Department of Child Neurology, Nishi-Niigata Chuo National Hospital, Niigata, Japan.
Pediatr Neurol. 2013 Nov;49(5):364-7. doi: 10.1016/j.pediatrneurol.2013.05.014. Epub 2013 Aug 2.
Mosaic variegated aneuploidy syndrome (Online Mendelian Inheritance in Man 257300), or premature chromatid separation syndrome, is a rare cancer-prone disorder associated with an autosomal recessive trait related to BUB1B gene mutations. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor, and leukemia reported in several cases. Clinical features also include prenatal-onset growth retardation, microcephaly, mild dysmorphism, feeding difficulty, hypotonia, seizures, and developmental delay.
A boy patient exhibited severe developmental delay, microcephaly, hypotonia, intractable seizures including infantile spasms with hypsarrhythmia at 6 months old, and Dandy-Walker malformation on magnetic resonance imaging. Seizures were refractory to conventional antiepileptics and treatment with adrenocorticotropic hormone. Wilms tumor and an unidentified intraorbital tumor also developed at 22 months old.
Chromosomal analysis showed multiple aneuploid cells, and premature chromatid separation was found in all chromosomes in 59.5% of 119 cells, indicating mosaic variegated aneuploidy syndrome.
The present case report demonstrates that mosaic variegated aneuploidy syndrome can be associated with developmental brain anomalies that lead to early-onset epileptic encephalopathy. Awareness of this disorder is important not only for proper diagnosis but also for genetic counseling of the family.
镶嵌性结构异倍体综合征（Online Mendelian Inheritance in Man 257300），又称过早染色单体分离综合征，是一种罕见的易患癌症的疾病，与常染色体隐性特征相关，与 BUB1B 基因突变有关。恶性肿瘤的风险很高，据报道，有几例病例存在横纹肌肉瘤、肾母细胞瘤和白血病。临床特征还包括产前生长迟缓、小头畸形、轻度畸形、喂养困难、张力减退、癫痫发作和发育迟缓。
一名男婴患者表现为严重的发育迟缓、小头畸形、张力减退、难以控制的癫痫发作，包括婴儿痉挛症伴高度失律，6 个月大时磁共振成像显示 Dandy-Walker 畸形。癫痫发作对常规抗癫痫药物和促肾上腺皮质激素治疗均无反应。22 个月大时还出现了肾母细胞瘤和一个未确定的眼眶内肿瘤。
染色体分析显示存在多个非整倍体细胞，119 个细胞中有 59.5%的细胞中发现所有染色体均存在过早染色单体分离，提示镶嵌性结构异倍体综合征。
本病例报告表明，镶嵌性结构异倍体综合征可能与导致早发性癫痫性脑病的发育性脑异常有关。了解这种疾病不仅对正确诊断很重要，而且对家族的遗传咨询也很重要。
