Acute Respiratory Distress Syndrome, ARDS

Gene: ANLN

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, ANLN gene; c.31 C>T, p.(R11 STOP)

Medical system: Respiratory

Breeds: American Staffordshire Terrier/Amstaff, Bernese Mountain Dog, Bloodhound, German Shepherd, Golden Retriever

Age of onset of symptoms: Between 5 and 10 months in puppies, sometimes between 6 and 8 years in adults.

Acute respiratory distress syndrome is a condition resulting from inflammation of the lungs.  In Dalmatians a hereditary form of acute respiratory distress syndrome is reported due to a mutation in the ANLN gene, whereby there is a congenital default in lung repair mechanisms.  At the onset of clinical symptoms, the animal will present with tachypnea (increased breathing rate) and dyspnea (breathing that seems laboured). These breathing variations may be accompanied by vomiting or regurgitation.  As symptoms progresses over a period of one to six weeks, the affected animal will show bluish discoloration (cyanosis) of skin and mucous membranes.  The disease may progress to pulmonary edema, and may cause traumatic lesions near the lungs, such as pneumomediastinum or herniation of the esophageal hiatus of the diaphragm.  The affected animal will die in acute respiratory distress or, more often than not, be euthanized for humanitarian reasons.  On autopsy, affected puppies sometimes will be missing a kidney, suggesting a developmental syndrome associated with this mutation.  In a recent survey of genetic disease mutations, Donner et al. (2023) reported no evidence of the ANLN mutation in 820 Dalmatians sampled, although the mutation was detected in several other breeds.

References:

OMIA link: [2539-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Holopainen S, Hytönen MK, Syrjä P, et al. (2017) ANLN truncation causes a familial fatal acute respiratory distress syndrome in Dalmatian dogs. PLoS Genet 13:e1006625.  [pubmed/28222102]

Syrjä P, Saari S, Rajamäki M, et al. (2009) Pulmonary histopathology in Dalmatians with familial acute respiratory distress syndrome (ARDS). J Comp Pathol 141:254-9.  [pubmed/19628215]

Jarvinen AK, Saario E, Andresen E, et al. (1995) Lung injury leading to respiratory distress syndrome in young Dalmatian dogs Journal of Veterinary Internal Medicine 9:162-168. [pubmed/7674217]

Contributed by: Chloé Giard-Montpetit and Sabrina Girardin, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).