Burmese Head Defect (BHD)

 

Gene: ALX1

Transmission: Autosomal, co-dominant

Animals with one copy of the mutation (carrier animals) will have the head defect phenotype.  Animals with two copies of the mutation will display a severe phenotype that is not compatible with life.  A carrier animal, mated to a normal animal, will pass on the mutation to 50% of its progeny.

Mutation: Deletion, ALX1 gene; c.496-508 delCTCTCAGGACTG, p.(A166_T169 deletion), feline chromosome B4.

Breed: American Shorthair, Bombay, Burmese

Medical system: skeletal

Age of onset of symptoms: at birth

The craniofacial anomalies of the Burmese is a form of brachycephaly named “contemporary Burmese” but also called “Burmese Head Defect” (BHD) or frontonasal dysplasia (DFN).  A male Burmese cat with brachycephaly phenotype from a natural mutation was observed in the United States in the late 1970’s to become a popular sire.  More recently a mutation in the ALX1 gene has been identified as the cause of the brachycephaly phenotype when present in one copy.  When the mutation is present in two copies (homozygous mutated), a severe craniofacial defect is observed that is not compatible with life.  Now anomalies include agenesis (absence) of the structures deriving from the median nasal prominence (upper lip and nose), duplication of the maxillary process, and duplication of the vibrissae and canines and spina bifida.

 

References:

OMIA link: [1551-9685]

Berteselli GV, Palestrini C, Scarpazza F, et al. (2023) Flat-faced or non-flat-faced cats? That is the question. Animals (Basel) 13:206. [pubmed/36670746]

Gündemir O, Szara T, Yalin EE, et al. (2023) Examination of shape variation of the skull in British Shorthair, Scottish Fold, and Van cats. Animals (Basel) 13:614.  [pubmed/36830403]

Anderson H, Davison S, Lytle KM, et al. (2022) Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats.  PLoS Genet. 16;18(6):e1009804.  [pubmed/35709088]

Geiger M, Schoenebeck JJ, Schneider RA, et al. (2021) Exceptional Changes in Skeletal Anatomy under Domestication: The Case of Brachycephaly. Integr Org Biol. 3(1). [pubmed/34409262]

Lyons LA, Erdman CA, Grahn RA, et al. (2016) Aristaless-like homeobox protein 1 (ALX1) variant associated with craniofacial structure and frontonasal dysplasia in Burmese cats. Dev Biol. 409(2):451–458. [pubmed/26610632]

Noden DM, Evans HE. (1986) Inherited homeotic midfacial malformations in Burmese cats. J Craniofac Genet Dev Biol Suppl. 1986;2:249–266. [pubmed/2878018]

 

Contributed by: Remi Bissonette and Tamayo Matéo Lebel, Class of 2027, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS).