Recurrent inflammatory pulmonary disease described in the Collie (Rough Collie), with an autosomal recessive hereditary basis. It is due to a frameshift variant in AKNA, a transcription factor involved in regulating inflammatory responses. The clinical picture resembles primary ciliary dyskinesia, with chronic pulmonary inflammation and recurrent pneumonia.

Described only in the Collie (Rough Collie). Among 88 genotyped dogs: 3 affected homozygotes, 67 clear and 18 heterozygotes (~20% carriers in that sample, which included relatives of the cases). There are no broad population frequencies (limited data).

- Chronic cough\n- Dyspnoea and exercise intolerance\n- Recurrent pneumonia and pulmonary infiltrates\n- Incomplete response to conventional antibiotic treatment\n- Loss of body condition and lethargy\n- Signs compatible with primary ciliary dyskinesia, whose known variants were ruled out

Hug et al. (2019) investigated three related Rough Collies with recurrent inflammatory pulmonary disease and signs similar to primary ciliary dyskinesia, without known PCD variants. Pedigree analysis suggested recessive inheritance and, by combined mapping and sequencing, they identified a 4-bp deletion in AKNA as the only private homozygous variant in the critical regions. Genotyping of 88 Rough Collies showed perfect agreement between genotype and phenotype.

- A genetic test is available for AKNA c.2717_2720delACAG.\n- Do not mate two carriers (25% affected homozygotes).\n- Mate carriers with clear dogs and retain only clear offspring for breeding.\n- Exclude affected animals from breeding.\n- Communicate the genetic status to breed breeders, given the low known frequency.

Differential diagnosis with primary ciliary dyskinesia, chronic bacterial pneumonia, allergic respiratory disease and idiopathic pulmonary fibrosis. The AKNA variant was identified in a single family, so the association, although very robust (perfect agreement and comparative functional data in the Akna-/- mouse, with neonatal death from systemic inflammation), is based on few cases and should be confirmed in larger series. The test makes it possible to avoid affected litters.

1. Hug P et al. 2019. AKNA Frameshift Variant in Three Dogs with Recurrent Inflammatory Pulmonary Disease. Genes. PMID: 31357536
2. OMIA:002205-9615. Recurrent inflammatory pulmonary disease in Canis lupus familiaris. Online Mendelian Inheritance in Animals.