This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.
Specific Aims /ObjectivesDevelopmental dysplasia of the hip (DDH) is a common disease of early childhood in which the normal seating of the femoral head in the acetabulum is disrupted. DDH is manifested in several ways in the pediatric patient, ranging from mild instability of the femoral head with slight capsular laxity, to moderate lateral displacement of the femoral head without loss of contact of the head with the acetabulum, to complete dislocation of the femoral head from the acetabulum. Although the incidence is felt to vary from one to four per 1,000 births, an incidence of up to 13 per 1,000 has been reported. There is a strong genetic component to DDH, with a polygenic component felt to be responsible for the acetabular dysplasia, and a monogenic component felt to be responsible for the lax joint capsule. There is also evidence suggesting a relatively high rate of generalized joint laxity (GJL) in patients with DDH, and defects in collagen have been found in patients with GJL. Moreover, a recent genetic association study has shown evidence for an association between DDH and a collagen gene. We hypothesize that the association between DDH and collagen genes is strongest in children with GJL, and if we subgroup patients with DDH based on the presence or absence of GJL we will be able to identify genes associated with DDH in the subgroup with GJL. We also hypothesize that the subgroup of patients with GJL will demonstrate a pattern of inheritance that is close to Mendelian, whereas those without GJl will show a multifactorial inheritance pattern. The findings from this study will improve our understanding of the pathogenesis of DDH, allow us to provide more accurate genetic counseling, and may allow the targeting of therapies based on the uderlying etiology.
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