To Test or NOT to Test? Fragile X Premutation Analysis in Minors- Ethical and Medical Dilemmas and Considerations

Poster Presentation
Friday, May 11, 2018: 5:30 PM-7:00 PM
Hall Grote Zaal (de Doelen ICC Rotterdam)
L. V. Gabis1 and A. Raas-Rothschild2, (1)Pediatrics, Sheba Medical Center, Rehovot, ISRAEL, (2)Genetics, Sheba Medical center, Ramat Gan, Israel
Background: Since 2013, Fragile X screening test has been included in Israeli general screening performed in healthy women above age eighteen. Since then new knowledge emerge on the point that women with premutation beyond the risk of childbearing an offspring with full mutation might face medical and emotional challenges during their life. It has become common knowledge that women with premutation face medical and emotional challenges during their life, beyond the risk of childbearing an offspring with full mutation. Fragile X-associated primary ovarian insufficiency (FXPOI) is a primary cause of infertility and occasionally it may present at a young age, sometimes before the age of family planning. In addition, it seems that a phenotype of learning disabilities, neuropsychiatric issues, ADHD and endocrine dysfunction emerges as a continuum in patients with expansion mutation between the range of premutation and full mutation, both in male and female premutation carriers, as well as social communication awkwardness, possibly autism spectrum features and FXTAS in aging carriers.

Knowledge in regards to the Fragile X status of a child or a teenager might be actionable for the primary care physician and may influence parental attitudes. Minors in families at risk could be tested to benefice from more focused treatment of related impairments- such as learning disabilities, ADHD, ASD or other neuropsychiatric difficulties. On the other hand, physicians may have concerns that carrying a genetic disorder may have a negative impact in terms of emotional burden, social and insurance implications.

Objectives: Main aim was to assess Israeli medical personnel's attitudes in regards to testing Fragile X premutation status in minors. As a secondary aim we probed the knowledge in regards to premutation symptoms. A third aim was to promote knowledge and awareness.

Methods: We used an on- line 10 questions query (SurveyMonkey), including anonymous background information, knowledge and experience with Fragile X families and attitudes towards testing minors.

Results: To date 78 practitioners completed the study of which more than a half had more than twenty years in practice and 20% cared for 5-10 families with Fragile X and 18% for more than ten. 82% of practitioners answered that they would consider testing Fragile X in minors and 13% would test in girls only. In regards to the symptom list, more than 20% confused between symptoms related to permutation and full mutation, mainly in regards to fertility, intellectual impairment, autism and dysmorphic features.


The permutation phenotype is not well recognized. However, most practitioners would test in minors, mainly if full mutation phenotype is present.

We suggest to individualize the decision in regards to testing carrier status in minors sibblings of affected children and to discuss the different options with the parents, while differentiating between general screening for non specific phenotype such as anxiety or ADHD, to permutation carriers with a family member with Fragile X Syndrome. Awareness of the risks and incidence of the various possible manifestations linked to the permutation status are mandatory for advising patients and their families.

See more of: Genetics
See more of: Genetics