Department of Pediatrics, Marshfield Clinic, Marshfield, WI.
PreventionGenetics, Marshfield, WI.
J Pediatr. 2019 Jan;204:31-37. doi: 10.1016/j.jpeds.2018.08.068. Epub 2018 Oct 4.
To characterize the diversity and prevalence of thoraco-abdominal abnormalities in Bardet-Biedl syndrome (BBS), a model ciliopathy for understanding the role of cilia in human health.
The Clinical Registry Investigating BBS, a worldwide registry exploring the phenotype and natural history of BBS, was used to conduct the study. Protected health information was obtained by subject or family interview and Health Insurance Portability and Accountability Act-approved release of data including imaging studies and genetic testing. Echocardiography and imaging findings were independently confirmed by 2 cardiologists.
Thoraco-abdominal abnormalities were identified in 6 of 368 (1.6%) subjects with a minimum prevalence of 1 in 60 Clinical Registry Investigating BBS participants. Diverse laterality defects were observed suggesting that the underlying ciliopathy randomly alters embryonic left-right axis orientation. Congenital heart disease, common in heterotaxy, was present in 2 subjects. Additional defects, uncommonly reported in BBS, were observed in the central nervous, genitourinary, gastrointestinal, and musculoskeletal systems in the subjects. No BBS genotype was favored in the cohort. One subject had genetic and clinical phenotype diagnostic of both primary ciliary dyskinesia and BBS.
The variety of thoraco-abdominal abnormalities in BBS suggests the pleiotropic nature of these anomalies is not confined to a single pattern or genotype. Clinicians providing care to individuals with BBS should consider the increased prevalence of thoraco-abdominal anomalies in BBS. Individuals with features suggestive of other ciliopathies, such as primary ciliary dyskinesia, should undergo further evaluation for additional genetic disorders.
ClinicalTrials.gov: NCT02329210.
描述 Bardet-Biedl 综合征（BBS）中胸腹部异常的多样性和流行程度，BBS 是一种研究纤毛在人类健康中的作用的典型纤毛病。
本研究使用了 Bardet-Biedl 综合征临床注册研究（Clinical Registry Investigating BBS），该注册研究旨在探索 BBS 的表型和自然病史。通过对受试者或其家属进行访谈，获得了受保护的健康信息，并经健康保险流通与责任法案（Health Insurance Portability and Accountability Act）批准，获取了包括影像学研究和基因检测在内的数据资料。超声心动图和影像学结果由 2 位心脏病专家独立确认。
在 368 名受试者中发现了 6 例（1.6%）胸腹部异常，BBS 临床注册研究的最低患病率为 1/60。观察到多种不同的侧位缺陷，这表明潜在的纤毛病变会随机改变胚胎左右轴的方向。2 名受试者存在先天性心脏病，这在异构综合征中很常见。在这些受试者中还观察到了中枢神经系统、泌尿生殖系统、胃肠道和骨骼肌肉系统中不常见的其他异常。该队列中没有偏好的 BBS 基因型。1 名受试者具有原发性纤毛运动障碍和 BBS 的基因和临床表型诊断。
BBS 中胸腹部异常的多样性表明这些异常的多效性不仅局限于单一模式或基因型。为 BBS 患者提供治疗的临床医生应考虑到 BBS 中胸腹部异常的高发率。具有原发性纤毛运动障碍等其他纤毛病特征的患者应进一步评估其他遗传疾病。
ClinicalTrials.gov：NCT02329210。
