Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, 80131, Italy.
Eur J Med Genet. 2022 Dec;65(12):104659. doi: 10.1016/j.ejmg.2022.104659. Epub 2022 Nov 2.
Pathogenic variants in CENPJ have been first identified in consanguineous Pakistani families with Hereditary Primary Microcephaly type 6 (MCPH6). In addition to primary microcephaly, the CENPJ-related phenotypic spectrum lately included also distinctive and peculiar 'bird-like' craniofacial dysmorphisms, intrauterine and/or postnatal growth retardation, and moderate to severe intellectual disability (ID). These features are also part of the clinical spectrum of Seckel syndrome (SCKL) a genetically heterogeneous neurodevelopmental condition caused by mutations in different genes involved in cell cycle progression. Among these, CENPJ is responsible for type 4 Seckel syndrome (SCKL4). The literature reports two individuals affected by SCKL4 suffering from seizures and other two individuals with other brain malformations in addition to microcephaly. However, neither epilepsy nor brain malformations are described in detail and genotype-phenotype information remains limited. We describe the first Caucasian affected with SCKL4 and harboring a novel, homozygous mutation in CENPJ. We detail the clinical and neuroradiological findings including structural focal epilepsy and a severe brain malformation (i.e., hydranencephaly) that was never associated with SCKL4 to date.
CENPJ 中的致病性变异首先在有遗传性原发性小头畸形 6 型 (MCPH6) 的巴基斯坦近亲家庭中被发现。除了原发性小头畸形外，CENPJ 相关表型谱最近还包括独特而奇特的“鸟样”颅面畸形、宫内和/或产后生长迟缓以及中度至重度智力残疾 (ID)。这些特征也是 Seckel 综合征 (SCKL) 的临床特征的一部分，这是一种遗传异质性的神经发育障碍，由参与细胞周期进程的不同基因突变引起。其中，CENPJ 负责 4 型 Seckel 综合征 (SCKL4)。文献报道了两名受 SCKL4 影响的个体患有癫痫发作，另有两名个体除了小头畸形外还有其他脑畸形。然而，癫痫发作和脑畸形均未详细描述，基因型-表型信息仍然有限。我们描述了首例受 SCKL4 影响的白种人，并在 CENPJ 中携带一种新的纯合突变。我们详细描述了临床和神经影像学发现，包括结构性局灶性癫痫发作和一种严重的脑畸形（即无脑畸形），迄今为止从未与 SCKL4 相关。
