Eleven studies with over 53,332 participants (one study did not report the number of participants) were included in the review of practical screening programmes for FXS.
Feasibility and acceptability.
The studies suggested that preconceptual and prenatal screening, case finding and cascade screening are feasible and acceptable by affected families and the general population. The rate of acceptance for preconceptual or prenatal screening in self-referred pregnant carriers in Israel was 89 to 92% (3 studies). A prenatal screening study from Finland found that the acceptance rate was 85%. Another study from Finland reported an acceptance rate of 92% for FXS screening in women undergoing invasive prenatal diagnosis due to advancing age, family history, maternal serum screening, ultrasound finding or other reasons. A cascade screening study from Finland found that 48% of the relatives of patients with FXS accepted carrier screening. An Australian study found that 79% of the parents or guardians of patients attending adult and child institutions for learning difficulties gave consent for screening. A cascade screening study from the Netherlands found a rate of acceptance of 76% for the relatives of patients with FXS, while an American study of screening in patients attending a genetics and IVF institute found the acceptance rate for testing was 21%.
Detection of carriers.
The screening programmes were effective in detecting carriers. In one of the prenatal screening studies from Finland, six carriers were detected; among these, one case of foetal PM was detected, one foetal FM and one foetal mosaicism. In the Finnish cascade screening study, 21 pregnant female carriers were detected; among these, there were 3 cases of foetal PM and 9 cases of foetal FM. The cascade screening programme from the Netherlands found that among 70 female relatives tested, 33 PMs and 11 FMs were identified. In the American study that screened pregnant women attending a genetic and IVF centre, PM was detected in 3 of the 474 women without a family history of learning difficulty; no cases of PM or FM were detected among the 214 women with a family history of learning difficulty. No cases of foetal FM were diagnosed in the three women who were PM carriers. In the American study that included 344 pregnant women with a family history of learning difficulty, two women were diagnosed with FM and four were diagnosed with PM. No cases of foetal FM were diagnosed in the three PM carriers who underwent prenatal diagnosis. This study also found that 10 of the 40 pregnant women who were members of previously identified FXS families were carriers. Two cases of foetal FM were identified in the eight carriers who underwent prenatal diagnosis.
The Australian study found that diagnosis and counselling reduced the birth rate in FXS families by 20%, and 78% of pregnant relatives received prenatal diagnosis. All male FM foetuses and 60% female FM foetuses were terminated. Two of the studies from Israel reported that all foetuses with FM were terminated; the other did not report termination. No affected foetuses were terminated in one of the prenatal screening studies from Finland, while the other prenatal screening study did not report termination. All pregnancies with FM were terminated in the cascade screening study from Finland.
Risk of expansion from PM to FM.
The prenatal studies from Israel found that the probability of expansion from PM to FM in maternal transmission was 4.5 to 15.2%.
The authors stated that a comparison of different screening strategies was not possible.