Hemophilia B in a female with intellectual disability caused by a deletion of Xq26.3q28 encompassing the F9.

BACKGROUND: Hemophilia B is an X-linked recessive disorder caused by mutations in the F9 on Xq27.1. Mainly males are affected but about 20% of female carriers have clotting factor IX activity below 0.40 IU/ml and bleeding problems. Fragile-X syndrome (FMR1) and FRAXE syndrome (AFF2) are well-known causes of X-linked recessive intellectual disability. Simultaneous deletion of both FMR1 and AFF2 in males results in severe intellectual disability. In females the phenotype is more variable. We report a 19-year-old female with severe intellectual disability and a long-standing bleeding history.

METHODS: A SNP array analysis (Illumina Human Cyto 12-SNP genotyping array) and sequencing of F9 were performed. Laboratory tests were performed to evaluate the bleeding diathesis.

RESULTS: Our patient was diagnosed with mild hemophilia B after finding an 11 Mb deletion of Xq26.3q28 that included the following genes among others IDS, SOX3, FMR1, AFF2, and F9.

CONCLUSION: The case history demonstrates that a severe bleeding tendency suggestive of a hemostasis defect in patients with intellectual disability warrants careful hematological and genetic work-up even in the absence of a positive family history.