DNA panel specific to the Burmese that combines genetic blood group determination with screening for three hereditary conditions of the breed: GM2 gangliosidosis, congenital craniofacial defect and familial hypokalaemic polymyopathy. GM2 is a lethal lysosomal neurodegenerative disease; the craniofacial defect is a severe congenital malformation; and hypokalaemia is a treatable neuromuscular disorder. It is performed from a buccal swab or blood and identifies carrier and affected animals to plan safe matings.

GM2 is now very rare thanks to the control of carrier lines. Hypokalaemia has been reported in Burmese lines from Europe and Australia at a low frequency. The craniofacial defect appears sporadically and concentrated in specific families; the ALX1 deletion is very common in the modern brachycephalic Burmese (homozygotes are not viable), so the risk lies in matings between two heterozygotes.

- GM2: head tremor, ataxia and progressive paresis from the first months of life, with death or euthanasia before one year
- Craniofacial defect (ALX1 homozygotes): severe congenital craniofacial malformations, generally incompatible with life (stillbirth or early euthanasia)
- ALX1 heterozygotes: brachycephalic phenotype of the modern Burmese, without lethal malformation
- Hypokalaemia: episodes of skeletal muscle weakness with cervical ventroflexion, exercise intolerance and abnormal gait
- Neonatal isoerythrolysis due to blood group incompatibility

GM2 gangliosidosis (hexosaminidase deficiency) was described in Burmese cats in the last decades of the 20th century as a model of the homologous human diseases, and the subsequent identification of the HEXB gene variant made a carrier test available. The congenital craniofacial defect has been recognised in Burmese lines for decades; Lyons and colleagues (2016) demonstrated its association with a deletion in the ALX1 gene and codominant inheritance: heterozygotes present the brachycephalic phenotype typical of the modern standard, while homozygotes for the deletion present severe craniofacial malformations incompatible with life. Burmese hypokalaemic polymyopathy was clinically characterised in Europe and Australia and was associated with a variant in the WNK4 gene, which enabled a DNA test. The AB blood group system was deciphered molecularly in 2007 with the identification of the CMAH gene.

- Never mate two GM2 or hypokalaemia carriers: 25% of the litter would be expected to be affected
- GM2 or hypokalaemia carriers may be mated with clear animals and gradually withdrawn rather than excluded from the programme
- For the ALX1 craniofacial defect, since inheritance is dominant, all modern brachycephalics are heterozygotes for the deletion; heterozygote × heterozygote mating produces 25% lethal malformed homozygotes, 50% brachycephalic heterozygotes and 25% wild-type homozygotes (non-brachycephalic). Know the genotype before mating and avoid heterozygote × heterozygote matings if litters with malformed kittens are to be prevented
- Determine the blood group before mating to prevent neonatal isoerythrolysis
- In kittens with neck ventroflexion, suspect hypokalaemia and consult the veterinarian early: it is treatable

Hypokalaemia is confirmed by serum potassium and creatine kinase (CK) and usually responds well to potassium supplementation; it must be differentiated from other causes of myopathy and weakness. In GM2, measurement of hexosaminidase activity in leukocytes supports the diagnosis, as does the observation of storage vacuoles in tissues. The craniofacial defect requires differential diagnosis with other congenital malformations; diagnostic imaging and post-mortem examination are useful in confirmed cases. Remember that brachycephaly in the modern Burmese and the lethal craniofacial defect share the same ALX1 deletion at different doses: two copies lethal, one copy breed phenotype.

1. Lyons LA et al. 2016, deleción de ALX1 asociada a la estructura craneofacial y displasia frontonasal del burmés. Dev Biol. PMID: 26610632
2. Bighignoli B et al. 2007, mutaciones de CMAH asociadas al grupo AB felino. BMC Genet. PMID: 17553163
3. Gandolfi B et al. 2012, primer modelo animal de hipopotasemia por WNK4 en el burmés. PLoS One. PMID: 23285264
4. Lyons LA 2015, DNA mutations of the cat (revisión). PMID: 25701860