Hereditary frontonasal dysplasia of the Burmese cat, caused by a 12-bp in-frame deletion in ALX1. The allele is co-dominant: heterozygotes show the brachycephalic 'Contemporary Burmese' phenotype, whereas homozygotes suffer a severe craniofacial defect (agenesis of derivatives of the medial nasal prominence, meningoencephalocele and ocular degeneration) incompatible with life.

Documented in the Burmese cat ('Contemporary Burmese' line). The variant was not found in cats unrelated to that line. Broad population frequencies are not available (limited data).

- Marked brachycephaly in heterozygotes (breed trait)\n- In homozygotes: agenesis of derivatives of the medial nasal prominence\n- Lateral duplication of derivatives of the maxillary process (canines and vibrissal fields)\n- Telencephalic meningoencephalocele\n- Secondary ocular degeneration\n- Condition incompatible with life; affected kittens usually require euthanasia

Lyons et al. (2016) studied the craniofacial defect of the Contemporary Burmese for about 20 years, linked to a very popular stud from the late 1970s. Using linkage analysis, homozygosity mapping and GWAS they localised the trait to chromosome B4 and a 12-bp deletion in ALX1, present in 100 % of affected cats. The trait had previously been described as brachycephaly; OMIA created a specific entry because it is lethal in homozygosity.

- A genetic test is available for ALX1 c.497_508del.\n- Do not mate two heterozygotes: 25 % of the offspring would be homozygous and lethal.\n- Bear in mind that the allele is the trait of the Contemporary line, so selection depends on the degree of brachycephaly desired.\n- Pairing heterozygotes only with clear homozygotes avoids litters with lethal affected kittens.\n- Document the genetic status of the breeding animals.

The variant is co-dominant and lethal in homozygosity; affected kittens are born alive with a severe facial defect and meningoencephalocele, and euthanasia is indicated. Prevention is based on genotyping breeding animals. Do not confuse the normal brachycephaly of the breed with homozygous frontonasal dysplasia.

1. Lyons LA et al. 2016. Aristaless-Like Homeobox protein 1 (ALX1) variant associated with craniofacial structure and frontonasal dysplasia in Burmese cats. Developmental Biology. PMID: 26610632
2. OMIA:002717-9685. Frontonasal dysplasia, ALX1-related in Felis catus. Online Mendelian Inheritance in Animals.