REFERENCES
1. Hunter J, Rivero-Arias O, Angelov A, Kim E, Fotheringham I, Leal J. Epidemiology of fragile X syndrome: a systematic review and meta-analysis. Am J Med Genet A 2014;164A:1648-58.
2. Saldarriaga W, Forero-Forero JV, González-Teshima LY, et al. Genetic cluster of fragile X syndrome in a Colombian district. J Hum Genet 2018;63:509-16.
3. Bakker CE, de Diego Otero Y, Bontekoe C, et al. Immunocytochemical and biochemical characterization of FMRP, FXR1P, and FXR2P in the mouse. Exp Cell Res 2000;258:162-70.
4. Tassone F, Hagerman RJ, Taylor AK, Gane LW, Godfrey TE, Hagerman PJ. Elevated levels of FMR1 mRNA in carrier males: a new mechanism of involvement in the fragile-X syndrome. Am J Hum Genet 2000;66:6-15.
6. Hagerman RJ, Hagerman P. Fragile X-associated tremor/ataxia syndrome-features, mechanisms and management. Nat Rev Neurol 2016;12:403-12.
7. Hagerman RJ, Protic D, Rajaratnam A, Salcedo-Arellano MJ, Aydin EY, Schneider A. Fragile X-associated neuropsychiatric disorders (FXAND). Front Psychiatry 2018;9:564.
8. Salcedo-Arellano MJ, Hagerman RJ, Martínez-Cerdeño V. Fragile X syndrome: clinical presentation, pathology and treatment. Gac Med Mex 2020;156:60-6.
9. Hagerman RJ, Berry-Kravis E, Hazlett HC, et al. Fragile X syndrome. Nat Rev Dis Primers 2017;3:17065.
10. Richter JD, Zhao X. The molecular biology of FMRP: new insights into fragile X syndrome. Nat Rev Neurosci 2021;22:209-22.
11. Bagni C, Oostra BA. Fragile X syndrome: from protein function to therapy. Am J Med Genet A 2013;161A:2809-21.
12. Huber KM, Gallagher SM, Warren ST, Bear MF. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A 2002;99:7746-50.
13. Berry-Kravis E, Des Portes V, Hagerman R, et al. Mavoglurant in fragile X syndrome: results of two randomized, double-blind, placebo-controlled trials. Sci Transl Med 2016;8:321ra5.
14. Youssef EA, Berry-Kravis E, Czech C, et al. FragXis Study Group. Effect of the mGluR5-NAM basimglurant on behavior in adolescents and adults with fragile X syndrome in a randomized, double-blind, placebo-controlled trial: fragXis phase 2 results. Neuropsychopharmacology 2018;43:503-12.
15. Katona I, Freund TF. Multiple functions of endocannabinoid signaling in the brain. Annu Rev Neurosci 2012;35:529-58.
16. Palumbo JM, Thomas BF, Budimirovic D, et al. Role of the endocannabinoid system in fragile X syndrome: potential mechanisms for benefit from cannabidiol treatment. J Neurodev Disord 2023;15:1.
17. Jung KM, Sepers M, Henstridge CM, et al. Uncoupling of the endocannabinoid signalling complex in a mouse model of fragile X syndrome. Nat Commun 2012;3:1080.
18. Heussler H, Cohen J, Silove N, et al. A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome. J Neurodev Disord 2019;11:16.
19. Ferron L, Nieto-Rostro M, Cassidy JS, Dolphin AC. Fragile X mental retardation protein controls synaptic vesicle exocytosis by modulating N-type calcium channel density. Nat Commun 2014;5:3628.
20. Bausch AE, Ehinger R, Straubinger J, Zerfass P, Nann Y, Lukowski R. Loss of sodium-activated potassium channel slack and FMRP differentially affect social behavior in mice. Neuroscience 2018;384:361-74.
21. Tempio A, Boulksibat A, Bardoni B, Delhaye S. Fragile X syndrome as an interneuronopathy: a lesson for future studies and treatments. Front Neurosci 2023;17:1171895.
22. Paluszkiewicz SM, Olmos-Serrano JL, Corbin JG, Huntsman MM. Impaired inhibitory control of cortical synchronization in fragile X syndrome. J Neurophysiol 2011;106:2264-72.
23. Miller L, Mcintosh D, Mcgrath J, et al. Electrodermal responses to sensory stimuli in individuals with fragile X syndrome: a preliminary report. Am J Med Genet 1999;83:268-79.
24. Cordeiro L, Ballinger E, Hagerman R, Hessl D. Clinical assessment of DSM-IV anxiety disorders in fragile X syndrome: prevalence and characterization. J Neurodev Disord 2011;3:57-67.
