Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Newfoundland 

Newfoundland

Cranial Cruciate Ligament Rupture

Related terms: cranial cruciate rupture; cranial cruciate disease; cruciate disease

Outline: Newfoundlands are genetically predisposed to degeneration and rupture of the cranial cruciate ligament – one of the ligaments of the knee. It causes pain and lameness, which may be mild or severe depending on the stage of the disease and other factors, and which tends to progress as chronic arthritis develops. The disease is thought to affect more than 20% of individuals of this breed.


Summary of Information

(for more information click on the links below)

1. Brief description

Rupture of the cranial cruciate ligament (CCL) is one of the commonest orthopaedic conditions, most often affecting the stifle joint (the knee) in large breeds of dog (Corr 2009). It is a leading cause of their lameness (Wilkie et al 2006a).

The cranial cruciate ligament helps to stabilise the knee joint. Some sudden, complete ruptures of the CCL occur due to trauma (injury), particularly in active young dogs; however, recently it has been recognised that probably over 75% of cases of rupture are due to a degenerative condition developing in the stifle joint. This leads to inflammation, with partial or full rupture of the CCL occurring as the disease progresses (Harasen 2007). This degenerative condition has been found to have a major inherited component in Newfoundland dogs (and probably in other dog breeds) (Wilkie et al 2006a).

The acute form of the disease causes sudden non weight-bearing lameness in affected animals whilst the degenerative disease tends to cause more chronic (long term) intermittent lameness which rapidly worsens if the ligament completely ruptures. If left untreated (and also often with treatment) joint inflammation and instability lead to arthritic changes and permanent pain, lameness and disability. In many cases both knees become affected – occasionally at the same time and often within a year of each other.

Surgical treatment is thought to be necessary for large breeds of dogs, such as Newfoundlands, in order to restore acceptable function in the joint. There are various surgical options depending on the circumstances. Recovery takes time and arthritic changes may develop after surgery.

2. Intensity of welfare impact

CCL disease and rupture causes varying levels of pain and disability. If left untreated, osteoarthritis develops causing permanent pain and disability affecting quality of life. Even with surgery full joint function may not return.

Veterinary diagnosis, surgery and physiotherapy can all cause significant stress and discomfort for the dogs, and pain-relieving medication can have significant side effects.

3. Duration of welfare impact

The disease can occur at any age but is commonly first seen in Newfoundlands at around four years of age. Affected dogs may suffer weeks to months of pain and lameness prior to diagnosis of the disease and if osteoarthritic changes occur these can cause life-long pain and disability. Full recovery from surgical treatment may take months.

4. Number of animals affected

Several studies have shown that Newfoundlands are predisposed to CCL rupture from an early age (Whitehair et al 1993, Duval et al 1999, Wilkie et al 2006a). It has been suggested that the prevalence is over 20% in this breed (Wilkie et al 2006a).

5. Diagnosis

Rupture of the cranial cruciate ligament (CCL) may be suspected in any Newfoundland with hind limb lameness because of the prevalence of the disease in this breed (Harasen 2007). Diagnosis is often confirmed through orthopaedic examination and manipulation of the joint, and, in some cases, by radiography, examination of joint fluid, arthroscopy and CT or MRI scans.

6. Genetics

In Newfoundlands, predisposition to the chronic form of CCL disease and rupture seems to be inherited as a simple recessive condition that has incomplete penetrance (Wilkie et al 2006a). Thus, only dogs with two mutant genes (one from each parent) may be predisposed to the condition and, of those, only about 51% will exhibit the condition because the extent to which the disease progresses is additionally partly due to environmental factors too (Wilkie et al 2006a).

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

Although carriers (animals which are unaffected themselves but which can pass the disease on to their offspring) may well exist, currently it is not possible to identify carriers or animals that are at risk of developing the condition. Puppies with one or two parents which have had CCL rupture have a high risk of developing the condition, but having healthy parents does not guarantee freedom from the condition.

8. Methods and prospects for elimination of the problem

The genes that cause the disease have yet to be identified. Research into this is underway at Iowa State University, USA, with the aim of developing a genetic test for the condition (Wilkie et al 2006a). Such a test would greatly assist in tackling the problem. It is currently difficult to select against the disease as it often does not show until after breeding age and some unaffected individuals carry and pass on the mutant gene to their offspring.

 

For further details about this condition, please click on the following:
(these link to items down this page)


1. Clinical and pathological effects

Rupture of the cranial cruciate ligament (CCL) is one of the commonest orthopaedic conditions, most often affecting the stifle joint (the knee) in large breeds of dog (Corr 2009). It is a leading cause of their lameness (Wilkie et al 2006a).

