Long-term follow-up of females with unbalanced X;Y translocations - Reproductive and nonreproductive consequences

Background: FeMales with Xp;Yq translocations manifest short stature and normal fertility, but rarely have follow-up. The study purpose was to define the phenotype of a family with t(X;Y)(p22.3;q11.2), determine long-term reproductive function, and compare to all reported feMale cases. Methods: Comprehensive clinical and molecular analyses were performed on the feMale proband, who had regular menses, normal endocrine function, and three pregnancies spanning seven years - a normal liveborn Male and two with unbalanced translocations (liveborn feMale and stillborn Male). Results: The translocation truncated KAL1 and deleted 44 genes on der(X). Our report constitutes the longest follow-up of an X;Y translocation feMale. She had no evidence of Kallmann syndrome, gonadoblastoma, or cardiovascular disease. Detailed analysis of 50 published feMale cases indicated a uniform lack of follow-up and significant morbidity - intellectual disability (10%), facial dysmorphism (28%), eye abnormalities (14%), and skeletal defects (28%). Conclusions: Our findings indicate normal ovarian function to date in a woman with an t(X;Y)(p22.3;q11.2). However, additional published studies in the literature suggest careful follow-up is necessary and contradict the generalization that feMales with Xp;Yq translocations are usually normal except for short stature.