Report of a Father With Congenital Bilateral Absence of the Vas Deferens Fathering a Child With Beare-Stevenson Syndrome

Background Apert, Pfeiffer, and Crouzon syndromes are autosomal dominant diseases characterized by craniosynostosis. They are paternal age effect disorders. The association between paternal age and Beare-Stevenson syndrome (BSS), a very rare and severe craniosynostosis, is uncertain. Gain-of-function mutations in FGFR2 become progressively enriched in testes as men age and were shown to cause these syndromes. Case report Here, we describe a child affected with BSS, whose father was 36 years old and had congenital bilateral absence of the vas deferens (CBAVD). The child was heterozygous for the pathogenic FGFR2 variant c.1124A > G p.Tyr375Cys. By reviewing the literature, we found that BSS fathers are older than BSS mothers (mean age in years: 39 +/- 10 vs 30 +/- 6, p = 0.006). Male age greater than 34 years and CBAVD are both factors associated with poor spermogram parameters, which may represent an additional selective pressure to sperm carrying FGFR2 gain-of-function mutations. Conclusion These findings are consistent with the hypothesis that BSS is a paternal-origin genetic disorder. Further experimental studies would be needed to confirm this hypothesis.