Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Munchkin

Himalayan

Ehlers-Danlos Syndrome (Cutaneous Asthenia )

Related terms: primary connective tissue disease; cutaneous asthenia; dermatosparaxis, collagen dysplasia; fragile skin syndrome

VeNom term:  Ehlers-danlos syndrome (VeNom code: 683).

Outline: Ehlers-danlos syndrome is a group of connective tissue disorders that are characterised by fragile, stretchy and loose skin, caused by a genetic defect in the production of collagen. In cats affected with Ehlers-danlos syndrome, this defect results in the collagen fibres having an abnormal structure. This weakens the skin and reduces its structural properties, and makes it prone to damage.  

The clinical signs of Ehlers-danlos syndrome are fragile skin and laxity in the joints, due to the alterations to collagen structure and density. Even the slightest scratch can damage and tear the skin of affected animals, leading to scarring. The deficiency in collagen can also affect other tissues of the body, such as the eyes, heart and blood vessels. Ehlers-danlos syndrome can be diagnosed with a skin extensibility test and laboratory examination of skin samples to determine changes to collagen. Severely affected kittens usually will not survive, but cats with a mild or moderate form of the condition generally live a normal lifespan, but they are at risk of frequent skin tears and injury. Skin tears and bruising are common, and the tears can be painful and cause irritation. Owners of affected cats have tried to reduce skin damage by removing sharp or rough objects in the cat’s environment or by declawing the cat but these actions can also affect the cat’s welfare.

It is not clear how many cats suffer from Ehlers-danlos syndrome, but it is a rare condition. We do know that the condition affects Himalayan cats more than other breeds, and is inherited in an autosomal recessive manner. Severely affected cats should not be bred from (ie cats which suffer extremely fragile skin). Mildly affected cats can be bred with non-affected cats but only if there is sufficient family history to determine the non-affected cat does not carry the mutation.


Summary of Information

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1. Brief description

Ehlers-Danlos syndrome is a group of connective tissue disorders characterised by fragile, stretchy and loose skin. The underlying defect is that of an abnormality of collagen structure. Collagen is the main structural protein in various connective tissues of the body, including the skin, where it provides strength, elasticity and durability. Normal collagen allows tissue to be stretched but resists over-stretching and then helps in the tissue returning to its normal shape. In cats affected with Ehlers-danlos syndrome, there is a genetic defect in one of the enzymes that produces collagen, procollagen-peptidase leading to an abnormal structure of collagen fibres. This abnormality weakens the skin and reduces its structural properties, resulting in stretchy, loose skin which is prone to damage.

The clinical signs of Ehlers-danlos syndrome are fragile skin and laxity in the joints, due to the alteration to collagen structure and density. Even the slightest scratch can damage and tear the skin, leading to the formation of scars and subcutaneous haematomatas, which are hard masses of blood under the skin surface. There can be internal problems associated with hollow muscular walled structures, such as herniation (rupturing) of muscular diaphragms and perineum, since collagen is important for their structural integrity. There may be increased susceptibility to infections due to poor wound healing. Administration of intra-venous fluids may also be more difficult in these cats due to weakened blood vessels.

2. Intensity of welfare impact

Affected cats show symptoms from birth, with fragile skin, delayed wound healing and pendulous skin. Skin tears and bruising are common, and such tears can be painful and cause irritation. Affected cats may become lame due to loose joints but they do not appear to suffer pain. The severity of the condition is variable, and some animals may encounter minimal problems with skin looseness or fragility if, for example, they live in carefully controlled environments. 

Female cats affected with Ehlers-danlos syndrome may suffer complications during pregnancy and birth due to the deficiency in collagen, with uterine prolapsed or rupture.

Owners of affected cats can try to reduce skin damage by removing sharp or rough objects in the cat’s environment and avoiding activities which may result in injury. Cats may require declawing to prevent self-injury. This may mean that the cat’s quality of life so far as being able to play, exercise, climb and scratch, as it normally would, are reduced. Declawing may cause short- and long-term pain.

Large or deep tears require stitching by a veterinary surgeon, and cats may need general anaesthesia in order to suture wounds. There may be complications of treatment or surgery due to weakened blood vessels, and secondary effects of infections due to poor wound healing..

3. Duration of welfare impact

There is no treatment for Ehlers-danlos syndrome in animals. Severely affected kittens usually will not survive, but cats with a mild or moderate form generally live a normal lifespan, but are at risk of frequent skin tears and injury.

4. Number of animals affected

It is not clear how many cats suffer from Ehlers-danlos syndrome, but it is a rare condition. We do know that the condition affects Himalayan cats more than other breeds. Ehlers-danlos syndrome affects both males and females.

