Lethal acrodermatitis (LAD) is a severe genetic disease of the Bull Terrier and the Miniature Bull Terrier, with autosomal recessive inheritance, caused by a splicing defect in the MKLN1 gene. It presents with erosive and scaling skin lesions on the limbs and muzzle, diarrhoea, pneumonia, growth retardation and immunodeficiency (with decreased IgA), and is usually lethal before two years of age.

Described in the Bull Terrier and the Miniature Bull Terrier. No reliable population carrier frequencies are available; the variant has not been found in other breeds analysed.

- Erythematous, scaling and erosive or ulcerated skin lesions with crusts on the feet, distal limbs, elbows, hocks and muzzle
- Hyperkeratosis of the footpads and nail deformity
- Abnormally arched hard palate, often impacted with food debris
- Diarrhoea
- Pneumonia and other recurrent infections
- Decreased IgA and immunodeficiency
- Growth and developmental retardation
- Hair-coat dilution in pigmented areas
- Death or euthanasia before two years of age

Described clinically in the Bull Terrier decades ago, its molecular basis was identified in 2018: Bauer et al. found by whole-genome sequencing an intronic variant in MKLN1 that alters splicing and causes skipping of exon 4 with a reading-frame shift. The variant showed perfect association in a combined cohort of Bull Terriers and Miniature Bull Terriers (46 cases and 294 controls) and was absent in 462 dogs of 62 other breeds.

- Genotype Bull Terrier and Miniature Bull Terrier breeding animals
- Do not mate two carriers: 25 % risk of affected puppies
- A carrier may be mated with a clear animal; test the offspring intended for breeding
- Exclude affected homozygotes from breeding
- Confirm the status before any mating, since carriers are healthy

The differential diagnosis includes other canine dermatopathies and immunodeficiencies. The combination of acral lesions, arched palate, diarrhoea and recurrent infections in a young Bull Terrier is highly suggestive. Confirmation is molecular (MKLN1). It is important not to confuse this entity with other acrodermatitides or with simple colour dilution.

1. Bauer A et al. 2018. MKLN1 splicing defect in dogs with lethal acrodermatitis. PLoS Genet. PMID: 29565995
OMIA002146-9615.