Wieck Gretchen, Leventer Richard J, Squier Waney M, Jansen An, Andermann Eva, Dubeau Francois, Ramazzotti Anna, Guerrini Renzo, Dobyns William B
Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Brain. 2005 Dec;128(Pt 12):2811-21. doi: 10.1093/brain/awh658.
Polymicrogyria (PMG) and periventricular nodular heterotopia (PNH) are two developmental brain malformations that have been described independently in multiple syndromes. Clinically, they present with epilepsy and developmental handicaps in both children and adults. Here we describe their occurrence together as the two major findings in a group of at least three cortical malformation syndromes. We identified 30 patients as having both PNH and PMG on brain imaging, reviewed clinical data and brain imaging studies (or neuropathology summary) for all, and performed mutation analysis of FLNA in nine patients. The group was divided into three subtypes based on brain imaging findings. The frontal-perisylvian PNH-PMG subtype included eight patients (seven males and one female) between 2 days and 10 years of age. It was characterized by PNH lining the lateral body and frontal horns of the lateral ventricles and by PMG most severe in the posterior frontal and perisylvian areas, occasionally with extension to the parietal lobes beyond the immediate perisylvian cortex. The posterior PNH-PMG subtype consisted of 20 patients (15 male and 5 female) between 5 days and 40 years of age. It was characterized by PNH in the trigones, temporal and posterior horns of the lateral ventricles, and PMG most severe in the temporo-parieto-occipital regions. The third type was found in 2 females aged 7 months and 2 years, and was characterized by severe congenital microcephaly and more diffuse cortical abnormality. The PNH-PMG subtypes described here have distinct imaging and clinical phenotypes that suggest multiple genetic aetiologies involving defects in multiple genes, and a shared pathophysiological mechanism for PNH and PMG. The frontal-perisylvian and posterior subtypes both had skewing of the sex ratio towards males, which suggests the possibility of X-linked inheritance. Delineation of these syndromes will also aid in providing more accurate diagnosis and prognostic information for patients with these malformations.
多小脑回畸形（PMG）和室周结节性异位（PNH）是两种发育性脑畸形，在多种综合征中被分别描述。临床上，儿童和成人都会出现癫痫和发育障碍。在此，我们描述它们共同出现的情况，这是一组至少三种皮质畸形综合征的两个主要发现。我们通过脑部成像确定了30例同时患有PNH和PMG的患者，回顾了所有患者的临床数据和脑部成像研究（或神经病理学总结），并对9例患者进行了FLNA基因的突变分析。根据脑部成像结果，该组被分为三个亚型。额颞周PNH-PMG亚型包括8例年龄在2天至10岁之间的患者（7例男性和1例女性）。其特征是PNH沿侧脑室体部和额角排列，PMG在额叶后部和颞周区域最为严重，偶尔延伸至紧邻颞周皮质之外的顶叶。后PNH-PMG亚型由20例年龄在5天至40岁之间的患者（15例男性和5例女性）组成。其特征是PNH位于侧脑室三角区、颞角和后角，PMG在颞顶枕区域最为严重。第三种类型见于2例年龄分别为7个月和2岁的女性，其特征是严重的先天性小头畸形和更弥漫的皮质异常。这里描述的PNH-PMG亚型具有独特的影像学和临床表型，提示涉及多个基因缺陷的多种遗传病因，以及PNH和PMG共同的病理生理机制。额颞周和后亚型的性别比例均偏向男性，这提示存在X连锁遗传的可能性。明确这些综合征也将有助于为患有这些畸形的患者提供更准确的诊断和预后信息。
