title: Familial Hydroxyapatite Chondrocalcinosis with Spondyloepiphyseal Dysplasia: Clinical Course and Absence of Genetic Linkage to the Type II Procollagen Gene.
abstract: We describe the course of the articular manifestations in a kindred with familial hydroxyapatite chondrocalcinosis and because of an associated spondyloepiphyseal dysplasia (SED) have investigated the linkage between the disease and markers in the type II procollagen gene (COL2A1). Twenty-seven family members from a large pedigree underwent musculoskeletal and radiographic examinations. In 12 patients, the progression of the disease was evaluated by comparative radiographic surveys obtained 12 years apart. Seven of the 12 family members who were studied in 1978 had severe progression of erosive hand osteoarthritis, whereas there was only minimal progression of the previously observed intervertebral disc or periarticular calcifications. The disease was recognized in seven other siblings from the third generation at a mean age of 24 years. Mild SED was present in several previously and newly diagnosed patients. Nevertheless, no genetic linkage between the disease and COL2A1 polymorphic markers was found. Hydroxyapatite chondrocalcinosis in this kindred displays a variable spectrum of phenotypic manifestations, which include spondyloepiphyseal dysplasia, precocious and progressive erosive hand osteoarthritis, and intervertebral disc and costal cartilage calcification. The gene responsible for the occurrence of hydroxyapatite chondrocalcinosis, osteoarthritis, and mild epiphyseal dysplasia in this family must be one that encodes a protein other than type II procollagen. The mild SED was most easily detected by examining younger affected members. The apatite deposits in this family seem to be secondary to the SED and should be distinguished from those in primary hydroxyapatite disease as in calcific periarthritis.
authors.affiliation: Rheumatology Section, University of La Plata, Buenos Aires, Argentina (J.C.M., A.S.A., C.B., S.J.), Rheumatology Division and Department of Biochemistry and Molecular Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania (R. K.), Division of Rheumatology, Department of Medicine, Cooper Hospital University Medical Center, Robert Wood Johnson Medical School at Camden, University of Medicine and Dentistry of New Jersey, Camden, New Jersey, (A.J.R.).
authors.forename: J C
authors.initials: JC
authors.lastname: Marcos
authors.forename: A S
authors.initials: AS
authors.lastname: Arturi
authors.forename: C
authors.initials: C
authors.lastname: Babini
authors.forename: S
authors.initials: S
authors.lastname: Jimenez
authors.forename: R
authors.initials: R
authors.lastname: Knowlton
authors.forename: A J
authors.initials: AJ
authors.lastname: Reginato