The stifle (knee) is a complex joint between the lower end of the femur (thigh bone) and the upper end of the tibia (shin bone). The patella (knee cap bone) is in the tendon of the quadriceps muscle, that passes over the front of the joint. At the rear of the joint, there are several other small bones - the pea-sized fabellae. Located within the joint, and sandwiched between the ends of the femur and tibia, are two discs of cartilage called the menisci. These act as shock-absorbers

The joint is stabilized both by tendons, including the patella tendon, which attaches to the tibial tuberosity (a prominence on the front of the tibia), and by several ligaments. On either side of the stifle, there are collateral ligaments, running from the femur to the tibia (and fibula laterally); inside the joint are the two cruciate ligaments, so called as they cross over each other. The caudal cruciate ligament attaches the cranial (front) surface of the femur to the caudal (back) surface of the tibia, and the cranial cruciate ligament attaches the caudal femur to the cranial tibia. The canine stifle joint is somewhat flexed (bent) when weight bearing and the cranial cruciate ligament is designed to stop the tibia slipping forward relative to the femur, and to prevent excessive internal rotation of the tibia and hyperextension (over straightening) of the joint (Miller 1996). It consists of two main bands of tissue – a craniomedial band, which is taut at all times ie in flexion and extension, and a caudolateral band which is larger and taut only in extension (Miller 1996).

Some sudden (acute), full ruptures of the cranial cruciate ligament (CCL) occur due to trauma (injury), particularly in active young dogs; however, recently it has been recognised that probably over 75% of cases of rupture are due to a degenerative condition in the stifle joint. This leads to inflammation with partial or full rupture of the CCL as the disease progresses (Harasen 2007). This degenerative process is called cruciate disease by some authors eg Harasen (2007).

The underlying disease process is not fully understood. It has been suggested that various factors may play a role in it, including ageing, obesity and genetics (Harasen 2007). There is evidence that the ligaments are weaker in Rottweilers than in other dogs (Wingfield et al 2000) and that there is a genetic component to the risk of CCL rupture in Newfoundlands (Wilkie et al 2006a). This is likely in some other breeds also. Wilkie et al (2006a) suggested that a mutant gene predisposes the ligament to degeneration and rupture. Neutered animals may be more at risk than entire ones (Duval et al 1999). Corr (2009) listed various factors that have been implicated in cruciate disease, but which are unsubstantiated, including rheumatoid arthritis, conformational deformities, narrow intercondylar notch width (the shape of the distal end of the femur – the part furthest from the body), obesity, inactivity in puppyhood, and repetitive chronic trauma.

Cranial cruciate ligament disease can appear in two distinct ways, as outlined below.

  1. The first is acute lameness due to complete sudden rupture of the CCL caused by trauma. In these cases, the dogs are usually completely non weight-bearing on the affected hindlimb. With time, rest and pain-relieving medication they may improve and start to bear weight in 7 to 10 days (Corr 2009). The diagnosis is usually straightforward and may be made after veterinary examination and manipulation of the joint (Corr 2009). Affected dogs will sufferpain due to the damaged ligament, the instability (excessive movement) of the joint, and from resulting inflammation.
  2. The second form is due to chronic, gradual degeneration of the ligament. In these cases, which are harder to diagnose, pain and inflammation may start within the joint, as the ligament degenerates, before it ruptures. This pain and inflammation result in intermittent, chronic lameness in affected animals, which tends to be of a lower grade and in which  the dog still weight-bears to some extent (Corr 2009). This lameness often responds to rest but reoccurs once exercise is reintroduced (Corr 2009). It is thought that the degenerative process in the ligament initiates painful inflammation within the joint before any instability of the joint occurs (Harasen 2007). However, it is not known whether the joint inflammation or the ligament degeneration occurs first.

As the ligament degenerates it may partially or fully rupture, leading to an acute worsening of signs as the joint becomes unstable. Many affected dogs have concurrent damage to the caudal cruciate ligament and severe joint inflammation (synovitis). The apparently greater intensity of inflammation seen in these animals is thought to provide some evidence that this plays a part in subsequent ligament degeneration (Sumner et al 2010).

About 50% of affected dogs also have damage to the meniscal cartilages and this may contribute to the pain and lameness suffered (Harasen 2007). In some cases both legs are affected at the same time. Such dogs are severely disabled.  It has been found that 30-40% of dogs with CCL rupture will, at some time, suffer rupture of the CCL in the other stifle, often within weeks to months (Harasen 2007, Corr 2009).

Because of the inflammation and/or instability, osteoarthritis (degenerative joint disease) develops within the affected joints. In osteoarthritis there are progressive changes to the cartilage of the joint and varying levels of inflammation and ongoing damage to other joint structures - the joint capsule, the synovial fluid of the joint and the surrounding bone – that are irreversible.