25. Khayachi A, Gwizdek C, Poupon G, et al. Sumoylation regulates FMRP-mediated dendritic spine elimination and maturation. Nat Commun 2018;9:757.
26. Janusz A, Milek J, Perycz M, et al. The fragile X mental retardation protein regulates matrix metalloproteinase 9 mRNA at synapses. J Neurosci 2013;33:18234-41.
27. Dziembowska M, Pretto DI, Janusz A, et al. High MMP-9 activity levels in fragile X syndrome are lowered by minocycline. Am J Med Genet A 2013;161A:1897-903.
28. Leigh MJ, Nguyen DV, Mu Y, et al. A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile X syndrome. J Dev Behav Pediatr 2013;34:147-55.
29. Bilousova TV, Dansie L, Ngo M, et al. Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model. J Med Genet 2009;46:94-102.
30. Dansie LE, Phommahaxay K, Okusanya AG, et al. Long-lasting effects of minocycline on behavior in young but not adult Fragile X mice. Neuroscience 2013;246:186-98.
31. Gantois I, Khoutorsky A, Popic J, et al. Metformin ameliorates core deficits in a mouse model of fragile X syndrome. Nat Med 2017;23:674-7.
32. Protic DD, Aishworiya R, Salcedo-Arellano MJ, et al. Fragile X syndrome: from molecular aspect to clinical treatment. Int J Mol Sci 2022;23:1935.
33. Yrigollen CM, Martorell L, Durbin-Johnson B, et al. AGG interruptions and maternal age affect FMR1 CGG repeat allele stability during transmission. J Neurodev Disord 2014;6:24.
34. Nolin SL, Glicksman A, Ersalesi N, et al. Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers. Genet Med 2015;17:358-64.
35. Sullivan AK, Marcus M, Epstein MP, et al. Association of FMR1 repeat size with ovarian dysfunction. Hum Reprod 2005;20:402-12.
36. Rajaratnam A, Shergill J, Salcedo-Arellano M, Saldarriaga W, Duan X, Hagerman R. Fragile X syndrome and fragile X-associated disorders. F1000Res 2017;6:2112.
37. Aishworiya R, Hwang YH, Santos E, et al. Clinical implications of somatic allele expansion in female FMR1 premutation carriers. Sci Rep 2023;13:7050.
38. Harris SW, Hessl D, Goodlin-Jones B, et al. Autism profiles of males with fragile X syndrome. Am J Ment Retard 2008;113:427-38.
39. Budimirovic DB, Protic DD, Delahunty CM, et al. FORWARD Consortium. Sleep problems in fragile X syndrome: cross-sectional analysis of a large clinic-based cohort. Am J Med Genet A 2022;188:1029-39.
40. Vismara LA, McCormick CEB, Shields R, Hessl D. Extending the parent-delivered early start denver model to young children with fragile X syndrome. J Autism Dev Disord 2019;49:1250-66.
41. Chitwood KL, Hess LG, Diez-Juan M, and Braden ML. Chapter 10: academic intervention and therapies for children with FXS. Fragile X syndrome and premutation disorders: new developments and treatments. London: Mac Keith Press; 2020. Available from: https://www.mackeith.co.uk/product/fragile-x-syndrome-and-premutation-disorders-chapter-10-academic-intervention-and-therapies-for-children-with-fxs/ [Last accessed on 6 Sep 2023].
42. Dawson G, Rogers S, Munson J, et al. Randomized, controlled trial of an intervention for toddlers with autism: the early start denver model. Pediatrics 2010;125:e17-23.
43. Vismara LA, Rogers SJ. Behavioral treatments in autism spectrum disorder: what do we know? Annu Rev Clin Psychol 2010;6:447-68.
44. Greiss Hess L, Fitzpatrick SE, Nguyen DV, et al. A randomized, double-blind, placebo-controlled trial of low-dose sertraline in young children with fragile X syndrome. J Dev Behav Pediatr 2016;37:619-28.
45. Eckert EM, Dominick KC, Pedapati EV, et al. Pharmacologic interventions for irritability, aggression, agitation and self-injurious behavior in fragile X syndrome: an initial cross-sectional analysis. J Autism Dev Disord 2019;49:4595-602.
46. Hagerman RJ, Berry-Kravis E, Kaufmann WE, et al. Advances in the treatment of fragile X syndrome. Pediatrics 2009;123:378-90.
47. Moskowitz LJ, Jones EA. Uncovering the evidence for behavioral interventions with individuals with fragile X syndrome: a systematic review. Res Dev Disabil 2015;38:223-41.
