Department of Child Neurology, NHO Nishiniigata Chuo Hospital, 1-14-1 Masago, Nishi-ku, Niigata 950-2085, Japan.
Department of Pediatrics, Niigata City General Hospital, 463-7 Shumoku, Chuo-ku, Niigata 950-1197, Japan.
Brain Dev. 2021 Mar;43(3):448-453. doi: 10.1016/j.braindev.2020.11.003. Epub 2020 Nov 21.
Pallister-Killian syndrome (PKS) is a rare disorder caused by the mosaic tetrasomy of chromosome 12p, and is characterized by facial dysmorphism, developmental delay, hypotonia and seizures.
We report a patient with PKS showing unique polymicrogyria with calcification. He had delayed development and dysmorphic facial features including frontal bossing, hypertelorism, and high arched palate at 6 months of age. Neuroimaging revealed unilateral polymicrogyria with spot calcifications, which predominantly affected the right perisylvian region. Chromosome G-banding showed the karyotype 46,XY, however, array-based comparative genomic hybridization analysis showed mosaic duplication of chromosome 12p, in which CCND2, which encodes cyclin D2 and is a downstream mediator of PI3K-AKT pathway, is located. Supernumerary chromosome of 12p was detected in 58% of buccal mucosa cells by the interphase fluorescence in situ hybridization analysis using chromosome 12 centromere-specific D12Z3 probe. The diagnosis of PKS was made based on distinctive clinical features of our patient and the results of cytogenetic analyses.
This report is, to our knowledge, the first case of a patient with PKS who clearly demonstrates polymicrogyria colocalized with calcifications, as shown by CT scans and MRI, and suggests that a patient with PKS could show structural brain anomalies with calcification. We assume that somatic mosaicism of tetrasomy could cause asymmetrical polymicrogyria in our patient, and speculate that increased dosages of CCND2 at chromosome 12p might be involved in the abnormal neuronal migration in PKS.
帕利斯特-基利安综合征(PKS)是一种由 12p 染色体四体性嵌合体引起的罕见疾病,其特征为面部畸形、发育迟缓、肌张力减退和癫痫发作。
我们报告了一例 PKS 患者,其表现为独特的伴有钙化的多微小脑回畸形。该患者在 6 个月大时出现发育迟缓以及典型的面部畸形特征,包括额骨突出、远视和高拱形腭。神经影像学显示单侧多微小脑回畸形伴点状钙化,主要影响右侧大脑外侧裂区。染色体 G 显带显示核型为 46,XY,然而,基于阵列的比较基因组杂交分析显示 12p 染色体镶嵌性重复,其中 CCND2 基因(编码细胞周期蛋白 D2,是 PI3K-AKT 通路的下游介质)位于其中。间期荧光原位杂交分析使用染色体 12 着丝粒特异性 D12Z3 探针,在 58%的口腔颊黏膜细胞中检测到额外的 12p 号染色体。根据患者独特的临床特征和细胞遗传学分析结果,诊断为 PKS。
据我们所知,本报告首次报道了一例 PKS 患者,其 CT 扫描和 MRI 明确显示多微小脑回畸形伴有钙化,提示 PKS 患者可能存在伴有钙化的结构性脑异常。我们假设四体性嵌合体的体细胞嵌合可能导致了我们患者的不对称性多微小脑回畸形,并推测 12p 染色体上 CCND2 的剂量增加可能参与了 PKS 中的异常神经元迁移。