Genetic basis of Frontonasal Dysplasia - also known as Burmese Head Defect, is caused by a 12 base pair in-frame deletion mutation in the ALX1 gene, specifically c.496_507delCTCTCAGGACTG. The ALX1 gene encodes a homeobox protein important for craniofacial development. This mutation is inherited in an autosomal co-dominant (semi-dominant) manner. Cats with one copy (heterozygous) show brachycephaly (a shortened facial structure) typical of the breed, while cats with two copies (homozygous) suffer from severe craniofacial malformations incompatible with life.
Pathophysiology - The ALX1 mutation disrupts normal development of the skull and facial features in the fetus. Homozygous affected kittens have severe malformations including duplication of structures like whisker pads and hard palate, incomplete skull closure, malformed or absent eyes and ears, and brain protrusion covered by skin. These defects arise due to failure of normal tissue development in the frontonasal region, leading to drastic craniofacial deformities.
Complications - Affected homozygous kittens may be stillborn or require euthanasia soon after birth, as the condition is incompatible with life. Those heterozygous for the mutation display the breed-desired brachycephalic facial shape but are carriers who risk producing affected offspring if mated with another carrier.
Why This Matters to Breeders and Vets - Since the mutation is co-dominantly inherited, breeders must avoid mating two carriers to prevent producing kittens with the lethal craniofacial defect. Genetic testing for the ALX1 mutation is recommended for breeding decisions to reduce the incidence of this severe congenital disorder. Vets should consider this diagnosis with typical clinical signs and advise breeders accordingly.
Summary - this is a severe congenital craniofacial malformation caused by a 12 bp deletion in the ALX1 gene inherited in an autosomal co-dominant manner. Homozygous kittens have life-incompatible frontonasal dysplasia, while heterozygous cats exhibit brachycephalic facial features characteristic of the Burmese breed. Genetic testing is important for effective breeding management to prevent affected kitten.