Surgical treatment of rupture of the CCL is considered to be necessary in dogs of over 20kg bodyweight, such as Newfoundlands, in order to restore acceptable function in the leg (Harasen 2007). Several  surgical interventions have been used, these include extracapsular (staying outside the joint) stabilization methods, intracapsular stabilization methods, and more invasive methods such as tibial plateau levelling osteotomy and tibial tuberosity advancement, all of which have advantages and disadvantages. Which is the most appropriate depends on individual circumstances. Corr (2009) suggested that tibial plateau levelling osteotomy (TPLO) procedures - in which the bone of the joint is levelled off to stabilize it -may result in the quickest recoveries for dogs of large and giant breeds such as the Newfoundland. Harasen (2007) suggests these procedures, though at risk of more complications, seem to be associated with better results in dogs of large breeds and less post-operative osteoarthritis. In a study of 438 cases treated with TPLO less than 10% of cases had radiographical signs of osteoarthritis in the joints two years after surgery (Jandi et al 2006).

Return to top

2. Intensity of welfare impact

In most dogs, CCL rupture causes chronic, intermittent low-grade pain and disability until diagnosis and treatment. A few suffer more severe, acute pain and disability. If left untreated, permanent disabling osteoarthritis is very likely to develop causing constant pain and affecting quality of life permanently.

Disabling osteoarthritis develops despite surgery in some cases and the treatments can also have a significant welfare impact due to the stress and discomfort of recurrent veterinary visits, interventions, manipulations, physiotherapy and surgery. Commonly used pain-relieving, anti-arthritis medication can have significant side-effects such as kidney damage, and gastrointestinal ulcerations (Ramsey 2011).

Return to top

3. Duration of welfare impact

CCL rupture can occur at any age, but Whitehair et al (1993) studying all breeds of dogs found a peak in incidence at between 7 to 10 years, with this peak tending  to occur earlier in dogs of heavier breeds. Wilkie et al (2006a) in their study of CCL rupture in Newfoundland dogs found the median age at diagnosis was just over 4 years.

In cases where there is sudden and dramatic onset of the disease, it is often diagnosed rapidly but where signs develop more slowly the affected dogs may suffer weeks to months of lameness and pain prior to diagnosis and treatment. For dogs of over 20kg body weight, surgical treatment is considered to be essential for the restoration of an acceptable level of function (Harasen 2007). Even with treatment, the joint may develop some degree of osteoarthritis but, without it, joint instability will result in more severe osteoarthritis leading to life-long disability, pain and the need for pain-relieving medication.

Return to top

4. Number of animals affected

In a study in the USA, it was found that just under 20% of all dogs examined for lameness at University hospitals had CCL rupture (Johnson et al 1994). Newfoundlands are predisposed to CCL rupture from an early age (Whitehair et al 1993, Duval et al 1999) and Wilkie et al (2006a) reported a prevalence of 22% (ie about 1 in 5 animals had the condition). These authors suggested that 60% of Newfoundlands may carry the mutated gene which predisposes individuals to CCL disease (Wilkie et al 2006a).

Return to top

5. Diagnosis

CCL rupture may often be suspected in a Newfoundland with hindlimb lameness because of the known high prevalence in the breed (particularly in young to middle-age dogs) but confirming the diagnosis is sometimes difficult (Harasen 2007, Corr 2009). Definitive diagnosis usually involves thorough orthopaedic examination and palpation of the joint, often performed under sedation or anaesthesia. On palpation, atrophy of the quadriceps muscle (loss of muscle mass at the front of the thigh) may be detected, as may stifle joint effusion (swelling) - evident as a less distinct patella ligament. Thickening of the medial aspect of the joint (called a medial buttress) can often be felt in dogs that have been affected for a few weeks or more (Corr 2009). Two joint manipulation tests may help in diagnosis: the cranial drawer test, and the test for cranial tibial thrust. The cranial drawer test can be difficult to perform and is painful in conscious animals so may be carried out under sedation or anaesthesia. Although many cases are diagnosed by examination and palpation alone (Harasen 2007), additional diagnostics are sometimes necessary. Radiography (x-rays) of the joint may give some indications of joint swelling and inflammation and aspiration and examination of joint fluid may also be useful for detection of inflammation within the joint. Arthroscopy (visual examination of the inside of the joint using a keyhole incision and endoscope to view the joint) can reveal damaged ligaments. Contrast CT (computer tomography) arthrography can be useful and MRI (magnetic resonance imaging) is the best diagnostic test in humans with CCL rupture, but can be prohibitively expensive in dogs (Corr 2009).

Return to top

6. Genetics

It has been shown that there is a genetic component to the risk of CCL rupture in Newfoundland dogs. Wilkie et al (2006a) demonstrated that a single recessive gene with incomplete penetrance was the likely mode of inheritance and their study suggested a heritability of 0.27. That is, genetic variation in the breed accounts for 27% of the occurrence of the disease and environmental factors accounts for 73%.

