OMIA:002717-9685 : Frontonasal dysplasia, ALX1-related in Felis catus (domestic cat)

Categories: Craniofacial phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 601527 (gene) , 613456 (trait)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal co-dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2016

Species-specific description: Information about the ALX1 variant in Burmese cats was previously presented under 'OMIA:001551-9685 : Brachycephaly in Felis catus'. As the variant causes lethal frontonasal dysplasia in animals that are homozygous for the variant, this entry was created [13/6/2023]. As summarised by Lyons et al. (2016), "The Burmese is a cat breed with an extreme brachycephalic phenotype . . .. In the late 1970's, a male Burmese cat in the USA with a more brachycephalic head type became a highly popular sire and his lineage became known as the “Contemporary” Burmese . . . . The head type was found to be heritable, however, offspring from “Contemporary” style mating produced a craniofacial defect in 25% of offspring (Noden and Evans, 1986 and Sponenberg and Graf-Webster, 1986). The abnormality is characterized by agenesis of all derivatives of the medial nasal prominence; lateral duplication of most derivatives of the maxillary process; including the canine teeth and whiskers fields; telencephalic meningoencephalocele; and secondary ocular degeneration . . . . The midline facial defect is autosomal recessive, however, carriers of the mutation are more brachycephalic individuals than wildtype and were positively selected in the breed, thus the trait has also been described as co-dominant. Affected kittens were generally born live and require euthanasia as the condition is incompatible with life. The heterozygous cats became the hallmark phenotype of the “Contemporary” Burmese and the predominant winners at cat shows."

Mapping: Lyons et al. (2016) reported that "Family-based linkage analysis localized the trait to cat chromosome B4".

Molecular basis: Lyons et al (2016): "A long-term project that initiated with targeted linkage analysis, and, as domestic cat genomic resources improved, progressed to identity by descent mapping, homozygosity mapping and a genome-wide case-control association study (GWAS) suggests ALX1 as a major gene controlling craniofacial structure and the variant in ALX1 is associated with the Burmese brachycephaly and the craniofacial abnormality". "Sequence analysis identified a 12 bp in frame deletion in ALX1, c.496delCTCTCAGGACTG, which is 100% concordant with the craniofacial defect and not found in cats not related to the Contemporary Burmese."

Breed: Burmese (Cat) (VBO_0100053).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ALX1 ALX homeobox 1 Felis catus B4 NC_058374.1 (107851193..107872185) ALX1 Homologene, Ensembl , NCBI gene


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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
550 Burmese (Cat) Brachycephaly ALX1 deletion, small (<=20) Naturally occurring variant Felis_catus_9.0 B4 g.110088245_110088256del c.497_508del p.(A166_T169del) XM_003989090.4; XP_003989139.1; published as c.496delCTCTCAGGACTG 2016 26610632 Genomic position in Felis_catus_9.0 provided by Leslie Lyons and Reuben Buckley.

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002717-9685: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2016 Lyons, L.A., Erdman, C.A., Grahn, R.A., Hamilton, M.J., Carter, M.J., Helps, C.R., Alhaddad, H., Gandolfi, B. :
Aristaless-Like Homeobox protein 1 (ALX1) variant associated with craniofacial structure and frontonasal dysplasia in Burmese cats. Dev Biol 409:451-8, 2016. Pubmed reference: 26610632. DOI: 10.1016/j.ydbio.2015.11.015.
1986 Noden, D.M., Evans, H.E. :
Inherited homeotic midfacial malformations in Burmese cats. J Craniofac Genet Dev Biol Suppl 2:249-66, 1986. Pubmed reference: 2878018.
Sponenberg, D.P., Graf-Webster, E. :
Hereditary meningoencephalocele in Burmese cats. J Hered 77:60, 1986. Pubmed reference: 2937834.

Edit History

  • Created by Imke Tammen2 on 13 Jun 2023
  • Changed by Imke Tammen2 on 13 Jun 2023