De Lange Syndrome: Report of 20 Cases

Typus Degenerativus Amstelodamensis or Amsterdam dwarfism, a syndrome of unknown etiology characterized by mental retardation, a distinctive face, characteristic hands and feet, defective growth and other minor malformations, was first described by Cornelia de Lange in 1933. Approximately 69 cases, including nine autopsies, have been reported in the literature. In this paper we present a further 20, with illustrations of the syndrome from infancy to puberty (including de Lange''s original three cases). The historical, physical, laboratory and radiographic findings of de Lange''s three patients and our 20 are tabulated. Autopsy findings in one of our patients are reported and the literature is briefly reviewed.Although some observers have recently reported chromosome abnormalities in de Lange''s syndrome, we feel that the diagnosis is made from the history and physical examination and that there are no definitive laboratory aids which can confirm the diagnosis. Chromosome studies in all 20 of our patients were normal and the genetic implications are discussed.     

Phocomelia: Report of Three Cases

Three infants were born with phocomelia in Winnipeg during the period from May 1961 to May 1962. In one case thalidomide had been administered to the mother early in the pregnancy. No etiological agent was discovered in the other two, both of whom died. Known teratogenic agents capable of causing phocomelia are reviewed, but no clear association with the two cases described in this report is evident.     

大前庭导水管综合征11例报告

目的:分析大前庭导水管综合征的临床特点及其预防和治疗。方法:应用听力学检查包括纯音听力、儿童游戏测听、声阻抗、听觉脑干诱发电位(Auditory brainstem responses)、40Hz听觉相关电位、耳声发射、多频稳态和影像学检查(CT和／或MRI检查),对11例病例进行分析。结果:全部为感音神经性聋,其中中重度聋为18％,重度聋为55％,极重度聋为27％。听力曲线高频下降型63％,平坦型23％,岛状听力14％。5例有进行性听力下降或突发性听力下降,2例行前庭功能检查,显示前庭功能低下。高分辩内耳CT检查,均为单纯前庭导水管扩大。结论:认为该病为胚胎发育性疾病,其发生与胚胎早期内淋巴管发育障碍有关,感染和头部震荡是该病发生的主要诱因。该病目前尚无确切有效的治疗方法,对有残余听力的聋儿应尽早选配助听器进行听觉、语言训练,可取得较为满意的效果,而听力损失极重,助听器无法达到有效补偿者,或渐进性听力下降至极重度聋者,可选择电子耳蜗植入。     

Cornelia de Lange Syndrome: NIPBL haploinsufficiency downregulates canonical Wnt pathway in zebrafish embryos and patients fibroblasts

Cornelia de Lange Syndrome is a severe genetic disorder characterized by malformations affecting multiple systems, with a common feature of severe mental retardation. Genetic variants within four genes (NIPBL (Nipped-B-like), SMC1A, SMC3, and HDAC8) are believed to be responsible for the majority of cases; all these genes encode proteins that are part of the ‘cohesin complex''. Cohesins exhibit two temporally separated major roles in cells: one controlling the cell cycle and the other involved in regulating the gene expression. The present study focuses on the role of the zebrafish nipblb paralog during neural development, examining its expression in the central nervous system, and analyzing the consequences of nipblb loss of function. Neural development was impaired by the knockdown of nipblb in zebrafish. nipblb-loss-of-function embryos presented with increased apoptosis in the developing neural tissues, downregulation of canonical Wnt pathway genes, and subsequent decreased Cyclin D1 (Ccnd1) levels. Importantly, the same pattern of canonical WNT pathway and CCND1 downregulation was observed in NIPBL-mutated patient-specific fibroblasts. Finally, chemical activation of the pathway in nipblb-loss-of-function embryos rescued the adverse phenotype and restored the physiological levels of cell death.