Annarita Tagliaferri

Introduction Haemophilias are X‐linked inherited bleeding disorders, due to de novo F8/F9 gene variants in 30–50% of cases. The identification of causative variant in index cases (IC) is crucial for genetic counselling in related women. Over the last 20 years the Emilia‐Romagna Regional Haemophilia Registry documented high proportions of sporadic severe haemophilia. Aim To clarify if carriers’ reproductive choices influence the sporadic/familial ratio of severe haemophilia. Methods Genetic counselling and genotyping in 221 relatives of severe IC were retrospectively reviewed, retrieving reproductive choices and pregnancy history of childbearing‐age carriers from familial and sporadic pedigrees and according to the IC degree of relationship (mothers, daughters, II/other). Results Carriers’ identification rates were lower in sporadic women and in other‐degree relatives. Among childbearing age women (n = 140), carriers were 37/48 (77%) and 57/92 (62%) of familial and sporadic relatives, respectively. Forty‐five/57 sporadic carriers experienced 67 pregnancies, while 21/37 familial carriers had 39 pregnancies (four voluntary terminations), with a significantly higher number of affected sons in the former (40/67 vs. 12/35, P = .025). Prenatal diagnosis was chosen by 40% and 47% of sporadic and familial aware carriers, respectively. Sporadic mothers often avoided further pregnancies (17/38, 45%) after a firstborn affected child, while familial mothers tended to face pregnancies without prenatal approaches (6/10, 60%). Conclusion In this cohort sporadic offspring account for more than 70% of severe haemophilia cases. This increasing proportion is likely to reflect the influence in reproductive choices of awareness of carriers’ status, particularly in sporadic mothers, and of prenatal diagnosis options.