Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Burmese

Burmese

Burmese Head Defect

Related terms: craniofacial defect; frontonasal dysplasia; telencephalic meningohydroencephalocele

Related conditions: brachycephaly

Outline: A genetic mutation in Burmese cats affects the development of the head and facial areas of the foetus during pregnancy. The craniofacial malformations caused by the condition are immediately apparent from birth and are severe, eg malformation of the lower jaw and nostrils, degeneration of the eyes and ears and protrusion of the brain. Affected kittens can be born alive and require euthanasia as the condition is incompatible with normal or prolonged life.

Burmese head defect is inherited as an autosomal recessive trait, but it is linked with brachycephaly, which causes shortened face and more rounded skull. Cats that inherit only one copy of the genetic mutation (ie from only one parent) will have a brachycephalic head shape. Cats that inherit two copies of the genetic mutation (ie one from each parent) will have the severe and fatal craniofacial defect.  Since brachycephaly is considered by some to be a desirable trait in the breed and the fatal form of the mutation is recessive, there may be many carriers of the condition, and two carriers mated together can produce affected offspring. The genetic mutation is particularly prevalent in the ‘Contemporary’ lines of the Burmese breed, and especially in the USA. A genetic test to identify carriers is available and screening and careful breeding practices should reduce the frequency of the mutation in this breed.


Summary of Information

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1. Brief description

In cats with the genetic mutation that causes ‘Burmese head defect’, there is a disruption of the normal developmental processes that form the skull and facial features in the foetus. There is duplication of the tissue of the upper jaw; affected cats develop two hard palates (the bony roof of the mouth) and two sets of whisker pads. In addition, the region of the skull above the upper jaw does not form properly. Eyes and ears are absent, or malformed, and there is incomplete closure of the fontanelles of the skull. The brain appears to protrude from the skull, although it is generally covered by skin. These craniofacial malformations are severe and immediately apparent at birth. Affected kittens can be born alive but require immediate euthanasia as the condition is incompatible with life.

2. Intensity of welfare impact

Kittens affected with this condition may be stillborn but some can be alive at birth. Such individuals require immediate humane euthanasia delivered by a veterinarian. Kittens with this condition would not be able to eat, drink or breathe normally and would therefore not survive.

3. Duration of welfare impact

Kittens with ‘Burmese head defect’ will not survive and should be humanely euthanized by a veterinarian.

4. Number of animals affected

The genetic mutation is present in both the ‘Traditional’ and ‘Contemporary’ Burmese breed lines worldwide but it is particularly prevalent in the ‘Contemporary’ lines and especially in the USA. A recent study suggested the frequency of carriers of the condition (ie heterozygous cats that are able to pass the defective gene mutation on to their offspring) was 5.7% of the Burmese population (Lyons et al 2016).

5. Diagnosis

The craniofacial malformations are present from birth and are very distinctive and therefore can be diagnosed phenotypically without confusion with other birth defects.

6. Genetics

‘Burmese head defect’ is caused by a mutation in the gene responsible for the development and growth of facial structures in the foetus. It is an autosomal recessive genetic mutation, meaning that cats must inherit two copies of the mutated gene, one from each parent, to be affected. Cats that inherit only one copy, ie from only one parent (heterozygous), do not have the head defect but have the shortened facial structure and rounded skull characteristic of brachycephaly. Heterozygous cats (carrying one copy of the mutation) may pass the mutation on to their offspring.

7. How do you know if an animal is a carrier or likely to become affected?

A DNA test, using blood or saliva, can be used to identify cats that are carriers (heterozygous) of the gene that causes Burmese head defect and those that do not have the defective gene.

8. Methods and prospects for elimination of the problem

DNA tests should be used to identify carriers of the mutated gene in cats used for breeding. Mating two carriers will produce some offspring that are affected by the condition and it is recommended that this is avoided. A cat that carries one copy of the defective gene mated with a cat that does not have the mutation will produce unaffected offspring, although 50% will be carriers of the condition.


