Fragile X checklists: A meta-analysis and development of a simplified universal clinical checklist

Toni Kasole Lubala; Aimé Lumaka; Gray Kanteng; Léon Mutesa; Olivier Mukuku; Stanislas Wembonyama; Randi Hagerman; Oscar Numbi Luboya; Prosper Lukusa Tshilobo

doi:10.1002/mgg3.398

Fragile X checklists: A meta-analysis and development of a simplified universal clinical checklist

Mol Genet Genomic Med. 2018 Apr 6;6(4):526-532. doi: 10.1002/mgg3.398. Online ahead of print.

Authors

Toni Kasole Lubala¹, Aimé Lumaka^{2

3}, Gray Kanteng¹, Léon Mutesa⁴, Olivier Mukuku⁵, Stanislas Wembonyama¹, Randi Hagerman^{6

7}, Oscar Numbi Luboya¹, Prosper Lukusa Tshilobo^{2

3}

Affiliations

¹ Division of Dysmorphology & Birth Defects, Department of Pediatrics, University of Lubumbashi, Lubumbashi, Congo.
² Faculté de Médecine, Département de Pédiatrie, Université de Kinshasa, Kinshasa, Congo.
³ Centre de Génétique Humaine, Institut National de Recherche Biomédicale, Kinshasa, Congo.
⁴ Center for Human Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda.
⁵ Département de Pédiatrie, Institut Supérieur des Techniques Médicales, Lubumbashi, Congo.
⁶ MIND Institute, University of California Davis, Sacramento, CA, USA.
⁷ Department of Pediatrics, University of California Davis Medical Center, Sacramento, CA, USA.

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.

Keywords: checklists; clinical features; fragile X; meta-analysis.