Legg-Calve-Perthes disease, venous and arterial thrombi, and the factor V Leiden mutation in a four-generation kindred.

UNLABELLED: In a 4-generation kindred identified through a 12-year-old female proband with Legg-Calve-Perthes Disease (LCPD) who was found to be heterozygous for the G1691A factor V Leiden mutation (FV), our specific aim was to assess associations of FV with LCPD and with venous and arterial thrombotic events. Despite lethal thromboembolism in 3 family members at ages 21, 35, and 38, retinal artery thrombosis, and deep venous thrombosis, no family members had previously been studied for the FV mutation until kindred screening-genetic counseling was prompted by the discovery of the FV mutation in a child proband with LCPD.

METHODS: In a 4-generation kindred identified through a 12-year-old female proband with LCPD and found to be heterozygous for the FV mutation, we assessed the FV genotype and its association with thromboembolism in 14 of 16 living first- and second-degree relatives.

RESULTS: There was 3-generation vertical and horizontal transmission of heterozygosity for the FV mutation. Of 14 living first- and second-degree relatives, 10 were heterozygous for the FV mutation, including the proband's sister, mother, and maternal grandmother. Of the 14 living relatives, 2 had thrombotic events (retinal artery thrombosis and deep venous thrombosis of the leg). The proband's maternal great-grandfather had a lethal pulmonary embolus at age 35, as did her maternal great aunt at age 38, and a female third cousin at age 21.

CONCLUSIONS: In a large kindred identified by a child with LCPD who was found to have the FV mutation, FV heterozygosity was found in 3 generations of previously undiagnosed family members and was associated with venous and arterial thrombosis throughout the kindred. We suggest that FV mutation be studied in children with LCPD facilitate diagnosis and genetic counseling for thrombophilia in their parents, siblings, and other kindred members, and because the proband LCPD child with the FV mutation is at increased risk for other thromboembolic abnormalities as an adult.

LEVEL OF EVIDENCE: 1.