Lubala Toni Kasole, Lumaka Aimé, Kanteng Gray, Mutesa Léon, Mukuku Olivier, Wembonyama Stanislas, Hagerman Randi, Luboya Oscar Numbi, Lukusa Tshilobo Prosper
Division of Dysmorphology & Birth Defects, Department of Pediatrics, University of Lubumbashi, Lubumbashi, Congo.
Faculté de Médecine, Département de Pédiatrie, Université de Kinshasa, Kinshasa, Congo.
Mol Genet Genomic Med. 2018 Apr 6;6(4):526-32. doi: 10.1002/mgg3.398.
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.
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.
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.
This study has identified the highest risk features for patients with Fragile X syndrome that have been used to design a universal clinical checklist.
现有的临床检查表是为评估脆性X综合征阳性风险而制定的，但所纳入的样本量相对较小。因此，我们进行了一项荟萃分析，将研究结果进行统计学汇总，以获取智障患者中脆性X综合征临床预测指标患病率的准确数据，从而帮助卫生专业人员改进对脆性X检测的转诊建议。
所有已发表的针对智障患者进行脆性X综合征细胞遗传学和/或分子筛查的研究均符合荟萃分析的条件。所有纳入脆性X综合征临床检查表试验的患者均符合本综述的条件，不基于种族或年龄进行排除。报告比值比（OR）值及95%置信区间以及克朗巴哈系数α，以评估有无脆性X突变的智障患者临床特征的出现频率，从而确定最具鉴别力的特征。
以下特征与脆性X综合征密切相关：手掌皮肤柔软如天鹅绒且手背皮肤冗余[比值比：16.85（95%置信区间10.4 - 27.3；α：0.97）]、睾丸大[比值比：7.14（95%置信区间5.53 - 9.22；α：0.80）]、耳朵大且突出[比值比：18.62（95%置信区间14.38 - 24.1；α：0.98）]、浅蓝色眼睛[比值比：8.97（95%置信区间4.75 - 16.97；α：0.83）]、智障家族史[比值比：3.43（95%置信区间2.76 - 4.27；α：0.81）]以及类自闭症行为[比值比：3.08（95%置信区间2.48 - 3.83；α：0.77）]、扁平足[比值比：11.53（95%置信区间6.79 - 19.56；α：0.91）]、足底褶痕[比值比：3.74（95%置信区间2.67 - 5.24；α：0.70）]。我们注意到横向掌褶痕[比值比：2.68（95%置信区间1.70 - 4.18；α：0.51）]、长脸[比值比：3.69（95%置信区间2.84 - 4.81；α：0.63）]；掌指关节过度伸展[比值比：2.68（95%置信区间2.15 - 3.34；α：0.57）]与脆性X综合征之间的正相关性较弱。
本研究确定了脆性X综合征患者的最高风险特征，这些特征已被用于设计通用的临床检查表。