48. Amor DJ. Fragile X Syndrome and Premutation Disorders: New Developments and Treatments Edited by Randi J, Hagerman and Paul J, Hagerman. London: Mac Keith Press, 2020. £75.00 (Hardback), pp 176. ISBN: 9781911612377. Develop Med Child Neuro 2021;63:119.
49. Schneider A, Ligsay A, Hagerman RJ. Fragile X syndrome: an aging perspective. Dev Disabil Res Rev 2013;18:68-74.
50. Tassone F, Hagerman RJ, Ikle DN, et al. FMRP expression as a potential prognostic indicator in fragile X syndrome. Am J Med Genet 1999;84:250-61.
51. Loesch DZ, Huggins RM, Hagerman RJ. Phenotypic variation and FMRP levels in fragile X. Ment Retard Dev Disabil Res Rev 2004;10:31-41.
52. de Vries BB, Wiegers AM, Smits AP, et al. Mental status of females with an FMR1 gene full mutation. Am J Hum Genet 1996;58:1025-32.
53. Utari A, Adams E, Berry-Kravis E, et al. Aging in fragile X syndrome. J Neurodev Disord 2010;2:70-6.
54. Kidd SA, Lachiewicz A, Barbouth D, et al. Fragile X syndrome: a review of associated medical problems. Pediatrics 2014;134:995-1005.
55. Berry-Kravis E, Raspa M, Loggin-Hester L, Bishop E, Holiday D, Bailey DB. Seizures in fragile X syndrome: characteristics and comorbid diagnoses. Am J Intellect Dev Disabil 2010;115:461-72.
56. Hagerman RJ, Protic D, Berry-Kravis EM. Chapter 5: medical, psychopharmacological, and targeted treatment for FXS. London: Mac Keith; 2020. Available from: https://www.mackeith.co.uk/product/fragile-x-syndrome-and-premutation-disorders-chapter-5-medical-psychopharmacological-and-targeted-treatment-for-fxs/ [Last accessed on 6 Sep 2023].
57. Ramírez-Cheyne JA, Duque GA, Ayala-Zapata S, et al. Fragile X syndrome and connective tissue dysregulation. Clin Genet 2019;95:262-7.
58. Tassanakijpanich N, Cohen J, Cohen R, Srivatsa UN, Hagerman RJ. Cardiovascular problems in the fragile X premutation. Front Genet 2020;11:586910.
60. Nowicki ST, Tassone F, Ono MY, et al. The Prader-willi phenotype of fragile X syndrome. J Dev Behav Pediatr 2007;28:133-8.
61. Badran HS, Abulnasr KM, Abd El Hameed Nasser S. Effect of recurrent otitis media on language profile in children with fragile X syndrome. Clin Med Insights Ear Nose Throat 2013;6:1-7.
62. Berry-kravis E, Grossman AW, Crnic LS, Greenough WT. Understanding fragile X syndrome. Current Paediatrics 2002;12:316-24.
63. Abbeduto L, Hagerman RJ. Language and communication in fragile X syndrome. Ment Retard Dev Disabil Res Rev 1997;3:313-22.
64. Grigos MI, Hayden D, Eigen J. Perceptual and articulatory changes in speech production following PROMPT treatment. J Med Speech Lang Pathol 2010;18:46-53.
65. Torrioli M, Vernacotola S, Setini C, et al. Treatment with valproic acid ameliorates ADHD symptoms in fragile X syndrome boys. Am J Med Genet A 2010;152A:1420-7.
66. Frigerio A, Montali L, Fine M. Attention deficit/hyperactivity disorder blame game: a study on the positioning of professionals, teachers and parents. Health 2013;17:584-604.
68. Wirojanan J, Jacquemont S, Diaz R, et al. The Efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome. J Clin Sleep Med 2009;5:145-50.
69. Biggio G, Biggio F, Talani G, et al. Melatonin: from neurobiology to treatment. Brain Sci 2021;11:1121.
70. Jacquemont S, Curie A, des Portes V, et al. Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci Transl Med 2011;3:64ra1.
71. Levenga J, Hayashi S, de Vrij FM, et al. AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome. Neurobiol Dis 2011;42:311-7.
73. Berry-Kravis E. Disease-targeted treatment translation in fragile X syndrome as a model for neurodevelopmental disorders. J Child Neurol 2022;37:797-812.
74. Berry-Kravis EM, Hessl D, Rathmell B, et al. Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: a randomized, controlled, phase 2 trial. Sci Transl Med 2012;4:152ra127.
75. Berry-Kravis E, Hagerman R, Visootsak J, et al. Arbaclofen in fragile X syndrome: results of phase 3 trials. J Neurodev Disord 2017;9:3.
76. Sansone SM, Widaman KF, Hall SS, et al. Psychometric study of the aberrant behavior checklist in fragile x syndrome and implications for targeted treatment. J Autism Dev Disord 2012;42:1377-92.
