PDF(Pubmed)
Abstract：
Bardet-Biedl Syndrome (BBS) is an autosomal recessive non-motile ciliopathy, caused by mutations in more than twenty genes. Their expression leads to the production of BBSome-building proteins or chaperon-like proteins supporting its structure. The prevalence of the disease is estimated at 1: 140,000 - 160,000 of life births. Its main clinical features are retinal dystrophy, polydactyly, obesity, cognitive impairment, hypogonadism, genitourinary malformations, and kidney disease. BBS is characterized by heterogeneous clinical manifestation and the variable onset of signs and symptoms. We present a case series of eight pediatric patients with BBS (6 boys and 2 girls) observed in one clinical center including two pairs of siblings. The patients\' age varies between 2 to 13 years (average age of diagnosis: 22 months). At presentation kidney disorders were observed in seven patients, polydactyly in six patients\' obesity, and psychomotor development delay in two patients. In two patients with kidney disorders, the genetic tests were ordered at the age of 1 and 6 months due to the presence of symptoms suggesting BBS and having an older sibling with the diagnosis of the syndrome. The mutations in the following genes were confirmed: BBS10, MKKS, BBS7/BBS10, BBS7, BBS9. All described patients developed symptoms related to the urinary system and kidney-function impairment. Other most common symptoms are polydactyly and obesity. In one patient the obesity class 3 was diagnosed with multiple metabolic disorders. In six patients the developmental delay was diagnosed. The retinopathy was observed only in one, the oldest patient. Despite having the same mutations (siblings) or having mutations in the same gene, the phenotypes of the patients are different. We aimed to addresses gaps in understanding BBS by comparing our data and existing literature through a narrative review. This research includes longitudinal data and explores genotype-phenotype correlations of children with BBS. BBS exhibits diverse clinical features and genetic mutations, making diagnosis challenging despite defined criteria. Same mutations can result in different phenotypes. Children with constellations of polydactyly and/or kidney disorders and/or early-onset obesity should be managed towards BBS. Early diagnosis is crucial for effective monitoring and intervention to manage the multisystemic dysfunctions associated with BBS.
摘要：
Bardet-Biedl综合征（BBS）是一种常染色体隐性非运动性纤毛病，由二十多个基因的突变引起的。它们的表达导致产生支持其结构的BBSome构建蛋白或伴侣样蛋白。该疾病的患病率估计为1:140,000-160,000的生命出生。其主要临床特征是视网膜营养不良,多指,肥胖，认知障碍，性腺功能减退,泌尿生殖系统畸形,和肾脏疾病。BBS的特征是临床表现不均匀以及体征和症状的可变发作。我们介绍了在一个临床中心观察到的8名患有BBS的儿科患者（6名男孩和2名女孩）的病例系列，其中包括两对兄弟姐妹。患者年龄在2至13岁之间（平均诊断年龄：22个月）。在7例患者中观察到肾脏疾病，6名肥胖患者多指，两名患者的精神运动发育延迟。在两名患有肾脏疾病的患者中，基因测试是在1个月和6个月时订购的，因为存在提示BBS的症状，并且有一个年长的兄弟姐妹诊断为该综合征。证实了以下基因的突变：BBS10，MKKS，BBS7/BBS10，BBS7，BBS9。所有描述的患者均出现与泌尿系统和肾功能损害有关的症状。其他最常见的症状是多指和肥胖。在一名患者中，3级肥胖被诊断出患有多种代谢紊乱。在六名患者中，诊断出发育迟缓。视网膜病变只在一个人中观察到，最老的病人尽管具有相同的突变（兄弟姐妹）或在相同的基因中具有突变，患者的表型不同。我们旨在通过叙事回顾比较我们的数据和现有文献来解决理解BBS的差距。这项研究包括纵向数据，并探讨了患有BBS的儿童的基因型-表型相关性。BBS表现出不同的临床特征和基因突变，尽管有明确的标准，但诊断仍具有挑战性。相同的突变可以导致不同的表型。患有多指和/或肾脏疾病和/或早发性肥胖的儿童应接受BBS治疗。早期诊断对于有效监测和干预以管理与BBS相关的多系统功能障碍至关重要。
