Prenatal diagnosis for hemophilia A (intron 22 inversion) reveals a rare association with Klinefelter syndrome with diagnostic difficulties in molecular interpretation.

Journal: Blood Coagulation & Fibrinolysis : An International Journal In Haemostasis And Thrombosis

Hemophilia A is an X-linked recessive disorder caused by genetic abnormalities in the F8. Klinefelter syndrome is sex chromosome aneuploidy caused by nondisjunction during meiosis in the germ cells or mitotic cell divisions in the early embryonic cells. We here report an intriguing case of a prenatal diagnosis where a rare association of hemophilia A and Klinefelter syndrome was found in a fetus. This case highlights the diagnostic difficulty where the inverse-PCR for intron 22 inversion defect leading to hemophilia A did not amplify. Indirect molecular testing was done using multiallelic extragenic variable number tandem repeat (VNTR) DXS52 (St14) and polymorphic markers. The interpretation was further complicated by the presence of Klinefelter syndrome. This case highlights the challenges faced when such rare combinations are found during prenatal diagnosis.