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1. Clinical and pathological effects

In cats with the genetic mutation that causes ‘Burmese head defect’, there is a disruption of the normal developmental processes that form the skull and facial features in the foetus. The neural crest is a transient embryonic structure that produces mesenchymal cells, which are a group of unspecialised cells that develop into a whole range of tissues in the embryoincluding the peripheral nervous system, the smooth muscle of the cardiovascular system and the cartilage and connective tissues of the cranium and face (craniofacial). In cats with the genetic mutation causing ‘Burmese head defect’, there is a disruption of the processes in the second trimester of pregnancy whereby the cranium changes shape (cranial morphogenesis) and abnormal craniofacial structural features develop (Uz et al 2010). In affected cats, several structures fail to develop as they normally would (agenesis; Noden & Evans 1986). The medial nasal prominence, that forms the upper lip and nose, does not form properly, and there is duplication of the maxillary process, a triangular bony plate which forms the upper jaw and lower boundaries of the nostrils. The neural tube is the embryo’s precursor to the central nervous system, comprising the brain and the spinal cord. In cats with Burmese head defect, the neural tube fails to close completely during foetal development, leading to a sac-like protrusion of the brain through openings of the skull (meningoencephalocele; Sponenberg & Graf-Webster 1986). Although the eyes and ears may form as normal, affected cats show secondary degeneration due to abnormal foetal growth and development.

The craniofacial malformations associated with this condition are severe and immediately apparent at birth (Figure 1). There is duplication of the tissue of the upper jaw; affected cats develop two hard palates (the bony roof of the mouth) and two sets of whisker pads. In addition, the region of the skull above the upper jaw does not form properly. Eyes and ears are absent or malformed and there is incomplete closure of the fontanelles of the skull. The brain appears to protrude from the skull, although it is generally covered by skin - that may or may not be covered with fur. Affected kittens can be born alive and require immediate euthanasia as the condition is incompatible with life.

Figure 1. a. Head conformation of a traditional Burmese cat. b. the contemporary style with extreme brachycephalic conformation. c. and d. frontal and lateral view, respectively of kitten with Burmese head defect, showing abnormal development of the maxillary processes and ocular and nasal degeneration. Photographs are courtesy of Nancy Reeves, Isabelle Marchand and Richard Katris – Chanan Photography and are reproduced from Lyons et al (2016) under the Creative Commons licence (CC BY-NC-ND).

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2. Intensity of welfare impact

Kittens affected with this condition may be stillborn but some can be alive at birth. Such individuals require immediate humane euthanasia delivered by a veterinarian. Kittens with this condition would not be able to eat, drink or breathe normally and would therefore not survive.

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3. Duration of welfare impact

Kittens with Burmese head defect will not survive and should be humanely euthanized by a veterinarian.

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4. Number of animals affected

The genetic mutation is present in both the ‘Traditional’ and ‘Contemporary’ Burmese breed lines worldwide but it is particularly prevalent in the ‘Contemporary’ lines in the USA - which have a rounded brachycephalic head shape. 

In a study of 488 Burmese stillbirth kittens, 83 were stillborn kittens with the craniofacial defect (17.0%; Lyons et al 2016). Genotyping of 3250 Burmese type cats over 20 years (1992-2012), suggests the frequency of cats carrying one copy of the mutation (ie heterozygous cats that are able to pass the defective gene mutation on to their offspring of the gene) was 4.7% (151 cats) in the USA and European Burmese population (Lyons et al 2016).

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5. Diagnosis

The craniofacial malformations are present from birth and are very distinctive and can be diagnosed phenotypically without confusion with other birth defects.

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6. Genetics

In the late 1970s, a male Burmese cat with a more rounded brachycephalic head type became a very popular sire in the USA and his lineage became known as the Contemporary Burmese. Offspring from matings of these ‘Contemporary’ style cats produce a craniofacial defect in 25% of individuals (Noden & Evans 1986, Sponenberg & Graf-Webster 1986).

