THE PREVALENCE OF FRAGILE X SYNDROME IN INDIVIDUALS WITH AUTISM SPECTRUM DISORDER: GENETIC INSIGHTS AND DIAGNOSTIC CHALLENGES

Abstract

Objective: Fragile X Syndrome (FXS) is a complex neurodevel opmental condition characterised by delayed language develop ment, dysmorphic features, and impaired cognitive development. FXS, which results from CGG repeat expansion in the FMR1 gene, is the most commonly identified genetic cause of autism. Accu rate diagnosis of FXS is crucial for effective management and treatment. This study aimed to evaluate the prevalence of FXS in individuals with Autism Spectrum Disorder (ASD). Material and Methods: We conducted a retrospective study involv ing 50 patients. Comprehensive fragment analysis of the FMR1 gene was performed, with repeat sequences classified according to the stringent guidelines established by American College of Medical Genetics and Genomics (ACMG), Clinical Molecular Genetics Society (CMGS) ve European Society of Human Genetics (ESHG). Results: FXS was identified in three individuals (6%) within the study cohort. This finding aligns with previous reports indicating prevalence rates between 2% and 8% among ASD populations, thereby confirming the significance of our results. Conclusion: The overlapping symptoms of FXS and idiopathic autism present diagnostic challenges, highlighting the importance of identifying FXS to implement targeted therapies. Family history is critical in identifying at risk individuals, as FXS can lead to varied manifestations in family members, including ataxia and early menopause. Although this study provides valuable insights, the limited sample size underscores the need for larger scale research. Advanced genetic investigations and comprehensive panels could further aid in identifying additional causes of autism. This study emphasises the significance of genetic testing for FXS in the context of autism, aiming to enhance interventions and provide accurate recurrence risk counseling for families affected by this prevalent condition.

Keywords

• Fragile X Syndrome
• autism spectrum disorder
• FMR1 gene
• fragment analysis

OTİZM SPEKTRUM BOZUKLUĞU OLAN BİREYLERDE FRAGİLE X SENDROMU PREVALANSI: GENETİK BULGULAR VE TANISAL ZORLUKLAR

Abstract

Amaç: Fragile X sendromu (FXS), gecikmiş dil gelişimi, dismorfik özellikler ve zihinsel gelişimin bozulması ile karakterize karmaşık bir nörogelişimsel durumdur. FMR1 genindeki CGG tekrar genişlemesi sonucu ortaya çıkan FXS, otizmin en sık belirlenen genetik nedenidir. FXS’ nin doğru tanısı, etkili yönetim ve tedavi için büyük önem taşımaktadır. Bu çalışma, otizmli bireylerde FXS prevalansını değerlendirmeyi amaçlamaktadır. Gereç ve Yöntemler: Bu çalışmada 50 hasta üzerinde yapılan fragman analizi ile FMR1 genindeki CGG tekrar uzunlukları değerlendirildi. Elde edilen sonuçlar, tekrarlayan bölgelerin American College of Medical Genetics and Genomics (ACMG), Clinical Mole cular Genetics Society (CMGS) ve European Society of Human Genetics (ESHG) kılavuzlarına uygun olarak sınıflandırılmasıyla yorumlandı. Bulgular: Literatürde yer alan destekleyici çalışmalar da FXS ile otizm arasındaki bağlantıyı vurgulamaktadır. Çalışma kohortunda üç bireyde (%6) FXS tespit edilmiştir. Bu bulgu, otizm spektrum bozukluğu popülasyonlarında %2 ile %8 arasında değişen prevalans oranlarını bildiren önceki çalışmalarla uyumlu olup, elde edilen sonuçların önemini doğrulamaktadır. Sonuç: FXS ile idiopatik otizmin örtüşen semptomları tanısal zorluklar yaratmakta olup, hedefe yönelik tedavilerin uygulanabilmesi için FXS’ nin belirlenmesi büyük önem taşımaktadır. Aile öyküsü, risk altındaki bireylerin tanımlanmasında kritik bir rol oynamaktadır. FXS, aile bireylerinde ataksi ve erken menopoz gibi farklı klinik belirtilere yol açabilmektedir. Otizmin genetik etiyolojisinin belirlenmesinde altın standart tekniklerden FMR1 fragman analizi ile FXS ekartasyonu sonrası kapsamlı genetik paneller, otizmin ek nedenlerinin belirlenmesine katkı sağlamaktadır. Bu çalışma, otizm bağlamında FXS için genetik testlerin önemini vurgulamakta, müdahaleleri iyileştirmeyi ve etkilenen ailelere doğru tekrar risk danışmanlığı sağlamayı hedeflemektedir.

Keywords

• Fragile X sendromu
• otizm spektrum bozukluğu
• FMR1 geni
• fragman analizi

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