Stanford University School of Medicine and Lucile Packard Children's Hospital, CA, USA.
Am J Med Genet C Semin Med Genet. 2010 Feb 15;154C(1):120-32. doi: 10.1002/ajmg.c.30238.
Holoprosencephaly (HPE) is a complex congenital brain malformation characterized by failure of the forebrain to bifurcate into two hemispheres, a process normally completed by the fifth week of gestation. Modern high-resolution brain magnetic resonance imaging (MRI) has allowed detailed analysis of the cortical, white matter, and deep gray structural anomalies in HPE in living humans. This has led to better classification of types of HPE, identification of newer subtypes, and understanding of the pathogenesis. Currently, there are four generally accepted subtypes of HPE: alobar, semilobar, lobar, and middle interhemispheric variant. These subtypes are defined primarily by the degree and region of neocortical nonseparation. Rather than there being four discrete subtypes of HPE, we believe that there is a continuum of midline neocortical nonseparation resulting in a spectrum disorder. Many patients with HPE fall within the border zone between the neighboring subtypes. In addition, there are patients with very mild HPE, where the nonseparation is restricted to the preoptic (suprachiasmic) area. In addition to the neocortex, other midline structures such as the thalami, hypothalamic nuclei, and basal ganglia are often nonseparated in HPE. The cortical and subcortical involvements in HPE are thought to occur due to a disruption in the ventral patterning process during development. The severity of the abnormalities in these structures determines the severity of the neurodevelopmental outcome and associated sequelae.
无脑回畸形（HPE）是一种复杂的先天性脑畸形，其特征是前脑未能分裂成两个半球，这一过程通常在妊娠第 5 周完成。现代高分辨率脑磁共振成像（MRI）使人们能够对 HPE 患者大脑皮质、白质和深部灰质结构异常进行详细分析。这导致了更好的 HPE 分型，识别了新的亚型，并加深了对发病机制的理解。目前，公认的 HPE 有四种亚型：全前脑、半叶脑、部分侧脑室脑和中间脑半球间变异型。这些亚型主要根据新皮质未分离的程度和区域来定义。我们认为，存在从中线新皮质未分离到谱系障碍的连续谱，而不是存在四种离散的 HPE 亚型。许多 HPE 患者处于相邻亚型之间的边界区。此外，还有一些 HPE 患者非常轻微，未分离仅限于视前区（视交叉上核）。除了大脑皮质，丘脑、下丘脑核和基底节等其他中线结构在 HPE 中通常也未分离。HPE 中皮质和皮质下结构的受累被认为是由于发育过程中腹侧模式形成过程中断所致。这些结构的异常严重程度决定了神经发育结局和相关后遗症的严重程度。