The craniofacial malformation is caused by the deletion of 4 amino acids of the homeobox transcription factor ALX1 gene (Lyons et al 2016). In vertebrates, ALX1 regulates the development and survival of structural elements of the face and neck derived from mesenchymal cells from the neural crest (Uz et al 2010). The mutation of the ALX1 gene in Burmese cats disrupts the morphogenesis of the cranium and causes brachycephaly in the heterozygous state – where the cat only has one copy of the defective gene - and the severely dysmorphic congenital abnormality seen in ‘Burmese head defect’ when homozygous – where the cat has inherited two copies of the defective gene.

Burmese head defect is an autosomal recessive genetic mutation (Lyons et al 2016), meaning that cats require two copies of the mutated gene (homozygous), one from each parent, to be affected with the severe craniofacial malformations. However, the trait is described as co-dominant, since cats with only one copy of the mutation (heterozygous), i.e. inherited from only one parent, do not develop the severe malformation of the head but instead are born with a brachycephalic (shortened) facial structure. Heterozygous cats (carrying only one copy of the mutation) will pass a copy of the defective gene onto 50% of their offspring. If a heterozygous cat is mated with another heterozygous, there is a 25% chance of producing offspring that are homozygous (ie affected with the severe craniofacial malformations), and a further 50% of offspring will be heterozygous carriers of the gene.

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7. How do you know if an animal is a carrier or likely to become affected?

Knowledge of the condition in the cat’s family history may highlight whether an individual cat is a possible carrier of the defective gene. Simple DNA tests, available in North America and Europe, can be used to identify the presence of the gene responsible for ‘Burmese head defect’, with good reliability. DNA can be analysed from either blood samples or mouth swabs. The test can identify cats that are carriers (heterozygous).

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8. Methods and prospects for elimination of the problem

Genetic screening and careful breeding practices are valuable tools to reduce and ultimately eliminate the disease (Farrell et al 2015), and these are ongoing for the Burmese breed. The genetic mutation is present in both ‘Traditional’ and ‘Contemporary’ lines worldwide but it is particularly prevalent in the ‘Contemporary’ lines and especially in the USA.   

DNA tests should be used to identify carriers of the mutated gene in cats used for breeding. Ideally, cats that are clear of the condition (not carriers) should be used for breeding, although this may not be possible where pedigree populations are small or isolated. Mating two carriers will produce some offspring that are affected by the condition and so this should be avoided. A cat that carries one copy of the defective gene mated with a cat that does not have the mutation, will produce unaffected offspring, but 50% will be carriers of the condition, so this also should be avoided.

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9. Acknowledgements

UFAW thanks Dr Emma Buckland (BSc PhD), Dr David Brodbelt (MA VetMB PhD DVA DipECVAA MRCVS) and Dr Dan O’Neill (MVB BSc MSc PhD MRCVS) for their work in compiling this section.

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10. References

Farrell LL, Schoenebeck JJ, Wiener P, Clements DN and Summers KM (2015) The challenges of pedigree dog health: approaches to combating inherited disease. Canine Genetics and Epidemiology 2: 3

Lyons LA, Erdman CA, Grahn RA, Hamilton MJ, Carter MJ, Helps CR, Alhaddad H and Gandolfi B (2016) Aristaless-Like Homeobox protein 1 (ALX1) variant associated with craniofacial structure and frontonasal dysplasia in Burmese cats. Developmental Biology 409: 451–8

Noden DM and Evans HE (1986) Inherited homeotic midfacial malformations in Burmese cats. Journal Of Craniofacial Genetics And Developmental Biology. Supplement 2: 249–66

Sponenberg DP and Graf-Webster E (1986) Hereditary meningoencephalocele in Burmese cats. The Journal Of Heredity 77: 60

Uz E, Alanay Y, Aktas D, Vargel I, Gucer S, Tuncbilek G, von Eggeling F, Yilmaz E, Deren O, Posorski N, Ozdag H, Liehr T, Balci S, Alikasifoglu M, Wollnik B and Akarsu NA (2010) Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia. A

© UFAW 2016


Credit for main photo above:

By VikOlliver (en wikipedia) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons