Au C W M, Luk H M, Ho S, Cheng S W, Lam S T S, Chung B H Y, Chong S C, Lo I F M
Department of Clinical Genetics, Hong Kong Children's Hospital, Hong Kong SAR, China.
Clinical Genetics Service, The Hong Kong Sanatorium & Hospital, Hong Kong SAR, China.
Hong Kong Med J. 2025 Jun;31(3):199-207. doi: 10.12809/hkmj2411942. Epub 2025 Jun 5.
Fragile X syndrome (FXS) is a common inherited cause of intellectual disability, and FXS testing is recommended as a first-line genetic investigation for global developmental delay or intellectual disability. This retrospective study evaluated the diagnostic yield of FXS testing and clinical features in Chinese patients in Hong Kong.
From 1993 to 2022, 7291 patients referred to the Clinical Genetic Service for neurodevelopmental conditions (eg, developmental delay, autism spectrum disorder, and intellectual disability) underwent FXS testing. In total, 103 individuals from 61 families were confirmed to have an full mutation, including 59 index cases and 44 family members. Clinical features of 70 Chinese patients with FXS, including growth, neurobehavioural features, and other co-morbidities, were evaluated.
The diagnostic yield of FXS testing was 0.8%. The median age at diagnosis for index cases was 4.1 years, with a trend towards earlier diagnosis in recent years. In 27 families (44.2%), multiple members carried a full mutation. Prenatal diagnosis was arranged in 11% of families. Developmental delay was observed in all males, compared with 45.0% of females. Intellectual disability affected 86.0% of males but only 30.0% of females. Common co-morbidities included obesity, autism spectrum disorder, attention-deficit/hyperactivity disorder, epilepsy, gastrointestinal problems, and sleep disturbances. Features such as strabismus, scoliosis, and mitral valve prolapse were rarely reported.
Fragile X syndrome is more than a pure neurodevelopmental disorder. Our findings highlight the importance of early diagnosis and subsequent management, with awareness of relevant surveillance and management guidelines.
脆性X综合征（FXS）是智力障碍常见的遗传性病因，对于全球发育迟缓或智力障碍患者，建议将FXS检测作为一线基因检查方法。本回顾性研究评估了香港中国患者中FXS检测的诊断率及临床特征。
1993年至2022年期间，7291名因神经发育疾病（如发育迟缓、自闭症谱系障碍和智力障碍）转诊至临床遗传服务机构的患者接受了FXS检测。共有来自61个家庭的103人被确诊存在完全突变，其中包括59名索引病例和44名家庭成员。对70例患有FXS的中国患者的临床特征进行了评估，包括生长发育、神经行为特征和其他合并症。
FXS检测的诊断率为0.8%。索引病例的诊断中位年龄为4.1岁，近年来有早期诊断的趋势。在27个家庭（44.2%）中，多名家庭成员携带完全突变。11%的家庭安排了产前诊断。所有男性均观察到发育迟缓，而女性为45.0%。智力障碍影响了86.0%的男性，但仅30.0%的女性。常见的合并症包括肥胖、自闭症谱系障碍、注意力缺陷多动障碍、癫痫、胃肠道问题和睡眠障碍。斜视、脊柱侧弯和二尖瓣脱垂等特征很少被报告。
脆性X综合征不仅仅是一种单纯的神经发育障碍。我们的研究结果强调了早期诊断及后续管理的重要性，同时需了解相关的监测和管理指南。
