ABSTRACT

Purpose

Bardet-Biedl syndrome (BBS) is rare in the Philippines and only limited information on the prevalent subtypes is available as yet. The purpose of this study is to present the clinical characteristics of two Filipino siblings presenting with mutations in BBS5.

Patients and Methods

The Filipino female siblings, aged 11 and 14 years underwent comprehensive ophthalmologic evaluation. Fundus photography, macular optical coherence tomography (OCT) and electroretinography (ERG) were also obtained. Systemic workup was performed including radiographic imaging of limb defects, renal ultrasound, blood chemistry, and transvaginal ultrasound. Targeted Bardet-Biedl sequence analysis and deletion/duplication analysis were performed to determine potential pathogenic mutations.

Results

Both children had poor visual acuity with a myopic refraction. There was a pigmentary retinopathy with retinal pigment epithelium changes and attenuation of vessels without waxy disc pallor. Generalized macular thinning and undetectable ERG responses were recorded. Physical examination revealed obesity, facial anomalies, brachydactyly, postaxial polydactyly, and clinodactyly of fifth digits. Both patients displayed cognitive developmental delay and hypogonadism. Molecular analysis revealed novel compound heterozygous mutations in BBS5 with c.143–1 G > A (splice acceptor) and c.925_931del (p.Gln309ilefs*14), each inherited from one asymptomatic parent.

Conclusion

These are probably the first reported BBS5 mutations causing Bardet-Biedl syndrome in the Philippines. Patients were managed by a multi-disciplinary team and the parents were counseled regarding the prognosis and additional complications associated with the syndrome.

中文翻译：

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具有Bardet-Biedl综合征（BBS）的菲律宾兄弟姐妹中的新型复合杂合病原性BBS5变体。

摘要

目的

在菲律宾，Bardet-Biedl综合征（BBS）很少见，关于流行亚型的信息还很少。这项研究的目的是介绍两个BBS5突变的菲律宾兄弟姐妹的临床特征。

患者和方法

菲律宾女同胞分别为11岁和14岁，接受了全面的眼科评估。还获得了眼底照相，黄斑光学相干断层扫描（OCT）和视网膜电图（ERG）。进行了全身检查，包括肢体缺损的放射照相成像，肾脏超声，血液化学和经阴道超声。进行有针对性的Bardet-Biedl序列分析和缺失/重复分析，以确定潜在的致病突变。

结果

两个孩子的视力都较弱，并伴有近视屈光。出现色素性视网膜病变，视网膜色素上皮发生改变，血管变薄，无蜡状盘面苍白。记录了广泛的黄斑变薄和无法检测到的ERG反应。体格检查发现肥胖，面部畸形，近距离畸形，后轴多指和斜指有五位数。两名患者均表现出认知发育延迟和性腺功能减退。分子分析显示BBS5中新的化合物杂合突变，其c.143-1G> A（剪接受体）和c.925_931del（p.Gln309ilefs * 14），均从一个无症状亲本继承。

结论

这些可能是在菲律宾首次报道的引起Bardet-Biedl综合征的BBS5突变。患者由多学科团队管理，并为父母提供有关该综合征的预后和其他并发症的咨询服务。