Evidence Of A New Hereditary Joint Disorder

A 49-year-old male, "MM1" had endured jointpain, invasive treatment, and frustration for most of his life. At age3, he was labeled with "abnormal bone structure" and subjected toimmobilization of both legs. At age 10, he began to complain of kneeand hip pain. By age 13, he had lost significant hip mobility and hisleft leg was shorter than his right. At age 16, he underwent a surgeryto separate the hip and insert a plate. Eventually, in his 40s, he hadhis hip replaced completely. Over the years, MM1 was misdiagnosed withvarious disorders, including Osgood-Schlatter disease,Legg-Calvé-Perthes disease, and spondylo-epiphyseal dysplasia. But whatmade his case clinically compelling was his children. MM1 is the fatherof 3 – 2 daughters, 1 son – all of whom suffered similar symptoms,beginning in the preteen years and continuing into adulthood. All 3children have had multiple arthroscopic procedures – on the knees,hips, and shoulders – for diagnostic and therapeutic purposes. Bothdaughters have had total hip replacement surgery. To the research team,this suggested a terribly destructive joint disease with a stronghereditary component.

To gain a clearer sense of this syndrome'sdistinctive signs, the researchers examined blood samples of both theaffected family members and unaffected relatives – MM1's parents and 4siblings – for single nucleotide polymorphisms (SNPs) in the chromosome2 region which are known to influence bone and cartilage development.Two SNPs were identified in all 4 affected family members. Yet, becausethe same SNPs were also present in MM1's unaffected mother and 2 of 4of his unaffected siblings, their role in the condition wasinconclusive.

The researchers also analyzed radiographic andarthroscopic findings in all 4 of the affected family members.Radiographs showed degenerative changes in the hips of all affected. Ofparticular interest, however, was the unusual arthroscopic evidence.

Inall 4 of the affected family members, researchers observed excessivetissue fluid and large loose bodies. What's more, they found somethingcommon, and bizarre, about the nature of each subject's cartilage: itsvulnerability to "bubbling" and peeling off in layers to expose bone,at a very early age. In OA, cartilage--the body's natural shockabsorber--gradually erodes from the toll of inflammation. The increasedstress on the bones often leads to joint damage. In this novelsyndrome, cartilage de-bonds and strips away at a radical rate, leavingbones completely unprotected and joints exceptionally susceptible toshattering.

"Further studies elucidating the mechanisms leadingto the delamination of cartilage from bone in this family," notes Dr.Moskowitz, Senior Study Investigator, "may provide insights intocartilage-bone interaction in other forms of joint degeneration."

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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.