Fragile X checklists: A meta‐analysis and development of a simplified universal clinical checklist. Issue 4 (6th April 2018)

• Record Type: Journal Article
• Authors: Lubala, Toni Kasole; Lumaka, Aimé; Kanteng, Gray; Mutesa, Léon; Mukuku, Olivier; Wembonyama, Stanislas; Hagerman, Randi; Luboya, Oscar Numbi; Lukusa Tshilobo, Prosper
• Is Part Of: Molecular genetics & genomic medicine. Volume 6:Issue 4(2018)
• Page Start: 526
• Page End: 532
• Publication Date: 2018-04-06
• Subjects: checklists -- clinical features -- fragile X -- meta‐analysis; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.398
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: Clinical checklists available have been developed to assess the risk of a positive Fragile X syndrome but they include relatively small sample sizes. Therefore, we carried out a meta‐analysis that included statistical pooling of study results to obtain accurate figures on the prevalence of clinical predictors of Fragile X syndrome among patients with intellectual disability, thereby helping health professionals to improve their referrals for Fragile X testing. Methods: All published studies consisting of cytogenetic and/or molecular screening for fragile X syndrome among patients with intellectual disability, were eligible for the meta‐analysis. All patients enrolled in clinical checklists trials of Fragile X syndrome were eligible for this review, with no exclusion based on ethnicity or age. Odds ratio values, with 95% confidence intervals as well as Cronbach coefficient alpha, was reported to assess the frequency of clinical characteristics in subjects with intellectual disability with and without the fragile X mutation to determine the most discriminating. Results: The following features were strongly associated with Fragile X syndrome: skin soft and velvety on the palms with redundancy of skin on the dorsum of hand [OR: 16.85 (95% CI 10.4–27.3; α:0.97)], large testes [OR: 7.14 (95% CI 5.53–9.22; α: 0.80)], large and prominent ears [OR: 18.62 (95% CI 14.38–24.1; α: 0.98)], pale blue eyes [OR: 8.97 (95% CI 4.75–16.97; α: 0.83)], family history of intellectual disability [OR: 3.43 (95% CI 2.76–4.27; α: 0.81)] as well as autistic‐like behavior [OR: 3.08 (95% CI 2.48–3.83; α: 0.77)], Flat feet [OR: 11.53 (95% CI 6.79–19.56; α:0.91)], plantar crease [OR: 3.74 (95% CI 2.67–5.24; α: 0.70)]. We noted a weaker positive association between transverse palmar crease [OR: 2.68 (95% CI 1.70–4.18; α: 0.51)], elongated face [OR: 3.69 (95% CI 2.84–4.81; α: 0.63)]; hyperextensible metacarpo‐phalangeal joints [OR: 2.68 (95% CI 2.15–3.34; α: 0.57)] and the Fragile X syndrome. Conclusion: This study has identified the highest risk features for patients with Fragile X syndrome that have been used to design a universal clinical checklist. Abstract : Plantar crease (OR 21.70 [11.65–40.45]), Large testes (OR 20.25 [8.61–47.65]), Skin soft and velvety on the palms with redundancy of skin on the dorsum of hand (OR 14.98 [4.18–53.76]), Large and prominent ears (OR 7.42 [4.35–12.66]), Family history of intellectual disability (OR 6.48 [4.11–10.23]) as well as autistic‐like behavior (OR 5.39 [95% CI: 2.59–11.20]) were strongly associated with the FXS.