Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Hôpital d'Enfants, CHU de Dijon, France.
Eur J Hum Genet. 2013 Jul;21(7):736-42. doi: 10.1038/ejhg.2012.251. Epub 2012 Nov 28.
Cohen syndrome (CS) is a rare autosomal recessive condition caused by mutations and/or large rearrangements in the VPS13B gene. CS clinical features, including developmental delay, the typical facial gestalt, chorioretinal dystrophy (CRD) and neutropenia, are well described. CS diagnosis is generally raised after school age, when visual disturbances lead to CRD diagnosis and to VPS13B gene testing. This relatively late diagnosis precludes accurate genetic counselling. The aim of this study was to analyse the evolution of CS facial features in the early period of life, particularly before school age (6 years), to find clues for an earlier diagnosis. Photographs of 17 patients with molecularly confirmed CS were analysed, from birth to preschool age. By comparing their facial phenotype when growing, we show that there are no special facial characteristics before 1 year. However, between 2 and 6 years, CS children already share common facial features such as a short neck, a square face with micrognathia and full cheeks, a hypotonic facial appearance, epicanthic folds, long ears with an everted upper part of the auricle and/or a prominent lobe, a relatively short philtrum, a small and open mouth with downturned corners, a thick lower lip and abnormal eye shapes. These early transient facial features evolve to typical CS facial features with aging. These observations emphasize the importance of ophthalmological tests and neutrophil count in children in preschool age presenting with developmental delay, hypotonia and the facial features we described here, for an earlier CS diagnosis.
科恩综合征（CS）是一种罕见的常染色体隐性遗传病，由 VPS13B 基因突变和/或大片段重排引起。CS 的临床特征包括发育迟缓、典型的面部特征、脉络膜视网膜营养不良（CRD）和中性粒细胞减少，这些特征已得到充分描述。CS 的诊断通常在学龄后提出，此时视觉障碍导致 CRD 的诊断和 VPS13B 基因检测。这种相对较晚的诊断排除了准确的遗传咨询。本研究的目的是分析 CS 面部特征在生命早期（6 岁之前）的演变，特别是在学龄前期，以寻找更早诊断的线索。分析了 17 名经分子证实的 CS 患者的照片，从出生到学龄前。通过比较他们在生长过程中的面部表型，我们发现 1 岁前没有特殊的面部特征。然而，在 2 岁至 6 岁之间，CS 儿童已经具有共同的面部特征，如短颈、方形脸伴小下颌和饱满的脸颊、低张力面容、内眦赘皮、长耳伴耳廓上部向外翻和/或耳垂突出、相对较短的人中、小而张开的口伴有口角下垂、厚下唇和异常的眼睛形状。这些早期的短暂面部特征随着年龄的增长逐渐发展为典型的 CS 面部特征。这些观察结果强调了在学龄前出现发育迟缓、低张力和我们所描述的这些面部特征的儿童中进行眼科检查和中性粒细胞计数的重要性，以便更早地诊断 CS。
