A 49-year-old male, "MM1" had endured joint pain, invasive treatment, and frustration for most of his life. At age 3, he was labeled with "abnormal bone structure" and subjected to immobilization of both legs. At age 10, he began to complain of knee and hip pain. By age 13, he had lost significant hip mobility and his left leg was shorter than his right. At age 16, he underwent a surgery to separate the hip and insert a plate. Eventually, in his 40s, he had his hip replaced completely. Over the years, MM1 was misdiagnosed with various disorders, including Osgood-Schlatter disease, Legg-Calvé-Perthes disease, and spondylo-epiphyseal dysplasia. But what made his case clinically compelling was his children. MM1 is the father of 3 – 2 daughters, 1 son – all of whom suffered similar symptoms, beginning in the preteen years and continuing into adulthood. All 3 children have had multiple arthroscopic procedures – on the knees, hips, and shoulders – for diagnostic and therapeutic purposes. Both daughters have had total hip replacement surgery. To the research team, this suggested a terribly destructive joint disease with a strong hereditary component.
To gain a clearer sense of this syndrome's distinctive signs, the researchers examined blood samples of both the affected family members and unaffected relatives – MM1's parents and 4 siblings – for single nucleotide polymorphisms (SNPs) in the chromosome 2 region which are known to influence bone and cartilage development. Two SNPs were identified in all 4 affected family members. Yet, because the same SNPs were also present in MM1's unaffected mother and 2 of 4 of his unaffected siblings, their role in the condition was inconclusive.
The researchers also analyzed radiographic and arthroscopic findings in all 4 of the affected family members. Radiographs showed degenerative changes in the hips of all affected. Of particular interest, however, was the unusual arthroscopic evidence.
In all 4 of the affected family members, researchers observed excessive tissue fluid and large loose bodies. What's more, they found something common, and bizarre, about the nature of each subject's cartilage: its vulnerability to "bubbling" and peeling off in layers to expose bone, at a very early age. In OA, cartilage--the body's natural shock absorber--gradually erodes from the toll of inflammation. The increased stress on the bones often leads to joint damage. In this novel syndrome, cartilage de-bonds and strips away at a radical rate, leaving bones completely unprotected and joints exceptionally susceptible to shattering.
"Further studies elucidating the mechanisms leading to the delamination of cartilage from bone in this family," notes Dr. Moskowitz, Senior Study Investigator, "may provide insights into cartilage-bone interaction in other forms of joint degeneration."
Article: "A Newly Described Hereditary Cartilage Debonding Syndrome," D. Holderbaum, T. Malvitz, C.J. Ciesielski, D. Carson, M.P. Corr, and R.W. Moskowitz, Arthritis & Rheumatism, October 2005; 52:10; pp. 3300-3304.
Journal
Arthritis & Rheumatism