Prevalence of Fragile X Syndrome in Georgian Patients with Autism Spectrum Disorder and/or Intellectual Disability: Cross-Sectional Study and Review of Current Approaches

Nazi Tabatadze^1,2,3*Otar Koniashvili^1,3Gia Melikishvili¹Thierry Bienvenu^4,5Laurence Cuisset⁶Flora Tassone^7,8Dragana D. Protic^10,9Nino Naneishvili^11,3Maia Zarandia¹²Sopo Gverdtsiteli¹³Sopio Kakabadze¹⁴Tamar Gachechiladze^1,2Mariam Melikishvili¹Zurab Kuchukashvili¹⁵Tamaz Giunashvili11¹⁵Ketevan Silagava¹⁵Giorgi Mamardashvili^1,3Mariam Chipashvili¹⁶Ketevan Barabadze^17,2Leonard Abbeduto^18,19Randi Jenssen Hagerman^20,21

• ¹department of pediatrics, MediclubGeorgia medical center, Tbilisi, Georgia, Tbilisi, Georgia
• ²Ivane Javakhishvili Tbilisi State University Faculty of Medicine, Tbilisi, Georgia
• ³Tbilisi State Medical University Faculty of Medicine, Tbilisi, Georgia
• ⁴Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, « Genetic vulnerability to addictive and psychiatric disorders, Paris, France
• ⁵Service de médecine génomique des maladies de système et d’organe, Hôpital Cochin, Assistance Publique. Centre Université de Paris Cité,, paris, France
• ⁶Assistance Publique – Hôpitaux de Paris, APHP. Centre Universitaire Paris, Hôpital Cochin, Laboratoire de Génétique et Biologie Moléculaires, Paris, France
• ⁷Department of Biochemistry and Molecular Medicine, University of California Davis, School of Medicine, Sacramento, United States
• ⁸Medical Investigation of Neurodevelopmental Disorders Institute, University of California Davis, Sacramento, United States
• ⁹Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
• ¹⁰Fragile X Clinic, Special Hospital for Cerebral Palsy and Developmental Neurology,, Belgrade, Serbia
• ¹¹Center for Mental Health and Prevention of Addiction, Tbilisi, Georgia
• ¹²Tbilisi State Medical University, Department of Molecular and Medical Genetics,, Tbilisi, Georgia
• ¹³Danish Epilepsy Center, Department of Epilepsy Genetics and Personalized Medicine, Dianalund, Denmark
• ¹⁴Ascension Saint Joseph Hospital, Department of Internal Medicine, Chicago, United States
• ¹⁵Ivane Javakhishvili Tbilisi State University Faculty of Exact and Natural Sciences, Tbilisi, Georgia
• ¹⁶Tbilisi State University, Deprtment of pharmacology, Tbilisi, Georgia
• ¹⁷Tbilisi state Medical University And High Technology Medical Center University Clinic, Tbilisi, Georgia
• ¹⁸MIND Institute, University of California Davis Health System, Sacramento, United States
• ¹⁹Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, United States
• ²⁰University of California Davis MIND Institute, Sacramento, United States
• ²¹Department of Pediatrics, School of Medicine, University of California, Sacramento, United States

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability (ID) and autism spectrum disorder (ASD). Despite its clinical importance, data on FXS prevalence in Georgia remains limited. This study aims to assess the prevalence of FXS in individuals with ID and/or ASD in Georgia and to review current diagnostic and management approaches. A total of 441 patients (n=332 males and n=109 females) diagnosed with ID and/or ASD based on DSM-5 criteria underwent genetic testing for FXS using a PCR-based approach. The FXS full mutation was identified in 25 patients (5.7%), and four individuals were carriers of the premutation. One patient had a large FMR1 deletion, thus the prevalence of the full mutation (FM) was 5.9%, and the prevalence of a premutation was 0.9%. The FXS-positive cohort showed a significant male predominance (80.77%). Among patients with ASD, 1.9% tested positive for FXS, and these individuals displayed more severe behavioral problems, requiring more intensive intervention. Phenotypic features such as a long face (76.9%), joint hypermobility (61.5%), and flat feet (53.8%) were commonly observed. The study underscores a significant diagnostic delay, with the average age of clinical ID/ASD diagnosis at 8.42 years and a lag of 4.63 years before FXS is identified. Compared to the U.S., where FXS diagnosis occurs at 35-41 months, Georgia faces significant barriers, including low awareness, lack of early screening, and limited access to genetic testing. Efforts to address these challenges include public awareness campaigns and integration of early genetic testing protocols.