Fragile X syndrome: genetic and clinical profile in the Hong Kong Chinese population

Abstract

<p>Introduction: 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. Methods: 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 FMR1 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. Results: 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. Conclusion: 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.</p>

引言：脆性X綜合症是導致遺傳性智力障礙的常見原因之一。就整體發展遲緩和智力障礙而言，脆性X綜合症檢測是第一線基因檢測的一部分。本回顧性研究旨在評估脆性X綜合症檢測的診斷效益及本港華人患者的臨床特徵。 方法：於1993至2022年間共有7291名患者因神經發展相關疾病（如發展遲緩、自閉症譜系障礙及智力障礙）被轉介至醫學遺傳科進行脆性X綜合症檢測。當中103位來自61個家庭的患者帶有FMR1基因全突變，包括59位先證者及44位家族成員。此研究分析了70位患有脆性X綜合症的華人患者的臨床特徵，包括生長、神經行為特徵及其他共病情況。 結果：脆性X綜合症檢測的診斷陽性率為0.8%。先證者的中位確診年齡為4.1歲，而近年的確診年齡有提早趨勢。在2 7個家庭中（44.2%），有多位成員帶有全突變。11%家庭曾進行產前診斷。所有男性患者均有發展遲緩，而女性則為45.0%；86.0%男性患有智力障礙，而只有30.0%女性患者受到影響。常見共病包括肥胖、自閉症譜系障礙、專注力不足／過度活躍症、癲癇、腸胃問題及睡眠障礙。斜視、脊柱側彎及二尖瓣脫垂等情況則較為少見。 結論：脆性X綜合症不僅是純粹的神經發展障礙。我們的研究結果帶出早期診斷與後續管理的重要性，並喚起對相關監測與治療指引的認知。