5. Diagnosis

Skin extensibility can be tested by a veterinarian to diagnose hyper-elasticity of the skin. Ehlers-danlos syndrome can be diagnosed with a laboratory examination of skin samples to determine changes to collagen density and structure

6. Genetics

Ehlers-danlos syndrome is thought to be inherited in an autosomal recessive manner in Himalayan cats. This means that cats which inherit two copies of the genetic mutation, one from each parent, will be affected. If a cat inherits one copy of the gene mutation, i.e. from one parent, and a normal gene from the other parent, then it will not be clinically affected but will carry the genetic mutation and may pass this onto offspring. If a carrier is mated with a healthy (non-carrier), there will be a 25% chance of the offspring being affected

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

A specific genetic test to diagnose Ehlers-danlos syndrome is not available, and so there is so way to tell genetically which animals are affected or likely to become affected. In addition, with affected animals, the severity of the condition is variable, and some animals may not have severe problems with skin fragility.

8. Methods and prospects for elimination of the problem

This condition is rare in cats and severely affected cats should not be bred from (i.e. cats that have extremely fragile skin). In addition to the chance of passing on the condition, female cats affected with Ehlers-danlos syndrome may suffer potential life-threatening complications during pregnancy and birth due to the deficiency in collagen. Mildly affected cats can be bred with non-affected cats but only if there is sufficient family history to determine the non-affected cat does not carry the mutation.


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1. Clinical and pathological effects

Ehlers-danlos syndrome is a group of connective tissue disorders that are characterised by fragile, stretchy and loose skin. The underlying defect is that of an enzyme important in the formation of collagen which results in an abnormality of collagen structure. Collagen is the main structural protein in various connective tissues of the body, including the skin, where it provides strength, elasticity and durability. In animals with normal collagen, collagen allows tissue to be stretched but resists over-stretching and then helps in the tissue returning to its normal shape.

Collagen in the skin is made up of elongated fibrils which lie parallel to the skin’s surface and these are formed through the following process. Initially, the pre-cursor for collagen, procollagen - principally made up of the amino acids glycine and proline, is formed inside cells. When procollagen leaves the cell and enters the extracellular space outside, it is trimmed by the enzyme collagenase, and a single collagen fibre is formed (tropocollagen). Multiple tropocollagen molecules then come together to form collagen fibrils via cross linking and these may be attached to cell membranes. In cats affected with Ehlers-danlos syndrome, there is a genetic defect in procollagen-peptidase, which leads to the accumulation of partially processed type 1 procollagen (Counts et al. 1980), which cannot be converted to normal collagen fibres. The collagen fibres in such animals are smaller, with lower collagen content, large spaces between the fibres, abnormal, fragmented shape and size of the collagen bundles, and altered orientation of the collagen (Holbrook et al 1980).

The clinical signs of Ehlers-danlos syndrome include skin fragility and joint laxity. A skin extensibility test can be used to test the percentage of stretch in the skin, with values greater than 19% being indicative of Ehlers-danlos syndrome (see Figure 1; Matousek 2004). Even the slightest scratch can damage and tear the skin, leading to the formation of scars with a sunken appearance, due to the diminished deposition of collagen (atrophic scars). At the site of trauma, there may be a localised collection of blood that forms a hard mass under the surface of the skin (subcutaneous haematomatas, or ‘pseudotumours’).  

There can be internal problems, associated with hollow muscular walled structures, such as herniation (rupturing) of muscular diaphragm and perinea (Benitah et al 2004), since collagen is important for their structural integrity, although these have been rarely reported in cats. 

Figure 1. Skin hyperextensibility in an 11-year old cat with Ehlers-danlos syndrome. Reproduced with thanks from Matousek (2004) via Elsevier Copyright Clearance Centre (license number: 3842951357441).

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2. Intensity of welfare impact

Affected cats will show symptoms from birth, with fragile skin, delayed wound healing and pendulous skin. Skin tears and bruising are common, especially in areas that are readily subjected to trauma such as the back, ears, head and legs (Sequeira 1999). The tears can be painful and cause irritation, and cats may scratch or rub these areas, causing further irritation and damage. The skin may be hypersensitive, and affected cats may experience discomfort when sensitive or fragile areas of the skin are touched. Affected cats may become lame due to loose joints but they do not appear to suffer pain. There is variation between individuals in the severity of the condition; some animals may not encounter significant problems with skin fragility if, for example, they live in carefully controlled environments. 

Female cats affected with Ehlers-danlos syndrome may suffer complications during pregnancy and birth due to the deficiency in collagen, with uterine prolapsed or rupture.

