Frontonasal Dysplasia

Frontonasal dysplasia comprises a series of disorders that affect facial development, resulting in severe craniofacial malformations. In cases where the variant in the ALX1 gene is present in a homozygous state, this condition becomes incompatible with life.

Symptoms

Frontonasal dysplasia is characterized by the absence of certain parts of the nose and duplication of other facial areas, such as canine teeth and whiskers. This results in a midline facial malformation and sometimes a bulge in the front of the skull (telencephalic meningoencephalocele). In addition, it can cause secondary eye problems. Affected cats are usually born alive but require euthanasia because the condition is incompatible with life. Heterozygous cats have become the characteristic phenotype of the "Contemporary Burmese" breed because of their rounded head.

Disease Management

There is no specific treatment to correct this malformation. Most affected cats are born with this condition and usually require euthanasia.

Genetic basis

This disease follows an autosomal dominant mode of inheritance. Autosomal dominant inheritance means that cats only have to inherit one copy of the mutation or pathogenic variant to be at risk of developing the disease. Each kitten born to a parent carrying one copy of the mutation has a 50% chance of inheriting one copy of the mutation and being at risk for the disease. Breeding between cats carrying genetic variants that can cause disease is not recommended, even if they do not show symptoms.

Technical report

Frontonasal dysplasia is a heterogeneous group of disorders affecting facial development. This condition can be sporadic or inherited, and has been associated with specific genetic abnormalities. Frontonasal dysplasia in Burmese cats shows similarities to the human form of the disease and serves as a biological model. In the Burmese breed, the genetic variant responsible for this dysplasia was identified in the ALX1 gene, which plays a critical role in the development of facial tissues. The variant consists of a c.497_508del deletion in the ALX1 gene that affects the normal function of the gene. The genetic alteration leads to severe craniofacial malformations in its homozygous form and to the development of a characteristic brachycephalic phenotype in its heterozygous state, known as "Contemporary Burmese".

Most affected breeds

Burmese

Bibliography

Lyons LA, Erdman CA, Grahn RA, et al. Aristaless-Like Homeobox protein 1 (ALX1) variant associated with craniofacial structure and frontonasal dysplasia in Burmese cats. Dev Biol. 2016 Jan 15