Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory bone disease of unknown etiology. Clinically, the affected children present with recurrent fever and inflammatory bone lesions. Interestingly, CRMO patients frequently develop other chronic inflammatory disorders including psoriasis and inflammatory bowel disease. Several observations support that CRMO has a genetic basis: 1) There are reports of familial occurrence of the disease including affected siblings, concordance in monozygotic twins and a report of an affected father and child. 2) There is a monogenic syndrome that includes CRMO as a major clinical component. 3) There is a report of a susceptibility locus for isolated CRMO on chromosome 18q and 4) There is a spontaneously occurring mouse model with clear autosomal recessive inheritance. This gene has been mapped to murine chromosome 18, in a region that shares homology to human chromosome 18q. This proposal aims at refining the location of CRMO gene by analyzing clinical and genotypic data on nuclear families with an affected individual, in search of an association. Our ultimate goal is gene identification. Additionally, due to the frequent presence of co-morbid conditions such as psoriasis, identification of the CRMO gene may pinpoint an inflammatory pathway critical in the development of other chronic inflammatory disorders. Our specific aims are as follows: 1) Collect clinical data and DNA samples from at least 120 CRMO patients and their parents. 2) Perform association studies by genotyping all families for markers in region with homology to the mouse chromosomal locus. The data will then be analyzed using a transmission disequilibrium model to test for an association between the specific marker and the CRMO phenotype. If an association is found, future studies will be conducted aimed at determining the gene defect that is responsible for susceptibility to CRMO and dissecting the inflammatory pathway(s) that is affected. In doing so, we will shed light not only on the etiology of this rare disease, but also on an inflammatory pathway, that when altered, can lead to the development of more common inflammatory disorders such as psoriasis and inflammatory bowel disease.