Congenital Myasthenic Syndrome (CMS)

in Sphynx Cats

CMS is one of the inherited diseases in the Sphynx for which we are actually in quite a good position when it comes to prevention. We know the variant responsible for the disease, we know how it is inherited and there is a DNA test available.

That makes it very different from HCM, where genetics are considerably more complicated and a DNA result cannot replace cardiac screening.

Congenital myasthenic syndrome is a neuromuscular disease. In Sphynx and Devon Rex cats it is associated with a variant in the COLQ gene, c.1190G>A (p.Cys397Tyr). The disease has been described under several different names in older literature, including hereditary myopathy and muscular dystrophy, which is worth knowing when looking through older papers.

COLQ is involved in the normal function of the neuromuscular junction, which is basically where the signal from a nerve reaches a muscle. In affected cats that communication does not work properly and the result is muscle weakness and abnormal fatigability.

What does CMS look like?

Signs usually appear in young cats and weakness is the main problem.

Affected kittens may tire very easily and become noticeably weaker after exercise, excitement or stress. Weakness can affect the limbs and the muscles supporting the head and neck, and some cats adopt a fairly characteristic posture where they rest their front legs or chest on a raised object.

More severely affected cats can have difficulty swallowing and megaoesophagus has also been reported. The severity is not identical in every affected cat, so CMS does not necessarily look exactly the same in all of them.

How is CMS diagnosed?

If a cat is already showing weakness, a genetic test should not really be treated as a substitute for a veterinary investigation. There are other reasons a cat can become weak or exercise intolerant and those still need to be considered.

Historically, affected Sphynx and Devon Rex cats were investigated using neurological examinations, electromyography, muscle biopsies and other tests. That work eventually helped establish that this was a disorder of neuromuscular transmission rather than simply a primary muscle disease.

But for the inherited form we are talking about here, there is now a much easier way of identifying the genetic status of a cat.

A DNA test can look directly for the known COLQ variant.

And for breeding purposes, this is really the important part because a perfectly healthy-looking cat can be a carrier. You cannot tell by looking at it.

What does the DNA result mean?

CMS is autosomal recessive, so a cat needs two copies of the disease-associated variant to be genetically affected.

A result can therefore come back as clear, carrier or affected.

N/N — Clear

The cat has two normal copies and does not carry the tested CMS variant. It cannot pass this variant to its kittens.

N/CMS — Carrier

The cat has one normal copy and one copy of the CMS variant.

A carrier is not an affected cat and is not expected to develop this form of CMS. It can, however, pass the variant to its kittens.

This distinction matters because “carrier” is sometimes interpreted as though there is something clinically wrong with the cat. With a recessive condition that is not what the result means.

CMS/CMS — Affected

The cat has inherited the CMS variant from both parents and has the genotype associated with the disease.

The breeding combinations are therefore quite straightforward.

Two clear cats cannot produce an affected kitten. A clear cat and a carrier can produce clear and carrier kittens, but not affected kittens. If two carriers are bred together, affected kittens become possible.

So unlike some of the much more complicated genetic questions in the Sphynx, there is not really much uncertainty here. We know what we are testing for and we know how it is inherited.

CMS and breeding Sphynx cats in the UK

This is also one area where the GCCF has gone further than simply recommending a health test.

CMS status forms part of the GCCF Sphynx Registration Policy for cats going onto the Active Register, which is the register used for breeding cats.

A cat can be shown to be genetically clear through its own DNA test or through documented clear ancestry where the GCCF requirements for inherited status are met. In other words, a cat does not necessarily need to be tested again if its clear status can already be established from its parents or pedigree.

The practical outcome is the important bit: Sphynx cats used for breeding under GCCF need to have a documented CMS-clear status.

And I think this is a good example of where genetic testing actually works very well in a breeding programme. There is a known pathogenic variant, the inheritance is straightforward and affected kittens can be prevented.

Among the major cat associations I have checked, GCCF is the one where I can verify an actual Sphynx-specific CMS requirement in the registration rules, rather than CMS simply appearing on a list of tests that breeders may choose to do.

How common is CMS?

This is where I would be careful with numbers.

In the original molecular study, three carriers were found among 81 European Sphynx cats tested, which worked out at 3.7% in that particular sample.

I would not turn that into “3.7% of Sphynx are CMS carriers”.

It was 81 cats from a particular population at a particular time. It tells us that the variant was present in the breed; it does not give us a current worldwide carrier frequency.

And really, current prevalence is not the most important issue here anyway.

Even if a disease-associated variant becomes uncommon because breeders have been testing for it for years, that is not a reason to stop knowing the status of breeding cats. If anything, it may be evidence that screening has done exactly what it was supposed to do.

CMS is one of the conditions where we do not need to guess. We have a direct DNA test, we understand the inheritance and we can avoid producing affected kittens.

References:

Abitbol M, et al.A COLQ Missense Mutation in Sphynx and Devon Rex Cats with Congenital Myasthenic Syndrome.2015.

Gandolfi B, et al.COLQ variant associated with Devon Rex and Sphynx feline hereditary myopathy. 2015.

UC Davis Veterinary Genetics Laboratory — Sphynx and Devon Rex CMS⁠ https://vgl.ucdavis.edu/test/sphynx-and-devon-rex-cms

GCCF Sphynx Registration Policy⁠: https://www.gccfcats.org/wp-content/uploads/2021/10/Sphynx-Registration-Policy-updated-2017.pdf