessible literature.

- Genotype breeding animals before mating; the panel covers six conditions in a single sample\n- For HSF4 (recessive): do not mate two carriers — 25% affected homozygotes; carrier×clear with testing. For CHG: the test exists but the basis in the breed is a single case; decide with phenotype + test, without alarm\n- For CDPA and CDDY (dominant): heterozygotes transmit the variant to 50% of the offspring; in breeds with a chondrodystrophic standard, consider not increasing the FGF4 dose to minimise the risk of disc herniation\n- For DM: do not breed with homozygotes; carriers × clear (late onset: the test alone does not decide in young animals)\n- For cystinuria (SLC3A1 haplotype): do not mate two carriers/homozygotes; with a high allele frequency, use the test as a guide for prophylaxis\n- After a confirmed clinical case, do not repeat the parental mating and communicate the status to the buyer

HSF4 cataract must be differentiated from non-genetic congenital cataracts (infectious, toxic) and from senile nuclear sclerosis. Annual ocular examination (ECVO/CERF) complements the HSF4 test. Assessment of CDDY/IVDD risk is interpreted together with conformation and weight management: the test does not predict the timing or location of the herniation. CHG must be differentiated from juvenile autoimmune hypothyroidism and from iodine deficiency. DM is a diagnosis of exclusion: rule out spinal cord compression before attributing the picture to SOD1.edular before attributing the picture to SOD1.

1. Mellersh et al. 2006, mutaciones HSF4 en catarata hereditaria canina (PMID 16939467)
2. Brown et al. 2017, retrogén FGF4 en CFA12: condrodistrofia y hernia discal (PMID 29073074)
3. Awano et al. 2009, SOD1 exón 2 y mielopatía degenerativa (PMID 19188595)
5. Major et al. 2015, disormonogénesis tiroidea (TPO) en un Bulldog francés (PMID 26478542)
6. Cistinuria en perro y gato: revisión 2021 (PMID 34438894)
7. Mellersh et al. 2007, HSF4 y catarata precoz (no tardía) en Boston terrier (PMID 17611257)