Aleo Sebastiano, Cinnante Claudia, Avignone Sabrina, Prada Elisabetta, Scuvera Giulietta, Ajmone Paola Francesca, Selicorni Angelo, Costantino Maria Antonella, Triulzi Fabio, Marchisio Paola, Gervasini Cristina, Milani Donatella
Pediatric Highly Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neuroradiology Unit, Università degli Studi di Milano, Milan, Italy.
Front Cell Dev Biol. 2020 Aug 4;8:710. doi: 10.3389/fcell.2020.00710. eCollection 2020.
Usually overlooked by physicians, olfactory abnormalities are not uncommon. Olfactory malformations have recently been reported in an emerging group of genetic disorders called Mendelian Disorders of the Epigenetic Machinery (MDEM). This study aims to determine the prevalence of olfactory malformations in a heterogeneous group of subjects with MDEM. We reviewed the clinical data of 35 patients, 20 females and 15 males, with a mean age of 9.52 years (SD 4.99). All patients had a MDEM and an already available high-resolution brain MRI scan. Two experienced neuroradiologists reviewed the MR images, noting abnormalities and classifying olfactory malformations. Main findings included Corpus Callosum, Cerebellar vermis, and olfactory defects. The latter were found in 11/35 cases (31.4%), of which 7/11 had Rubinstein-Taybi syndrome (RSTS), 2/11 had CHARGE syndrome, 1/11 had Kleefstra syndrome (KLFS), and 1/11 had Weaver syndrome (WVS). The irregularities mainly concerned the olfactory bulbs and were bilateral in 9/11 patients. With over 30% of our sample having an olfactory malformation, this study reveals a possible new diagnostic marker for MDEM and links the epigenetic machinery to the development of the olfactory bulbs.
嗅觉异常通常被医生忽视，但并不罕见。最近在一组称为表观遗传机制孟德尔疾病（MDEM）的新兴遗传疾病中报告了嗅觉畸形。本研究旨在确定患有MDEM的异质受试者群体中嗅觉畸形的患病率。我们回顾了35例患者的临床资料，其中女性20例，男性15例，平均年龄9.52岁（标准差4.99）。所有患者均患有MDEM且已有高分辨率脑部MRI扫描。两名经验丰富的神经放射科医生对MR图像进行了检查，记录异常情况并对嗅觉畸形进行分类。主要发现包括胼胝体、小脑蚓部和嗅觉缺陷。后者在11/35例（31.4%）中被发现，其中7/11患有鲁宾斯坦-泰比综合征（RSTS），2/11患有CHARGE综合征，1/11患有克莱夫斯特拉综合征（KLFS），1/11患有韦弗综合征（WVS）。异常主要涉及嗅球，9/11的患者为双侧异常。我们样本中超过30%的人存在嗅觉畸形，这项研究揭示了一种可能的MDEM新诊断标志物，并将表观遗传机制与嗅球的发育联系起来。
