Kruszka Paul, Porras Antonio R, Addissie Yonit A, Moresco Angélica, Medrano Sofia, Mok Gary T K, Leung Gordon K C, Tekendo-Ngongang Cedrik, Uwineza Annette, Thong Meow-Keong, Muthukumarasamy Premala, Honey Engela, Ekure Ekanem N, Sokunbi Ogochukwu J, Kalu Nnenna, Jones Kelly L, Kaplan Julie D, Abdul-Rahman Omar A, Vincent Lisa M, Love Amber, Belhassan Khadija, Ouldim Karim, El Bouchikhi Ihssane, Shukla Anju, Girisha Katta M, Patil Siddaramappa J, Sirisena Nirmala D, Dissanayake Vajira H W, Paththinige C Sampath, Mishra Rupesh, Klein-Zighelboim Eva, Gallardo Jugo Bertha E, Chávez Pastor Miguel, Abarca-Barriga Hugo H, Skinner Steven A, Prijoles Eloise J, Badoe Eben, Gill Ashleigh D, Shotelersuk Vorasuk, Smpokou Patroula, Kisling Monisha S, Ferreira Carlos R, Mutesa Leon, Megarbane Andre, Kline Antonie D, Kimball Amy, Okello Emmy, Lwabi Peter, Aliku Twalib, Tenywa Emmanuel, Boonchooduang Nonglak, Tanpaiboon Pranoot, Richieri-Costa Antonio, Wonkam Ambroise, Chung Brian H Y, Stevenson Roger E, Summar Marshall, Mandal Kausik, Phadke Shubha R, Obregon María G, Linguraru Marius G, Muenke Maximilian
Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland.
Children's National Health System, Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, District of Columbia.
Am J Med Genet A. 2017 Sep;173(9):2323-2334. doi: 10.1002/ajmg.a.38362. Epub 2017 Jul 27.
Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%. Individuals were grouped into categories of African descent (African), Asian, Latin American, and additional/other. Across these different population groups, NS was phenotypically similar with only 2 of 21 clinical elements showing a statistically significant difference. The most common clinical characteristics found in all population groups included widely spaced eyes and low-set ears in 80% or greater of participants, short stature in more than 70%, and pulmonary stenosis in roughly half of study individuals. Using facial analysis technology, we compared 161 Caucasian, African, Asian, and Latin American individuals with NS with 161 gender and age matched controls and found that sensitivity was equal to or greater than 94% for all groups, and specificity was equal to or greater than 90%. In summary, we present consistent clinical findings from global populations with NS and additionally demonstrate how facial analysis technology can support clinicians in making accurate NS diagnoses. This work will assist in earlier detection and in increasing recognition of NS throughout the world.
努南综合征（NS）是一种常见的遗传综合征，与Ras/丝裂原活化蛋白激酶（MAPK）信号通路基因的功能获得性变异有关。NS的表型在欧洲血统人群中已有充分描述，而对其他群体的关注较少。在本研究中，我们对来自不同人群的NS患者进行了临床评估和面部分析技术检测。我们从20个国家收集了125例NS患者的临床数据和图像，患者平均年龄为8岁，女性占46%。患者被分为非洲裔（非洲人）、亚洲、拉丁美洲以及其他类别。在这些不同人群组中，NS的表型相似，21项临床特征中只有2项存在统计学显著差异。所有人群组中最常见的临床特征包括：80%及以上的参与者眼距宽、耳位低，超过70%的人身材矮小，约一半的研究对象有肺动脉狭窄。使用面部分析技术，我们将161例患有NS的高加索人、非洲人、亚洲人和拉丁美洲人与161例年龄和性别匹配的对照进行比较，发现所有组的敏感性均等于或大于94%，特异性均等于或大于90%。总之，我们展示了来自全球NS患者群体的一致临床发现，并进一步证明了面部分析技术如何能够帮助临床医生准确诊断NS。这项工作将有助于在全球范围内更早地检测和提高对NS的认识。
