宫内感染病原体,包括弓形虫病,其他(梅毒,水痘,腮腺炎,细小病毒,和艾滋病毒),风疹,巨细胞病毒,和单纯疱疹(TORCH)在怀孕期间易感个体,导致小头畸形,白质疾病,脑萎缩,和胎儿的钙化.伪TORCH综合征是一个总称,由几个综合症组成,由于不同的遗传改变和致病机制。具有简化的回转和多微回转的带状钙化(BLC-PMG)是这些条件之一,由于OCLN基因的双等位基因突变,位于染色体5q13.2.OCLN基因编码闭合蛋白,一种紧密连接的蛋白质,在内皮中表达。在发育中的大脑中缺乏occludin随后导致异常的血脑屏障,因此免疫细胞介导的组织损伤和皮质畸形。在这里,我们介绍了一位患有进行性小头畸形的儿科患者,痉挛,多药耐药癫痫,PMG和颅内带状钙化,伴有中心性尿崩症和肾功能不全。全外显子组测序揭示了OCLN基因中的纯合子W58Ffs*10(c.173_194del)移码突变。在34例具有明显OCLN突变的BLC-PMG病例中,只有三人有肾脏表现,这是大多数死亡的原因。据我们所知,这是第一例被诊断为患有中枢性尿崩症并对去氨加压素治疗有反应的病例,然而,这种临床改善并不能预防患者的肾功能不全.病人4岁时死于败血症,因此早期诊断,对于BLC-PMG患者,有必要对肾脏受累和感染预防措施进行最佳随访。
Intrauterine infections with the pathogens, including toxoplasmosis, other (syphilis, varicella, mumps, parvovirus, and HIV), rubella, cytomegalovirus, and herpes simplex (TORCH) in susceptible individuals during pregnancy, result in microcephaly, white matter disease, cerebral atrophy, and calcifications in the fetus. Pseudo-TORCH syndrome is an umbrella term, consisting of several syndromes, resultant from different genetic alterations and pathogenetic mechanisms. Band-like calcification with simplified gyration and polymicrogyria (BLC-PMG) is one of these conditions, resultant from biallelic mutations in the OCLN gene, located in the chromosome 5q13.2. OCLN gene encodes occludin, a tight junction protein, which is expressed in the endothelia. The absence of occludin in the developing brain subsequently results in abnormal blood-brain barrier, thus immune-cell mediated tissue damage and cortical malformation. Herein, we present a pediatric patient who had progressive microcephaly, spasticity, multi-drug resistant epilepsy, PMG and intracranial band-type calcifications, accompanied by central diabetes insipidus and renal dysfunction. Whole exome sequencing revealed a homozygote W58Ffs*10 (c.173_194del) frameshift mutation in the OCLN gene. Of 34 BLC-PMG cases with demonstrable OCLN mutations, only three had renal manifestations, which is responsible for the majority of the demises. This is the first
case diagnosed as having central diabetes insipidus and responded to desmopressin treatment to the best of our knowledge, however, this clinical improvement could not prevent the patient from renal dysfunction. The patient deceased at four years of age from sepsis, therefore early diagnosis, optimal follow-up for renal involvement and infection prevention measures are necessary for the patients with BLC-PMG.