Owners of affected cats can try to reduce skin damage by removing sharp or rough objects in the cat’s environment and avoiding activities including vigorous grooming or rough and tumble play. Cats may require declawing to prevent self-injury (Benitah et al 2004). This may mean that the cat’s quality of life so far as being able to play, exercise, climb and scratch, as it normally would, are reduced.

Large or deep tears require stitching by a veterinary surgeon or nurse, and cats may need general anaesthesia in order to suture wounds, especially since lidocaine – a local anaesthetic treatment used to numb the skin area – appears to be less effective in cats with Ehlers-danlos syndrome. There may be increased susceptibility to infections due to poor wound healing. Administration of intra-venous fluids may also be more difficult in these cats due to weakened blood vessels.

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3. Duration of welfare impact

There is no treatment for Ehlers-danlos syndrome in animals. Severely affected kittens usually do not survive, but cats with mild or moderate forms generally live a normal lifespan, but are at risk of frequent skin tears and injury due to skin fragility and joint laxity.

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4. Number of animals affected

It is not clear how many cats suffer from Ehlers-danlos syndrome, and the range of severities means that many may not be diagnosed. It is sporadically reported (Scott 1974, Counts et al 1980, Holbrook et al 1980), which suggests it remains a rare condition. We do know that the condition is inherited in Himalayan cats, and so they are more likely than other breeds to be affected. Ehlers-danlos syndrome affects both males and females.

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5. Diagnosis

Skin extensibility can be tested by a veterinarian to diagnose hyper-elasticity of the skin. The index follows a formula - vertical height of the skin fold ÷ body length × 100. For normal cats the index value is less than 19% and a value above this threshold can indicate the cat has Ehlers-danlos syndrome (Matousek 2004).

Ehlers-danlos syndrome can be diagnosed with a laboratory examination of skin samples to determine changes to collagen density and structure. Histopathologic abnormalities include low collagen content, large spaces between the fibres, abnormal, fragmented shape and size of the collagen bundles, and altered orientation of the collagen (Holbrook et al 1980).

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6. Genetics

Ehlers-danlos syndrome is suggested to be inherited in an autosomal recessive manner in Himalayan cats (Counts et al 1980, Holbrook et al 1980). This means that cats which inherit two copies of the genetic mutation, one from each parent, will be affected. If a cat inherits one copy of the gene mutation, ie from one parent, and a normal gene from the other parent (homozygous), then it will not be clinically affected but will carry the genetic mutation and may pass this onto offspring. If a carrier is mated with a healthy (non-carrier), there will be a 25% chance of the offspring being affected.

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

A specific genetic test to diagnose Ehlers-danlos syndrome is not available, and so there is so way to tell specifically which animals are affected or likely to become affected. The gene mutation is recessive, and animals can be affected (two copies of the gene mutation, from each parent), carriers (one copy of the gene mutation, from one parent) or healthy (non-carriers). However, even with affected animals, the severity of the condition is variable, and some animals may not encounter problems with skin fragility.

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8. Methods and prospects for elimination of the problem

This condition is rare in cats and severely affected cats should not be bred from (i.e. cats that have extremely fragile skin). In addition to the chance of passing on the condition, female cats affected with Ehlers-danlos syndrome may suffer potential life-threatening complications during pregnancy and birth due to the deficiency in collagen. Mildly affected cats can be bred with non-affected cats but only if there is sufficient family history to determine they do not carry the mutation (Farrell et al 2015).

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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

 Benitah N, Matousek JL, Barnes RF, Lichtensteiger CA and Campbell KL (2004) Diaphragmatic and perineal hernias associated with cutaneous asthenia in a cat. Journal of the American Veterinary Medical Association 224: 706–709

Counts DF, Byers PH, Holbrook KA and Hegreberg GA (1980) Dermatosparaxis in a Himalayan Cat: I. Biochemical Studies of Dermal Collagen. Journal of Investigative Dermatology 74: 96–99

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

Holbrook KA, Byers PH, Counts DF and Hegreberg GA (1980) Dermatosparaxis in a Himalayan Cat: II. Ultrastructural Studies of Dermal Collagen. Journal of Investigative Dermatology 74: 100–104

Matousek JL (2004) 13 - Disorders of collagen and elastin. Small Animal Dermatology Secrets pp. 105–112. Elsevier

Scott D V (1974) Cutaneous asthenia in a cat, resembling Ehlers-danlos syndrome in man. Veterinary Medicine, Small Animal Clinician 69: 1256–8

Sequeira JL (1999) Collagen dysplasia (cutaneous asthenia) in a cat. Veterinary Pathology 36: 603–606

© UFAW 2016


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