Dogs with two recessive mutant genes (one from each parent) could develop the condition but, as penetrance of the gene has been found to be 51%, only about half of these will. The other 49%, with the homozygous recessive genotype (2 recessive genes), will not develop CCL disease. Dogs with just one recessive gene are also unlikely to develop CCL disease, but are carrier animals that have the potential to pass on the mutant gene to their offspring.

Work to identify the gene that causes the disease is progressing. Wilkie et al (2006b) found a significant correlation between a mutation on chromosome 3 and CCL rupture.

Return to top

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

At present, as far as we are aware, there is no way to identify carrier animals (animals that have the potential to pass on the disease to their offspring but may themselves otherwise be unaffected) or those that have the potential to develop CCL disease. It is recommended that only puppies with healthy parents (and other relatives) are purchased. Unfortunately this does not guarantee that the puppies will remain free of cruciate disease as it is thought that healthy carrier animals exist (see above). Also, the disease may not become apparent until after breeding age.

Return to top

8. Methods and prospects for elimination of the problem

Selective breeding to tackle this disease is complicated by: the high prevalence of the mutant gene in the breed (thought to be 60%). This is because affected dogs can reach the breeding age years before the disease develops; and because healthy carrier animals exist (Wilkie et al 2006a). Breeding from animals from lines with low prevalence of the disease or out-crossing with unaffected dogs may help reduce the risk of the disease. Identification of the gene and development of a genetic test would greatly aid in tackling the problem.

Until that time Inauen et al (2009) have suggested selective breeding based on the conformation of the tibial tuberosity – a protrusion on the front of the tibia to which tendons attach. They hypothesized that the smaller the width of the tibial tuberosity, the greater the cranial tibial thrust force acting on the joint leading to increased rates of ligament degeneration and rupture. They concluded that only dogs with relative tibial tuberosity widths of greater than 0.9 should be used for breeding. This test is not yet being used as part of a breeding programme as far as we are aware.

Return to top

9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section.

Return to top

10. References

Corr S (2009) Decision making in the management of cruciate disease in dogs. In Practice 31: 164-171

Duval JM, Budsberg SC, Flo GL, and Sammarco JL (1999) Breed, sex, and body weight as risk factors for rupture of the cranial cruciate ligament in young dogs. Journal of American Veterinary Medical Association 215: 811–814

Harasen G (2007) Cruciate Ligament Rupture. On-line VIN associate. http://www.vin.com/Members/Associate/Associate.plx?DiseaseId=453. Accessed 31.5.11

Inauen R, Koch D, Bass M and Haessig M (2009) Tibial tuberosity conformation as a risk factor for cranial cruciate ligament rupture in the dog. Veterinary and Comparative Orthopaedics and Traumatology 22: 16-20

Jandi AS, Kahlon SS and Schulman AJ (2006) Effect of tibial plateau leveling osteotomy on lameness, osteoarthritis, joint motion and post operative meniscal injury in dogs with ruptured cranial cruciate ligament: A 2 year prospective study of 438 cases (abstract). World Veterinary Orthopedic Congress 2006: 15

Johnson JA, Austin C and Breur GJ (1994) Incidence of canine appendicular musculoskeletal disorders in 16 veterinary teaching hospitals from 1980 through 1989. Veterinary and Comparative Orthopaedics and Traumatology 7: 56–69

Miller A (1996) Decision making in the management of cranial cruciate ligament rupture. In Practice: 98-102

Ramsey I (2011) Small Animal Formulary 7th Ed. BSAVA: Gloucester, UK

Sumner JP, Markel MD and Muir P (2010) Caudal Cruciate Ligament Damage in Dogs with Cranial Cruciate Ligament Rupture. Veterinary Surgery 39: 936-41

Whitehair JG, Vasseur PB and Willits NH (1993) Epidemiology of cranial cruciate ligament rupture in dogs. Journal of American Veterinary Medical Association 203: 1016–1019

Wilkie VL, Conzemius MG, Kinghorn BP, Macrossan PE, Weiguo C and Rothschild MF (2006a) Inheritance of rupture of the cranial cruciate ligament in Newfoundlands. Journal of American Veterinary Medical Association 228: 61–64

Wilkie VL, Ruhe A, Conzemius MG and Rothschild MF (2006b) Predisposition to rupture of the cranial cruciate ligament in the dog is genetically associated with chromosome 3 (abstract). World Veterinary Orthopedic Congress 2006: 35

Wingfield C, Amis AA, Stead AC and Law HT (2000) Comparison of the biomechanical properties of rottweiler and racing greyhound cranial cruciate ligaments. Journal of Small Animal Practice 41: 303-307

© UFAW 2011


Credit for main photo above:

By SKern at the German language 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