77. Erickson CA, Wink LK, Ray B, et al. Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome. Psychopharmacology (Berl) 2013;228:75-84.
78. Erickson CA, Davenport MH, Schaefer TL, et al. Fragile X targeted pharmacotherapy: lessons learned and future directions. J Neurodev Disord 2017;9:7.
79. Ligsay A, Van Dijck A, Nguyen DV, et al. A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome. J Neurodev Disord 2017;9:26.
80. Budimirovic DB, Dominick KC, Gabis LV, et al. Gaboxadol in fragile X syndrome: a 12-week randomized, double-blind, parallel-group, phase 2a study. Front Pharmacol 2021;12:757825.
81. Berry-Kravis E, Horrigan JP, Tartaglia N, et al. FXS-001 Investigators. A double-blind, randomized, placebo-controlled clinical study of trofinetide in the treatment of fragile X syndrome. Pediatr Neurol 2020;110:30-41.
82. Thurman AJ, Potter LA, Kim K, et al. Controlled trial of lovastatin combined with an open-label treatment of a parent-implemented language intervention in youth with fragile X syndrome. J Neurodev Disord 2020;12:12.
83. Monyak RE, Emerson D, Schoenfeld BP, et al. Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model. Mol Psychiatry 2017;22:1140-8.
84. Wang M, Tong JH, Zhu G, Liang GM, Yan HF, Wang XZ. Metformin for treatment of antipsychotic-induced weight gain: a randomized, placebo-controlled study. Schizophr Res 2012;138:54-7.
85. Dy ABC, Tassone F, Eldeeb M, Salcedo-Arellano MJ, Tartaglia N, Hagerman R. Metformin as targeted treatment in fragile X syndrome. Clin Genet 2018;93:216-22.
86. Biag HMB, Potter LA, Wilkins V, et al. Metformin treatment in young children with fragile X syndrome. Mol Genet Genomic Med 2019;7:e956.
87. Protic D, Aydin EY, Tassone F, Tan MM, Hagerman RJ, Schneider A. Cognitive and behavioral improvement in adults with fragile X syndrome treated with metformin-two cases. Mol Genet Genomic Med 2019;7:e00745.
88. Protic D, Kaluzhny P, Tassone F, Hagerman R. Prepubertal metformin treatment in fragile X syndrome alleviated macroorchidism: a case study. Available from: https://www.semanticscholar.org/paper/Prepubertal-Metformin-Treatment-in-Fragile-X-A-Case-Protic-Kaluzhny/bc72f48893f277b9dc271413fe51e099935fbfb6 [Last accessed on 1 Sep 2023].
89. Carbone E, Manduca A, Cacchione C, Vicari S, Trezza V. Healing autism spectrum disorder with cannabinoids: a neuroinflammatory story. Neurosci Biobehav Rev 2021;121:128-43.
90. da Silva EA, Medeiros WMB, Santos JPMD, et al. Evaluation of the efficacy and safety of cannabidiol-rich cannabis extract in children with autism spectrum disorder: randomized, double-blind and placebo-controlled clinical trial. Trends Psychiatr Psy 2022:ahead of print.
91. Thiele EA, Marsh ED, French JA, et al. GWPCARE4 Study Group. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2018;391:1085-96.
92. Metternich B, Wagner K, Geiger MJ, Hirsch M, Schulze-Bonhage A, Klotz KA. Cognitive and behavioral effects of cannabidiol in patients with treatment-resistant epilepsy. Epilepsy Behav 2021;114:107558.
93. Berry-kravis E, Hagerman R, Budimirovic D, et al. A pivotal study of ZYN002 cannabidiol (CBD) transdermal gel in children and adolescents with fragile X syndrome [CONNECT-FX (ZYN2-CL-016)]. Biol Psychiat 2021;89:S226-7.
94. Johnson D, Hagerman R. Chapter 33-Medical use of cannabidiol in fragile X syndrome. Medicinal usage of cannabis and cannabinoids. Elsevier; 2023. pp. 415-26.
95. Berry-Kravis EM, Harnett MD, Reines SA, et al. Inhibition of phosphodiesterase-4D in adults with fragile X syndrome: a randomized, placebo-controlled, phase 2 clinical trial. Nat Med 2021;27:862-70.
96. Hessl D, Sansone SM, Berry-Kravis E, et al. The NIH toolbox cognitive battery for intellectual disabilities: three preliminary studies and future directions. J Neurodev Disord 2016;8:35.
97. Lee HG, Imaichi S, Kraeutler E, et al. Site-specific R-loops induce CGG repeat contraction and fragile X gene reactivation. Cell 2023;186:2593-609.e18.