Assessing the Fragile X Syndrome Newborn Screening Landscape

Abstract

Background Fragile X syndrome (FXS) is the most common known inherited form of intellectual disability. Early identification is an important step in linking FXS individuals with appropriate and timely medical and social services. Newborn screening (NBS) is 1 approach that has been used for other conditions to facilitate early identification. Methods A literature review was conducted to identify issues, barriers, challenges, and approaches to addressing challenges related to NBS for FXS. Search terms included: fragile X syndrome, FMR1, newborn screening, screening, and genetic testing. To supplement the literature review, 9 key informant interviews were conducted. Information gathered through these interviews supplemented what was identified in the literature. Information from both the literature review and supplemental interviews was reviewed by 3 researchers who discussed and came to consensus on thematic areas and categorization of issues. Results The barriers and challenges related to NBS for FXS identified in the literature and by experts and stakeholders are categorized into 5 thematic areas: public health burden, treatment, timing, screening/testing methodologies, and translating results. Summaries of these issues and barriers are provided, along with potential approaches to addressing them. Conclusions The issues and barriers described in this article highlight limited areas of knowledge that need be addressed to improve our understanding of FXS and the potential benefit of NBS. The landscape of NBS for FXS could be influenced by a series of research findings over time or a larger breakthrough that demonstrates an effective targeted treatment that has to be implemented early in life.

Inefficient thermogenic mitochondrial respiration due to futile proton leak in a mouse model of fragile X syndrome

“…Because adequate mitochondrial function is essential for synaptic protein translation during plasticity, synaptogenesis may represent, on the one hand, a critical period of vulnerability for FMRP deficient neurons and, on the other hand, a window for therapeutic intervention 6 . Synaptogenesis in the human brain peaks within the first 2 years of life, however, treatment strategies for infants with FXS currently do not exist 83,84 . This is largely because children do not present with signs and symptoms of FXS until about 3‐4 years of life 85 .…”

“…This is largely because children do not present with signs and symptoms of FXS until about 3‐4 years of life 85 . Although there has been a push for the institution of prenatal or newborn screening for the disease, the lack of targeted and effective therapy for infants has served as a major barrier 84 . Thus, development of effective treatments for infants and young children with FXS, such as CoQ 10 , could bolster the case for newborn screening.…”

The Future of Fragile X Syndrome: CDC Stakeholder Meeting Summary

“…More detail on potential research that could provide the evidence needed to assess the feasibility and utility of newborn screening for FXS can be found in a companion article by Riley and Wheeler in this supplement. 18 …”

Repeat expansion and methylation-sensitive triplet-primed polymerase chain reaction for fragile X mental retardation 1 gene screening in institutionalised intellectually disabled individuals

“…The availability of screening will increase earlier identification of individuals at high risk for developmental delay and intellectual disability, as well as avoiding a diagnostic odyssey, as explained in some recent studies. (15)(16)(17) The screening approach using an ID kit removes the need for additional CE with non-expanded samples, hence providing cost savings. The combined approach for this study demonstrated that conservatively, only < 15% of samples needed to be characterised using the conventional method, resulting in cost savings of at least 30%.…”