Complex Vertebral Malformation (CVM)

Also known as

Scoliosis

Description

CVM is a recessive genetic defect that results in embryonic death, abortion or deformed calves that may be stillborn or alive at birth. CVM is a genetic condition caused by a recessive gene resulting from a mutation. Since it is recessive, this means an animal must receive a copy from each parent to be affected.

Heterozygous individuals that carry one copy of the faulty gene and one copy of the normal gene have no signs of the defect but may pass it to some of their offspring

The CVM syndrome was first found in Danish Holstein cattle in 1999. During the following years it was found in the U.S., United Kingdom, Netherlands, and Japan.
 
At this point, the disease has been reported only in Holstein cattle and no other breeds. Bulls that have been identified as carriers include T Klassy, KOL Nixon, T Burma, Etazon Lord Lily and Carlin-M Ivanhoe Bell.

Carlin-M Ivanhoe Bell was a popular bull in the 1980’s whose semen was used for two decades in international Holstein breeding because of the exceptional milk production he passed on to his daughters. This bull founded an important and worldwide breeding line.

Consequently, carriers of CVM have been identified among sires used for artificial insemination in many countries.

Retrospective studies traced the origin of the defective gene to his sire, the U.S. Holstein sire Penstate Ivanhoe Star (US1441440, born in 1963). His son Carlin-M Ivanhoe Bell (US1667366) received the defective gene for CVM and was also a carrier of Bovine leukocyte adhesion deficiency (BLAD).

The BLAD and CVM genes are located in different chromosomes. When Penstate Ivanhoe Star, was tested, he was also found to be a carrier of both CVM and BLAD.

Carlin-M Ivanhoe Bell’s paternal grandsire Osborndale Ivanhoe, however, carried only BLAD, so scientists think the mutation responsible for CVM occurred somewhere in Carlin-M Ivanhoe Bell’s maternal family.

Because of wide international usage of Carlin-M Ivanhoe Bell and the large number of animals descending from him, the CVM gene is found in Holstein cattle throughout the world. By 1999, more than 30% of the best Holstein sires in both Denmark and Japan were CVM carriers.  A test for CVM was developed in February 2001 and was first used in Denmark.

More than 500 sires used for AI in Denmark have been identified as carriers of CVM, but extensive genotyping of potential breeding sires and culling of carriers have reduced the prevalence to nearly zero. Prior to these measures to limit the prevalence of CVM, this syndrome was probably the most frequent inherited disorder in Holsteins ever recorded.

CVM had a major impact on reproductive performance in Holsteins. One study estimated that 2,200 affected fetuses were produced annually between 1995 and 1999 in Sweden, and the annual loss in Germany was estimated to be more than 8,000 lost fetuses between 1997 and 2000. In Denmark, an estimated 12,000 cases occurred until December 31, 2005. The economic impact of these reproductive problems was considerable.

The main effects of CVM are malformation of the vertebrae—the bones that make up the spine. The neck and sometimes the ribcage are shortened because of badly formed or fused vertebrae. This deformity often leads to a curved spine (scoliosis).

A CVM-affected calf typically has an abnormally short neck and crooked pasterns. Other malformations associated with CVM are abnormal shape of the head, abnormal ribs, contracted carpal joints (knees), and contracted and rotated fetlock joints.

Heart defects, such as major blood vessels in the wrong place, occur in about 50% of cases. Most calves with CVM are either aborted or stillborn. Some do survive birth but die soon afterward.

Signs

• Abortion,
• Stillbirth,
• Low birthweight,
• Twisted spine,
• Short neck,
• Malformation of head and front legs

Cause

CVM is caused by a mutation in the bovine SLC35A3 gene, leading to malformations of the vertebral column. CVM is the first genetic disorder found to be caused by defects in that particular gene. The mutation responsible for CVM is recessively inherited, and carriers of the mutation are normal.

CVM affects fetal development, being a cause of abortions and stillbirths. Affected calves are small (low birth weight) and show a variety of malformations in the vertebrae and heart. Diagnosis based on just visual examination may be difficult due to wide variety in the expression of defects; a definite diagnosis requires DNA testing.

As many as 88% of homozygous (with two copies of the defective gene), CVM-affected fetuses are aborted within 260 days of insemination. A normal bovine pregnancy lasts 280 days. Studies of Danish Holsteins have shown that fetal mortality prior to day 260 is approximately 77%. Only 4 to 5% of CVM affected fetuses are born alive, but they don’t live very long.

A CVM carrier cow may have lower fertility, and abortions lead to lowered milk production. CVM causes abortions through the entire gestation period, leading to repeat breedings. CVM carriers are often culled for these reasons, even if the stockman doesn’t know the actual cause of the problems.

CVM carrier bulls were discovered and eliminated in Europe after a DNA test became available. Some of the best animals were found to be carriers, and their removal led to a period of slowdown in dairy breeding in a number of European countries.

All breeding bulls in Sweden have been tested since the tests became available and carriers are no longer used.

The largest economic impact is from loss of pregnancies due to the large number of aborted fetuses and prolonged calving intervals and early culling of cows.

All Holstein bulls are now tested for the CVM defect and carrier bulls are no longer used in most countries. Thus the number of heterozygotes (carriers) for this defect will rapidly decrease. In the mid-1990’s the Bovine leukocyte adhesion deficiency (BLAD) defect in Holsteins was dealt with and eliminated in the same way.

New defects will turn up in the future (since mutations continually occur in all animals), and will also have to be discovered and dealt with.

Prevention

The best prevention is to not use carrier bulls. All responsible AI studs screened their bulls for CVM and should be able to inform you whether their bulls are carriers or not. If you avoid using carrier bulls you will not have a problem with CVM in your herd. If you need to use carrier bulls, check the pedigree of your cows and avoid using carrier bulls on cows whose pedigrees suggest that they might be carriers.

Treatment

There is no treatment for this genetic disorder.