Researchers discover new clinical syndrome leading to severe osteoarthritis

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Researchers discover new clinical syndrome leading to severe osteoarthritis

04 May 2004

Findings may shed light on cartilage breakdown and forms of osteoarthritis.

Researchers from Case Western Reserve University School of Medicine and

University Hospitals of Cleveland, and the University of California, San

Diego have discovered a new clinical syndrome which they have named

hereditary chondrolysis, a rare disabling disease in which the cartilage

debonds from bone, leading to severe generalized osteoarthritis.

The findings, presented at the 50th Annual Meeting of the Orthopedic

Research Society in San Francisco in March, may shed light on cartilage

breakdown and forms of osteoarthritis.

The researchers uncovered two mutations involving the FRZB ( " frisbee " ) gene

located on chromosome 2, which has been implicated in familial

osteoarthritis. In previous laboratory studies done elsewhere, FRZB appears

to be important in the development of human limbs at a young age.

Although the finding of the mutation in both affected and unaffected family

members makes the mutation in and of itself insufficient to cause the

clinical syndrome, it may play a role in what could be a polygenic trait.

" Further studies defining the genetic mutation related to chondrolysis seen

in the family we reported have the potential not only for providing targets

for approaches to treatment in the family, but may provide important

information as to mechanisms of cartilage degeneration seen in the millions

of individuals who suffer from primary osteoarthritis, " said Roland

Moskowitz, M.D., one of the investigators and a professor of medicine at

Case and UHC.

" The known relationship of the FRZB gene to embryonic skeletal development,

and the observation by others that women with hip osteoarthritis have an

increased frequency of this gene add to the significance of our

observations, " said Moskowitz, a leading expert on osteoarthritis.

The researchers made the findings after screening seven families with

familial osteoarthritis looking for specific gene mutations. They discovered

a family referred from elsewhere wherein the father, two daughters and a son

have hereditary chondrolysis. In the family, this disease was so pronounced

that the cartilage peeled off the bone, affecting mostly the shoulders, hips

and knees.

Several affected members of the family developed osteoarthritis in their

first decade of life, and needed joint replacement by the time they reached

their 20s. The youngest child underwent several arthroscopic procedures

beginning at 16. The middle sibling needed a complete hip arthroplasty by

age 26, and a second hip replacement less than two years later.

The lead author of the report is Holderbaum, Ph.D., senior research

associate in Moskowitz's laboratory.

Contact: Stamatis

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216-368-3635

Case Western Reserve University