目的:描述一个经分子证实的Cohen综合征队列的临床表现和长期临床特征。
方法:本研究纳入了来自8个家庭的12名年龄在0.2-13.9岁的科恩综合征患者,中位随访时间为7年。通过VPS13B和全外显子组测序分析进行遗传分析。
结果:双等位基因VPS13B变体,包括3个废话,1个移码,和1个剪接位点变体,并检测到多外显子缺失。普拉德-威利综合征样特征,如张力减退,小手,圆圆的脸,丰满的脸颊,杏仁状的眼睛,在所有婴儿患者中均观察到小颌畸形。从4岁开始,人们注意到脸逐渐拉长并变成椭圆形。科恩综合症的典型面部特征,如长脸,喙状的鼻子,在9岁时,明显的上中央切牙的张开嘴外观变得明显。科恩综合征的其他特征包括视网膜病变(11/11),中性粒细胞减少症(11/12),躯干肥胖(5/12),和近视(5/11)的平均年龄分别为7.8、7、7.5和5岁,分别。11名年龄在5岁以上的患者在最后一次检查中有严重的言语延迟。
结论:应将婴儿期的科恩综合征与Prader-Willi综合征进行鉴别诊断,科恩综合症的典型面部特征在9岁时很突出,当视网膜病变时,中性粒细胞减少症,躯干肥胖变得很明显。此外,应考虑将严重的语音延迟添加到诊断标准中.
To describe the clinical presentation and long-term clinical features of a molecularly confirmed cohort with Cohen syndrome.
Twelve patients with Cohen syndrome aged 0.2-13.9 years from 8 families with a median follow-up of 7 years were enrolled to the study. Genetic analyses were made by VPS13B and whole-exome sequencing analyses.
Biallelic VPS13B variants, including 3 nonsense, 1 frameshift, and 1 splice-site variant, and a multiexon deletion were detected. Prader-Willi syndrome-like features such as hypotonia, small hands, round face with full cheeks, almond-shaped eyes, and micrognathia were observed in all infantile patients. Beginning from age 4 years, it was noticed that the face gradually elongated and became oval. The typical facial features of Cohen syndrome such as a long face, beak-shaped nose, and open-mouth appearance with prominent upper central incisors became evident at age 9. Other Cohen syndrome features including retinopathy (11/11), neutropenia (11/12), truncal obesity (5/12), and myopia (5/11) were detected at the median ages of 7.8, 7, 7.5, and 5 years, respectively. Eleven patients aged older than 5 years at their last examination had severe speech delay.
A differential diagnosis of Cohen syndrome in the infancy should be made with Prader-Willi syndrome, and that the typical facial features for Cohen syndrome is prominent at age 9 years, when retinopathy, neutropenia, and truncal obesity become evident. Moreover, adding the severe speech delay to the diagnostic criteria should be considered.