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Fragile X syndrome: Management in children and adolescents

Author
Hilde Van Esch, MD, PhD
Section Editors
Helen V Firth, DM, FRCP, DCH
Carolyn Bridgemohan, MD
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

The management of children and adolescents with fragile X syndrome (FXS, also called fragile X mental retardation syndrome, X-linked mental retardation and macro-orchidism, and Martin-Bell syndrome) is individualized according to the child's cognitive and behavioral symptoms, strengths, and weaknesses [1,2]. (See 'Evaluation to determine extent of disease' below.)

Interventions may include individualized education plans, speech and language therapy, occupational therapy, behavior therapy, and pharmacotherapy. Few controlled trials have been performed to assess the effectiveness of these interventions in children with FXS [3,4]. However, they are effective in children with other cognitive or behavioral problems. (See "Intellectual disability in children: Management, outcomes, and prevention" and "Specific learning disabilities in children: Educational management".)

The management of children and adolescents with FXS is discussed in this topic review. The clinical features, diagnosis, and prenatal screening are discussed separately. (See "Fragile X syndrome: Clinical features and diagnosis in children and adolescents" and "Prenatal screening and diagnosis for fragile X syndrome".)

GENETIC COUNSELING

Families of individuals with FXS should be referred to a geneticist or genetic counselor for a detailed discussion of the inheritance of the fragile X mental retardation 1 (FMR1) mutation and testing of other family members. FXS test results should be interpreted for the family according to the guidelines established by the National Society of Genetic Counselors and the American Society of Human Genetics [2,5]. Family members at risk for premutation or full mutation of FMR1 should receive information about possible emotional, neurologic, and reproductive problems (eg, premature ovarian insufficiency).

EVALUATION TO DETERMINE EXTENT OF DISEASE

Following initial diagnosis of FXS, children and adolescents should undergo a multidisciplinary evaluation to determine the extent of disease [1]. The evaluation should include:

                

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References
Top
  1. Saul RA, Tarleton JC. FMR1-related disorders. GeneReviews. www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=fragilex (Accessed on December 31, 2009).
  2. Hersh JH, Saul RA, Committee on Genetics. Health supervision for children with fragile X syndrome. Pediatrics 2011; 127:994.
  3. Garber KB, Visootsak J, Warren ST. Fragile X syndrome. Eur J Hum Genet 2008; 16:666.
  4. Berry-Kravis E, Potanos K. Psychopharmacology in fragile X syndrome--present and future. Ment Retard Dev Disabil Res Rev 2004; 10:42.
  5. Finucane B, Abrams L, Cronister A, et al. Genetic counseling and testing for FMR1 gene mutations: practice guidelines of the national society of genetic counselors. J Genet Couns 2012; 21:752.
  6. Health supervision for children with fragile X syndrome. American Academy of Pediatrics Committee on Genetics. Pediatrics 1996; 98:297.
  7. Visootsak J, Warren ST, Anido A, Graham JM Jr. Fragile X syndrome: an update and review for the primary pediatrician. Clin Pediatr (Phila) 2005; 44:371.
  8. Roberts JE, Mirrett P, Burchinal M. Receptive and expressive communication development of young males with fragile X syndrome. Am J Ment Retard 2001; 106:216.
  9. Weiskop S, Richdale A, Matthews J. Behavioural treatment to reduce sleep problems in children with autism or fragile X syndrome. Dev Med Child Neurol 2005; 47:94.
  10. Hills-Epstein J, Riley K, Sobesky W. The treatment of emotional and behavioral problems. In: Fragile X syndrome: Diagnosis, treatment, and research, 3rd ed, Hagerman RJ, Hagerman PJ (Eds), Johns Hopkins University Press, Baltimore 2002. p.339.
  11. Hagerman RJ, Berry-Kravis E, Kaufmann WE, et al. Advances in the treatment of fragile X syndrome. Pediatrics 2009; 123:378.
  12. Reiss AL, Hall SS. Fragile X syndrome: assessment and treatment implications. Child Adolesc Psychiatr Clin N Am 2007; 16:663.
  13. Durand VM, Carr EG. Social influences on "self-stimulatory" behavior: analysis and treatment application. J Appl Behav Anal 1987; 20:119.
  14. Iwata BA, Pace GM, Dorsey MF, et al. The functions of self-injurious behavior: an experimental-epidemiological analysis. J Appl Behav Anal 1994; 27:215.
  15. Hanley GP, Iwata BA, McCord BE. Functional analysis of problem behavior: a review. J Appl Behav Anal 2003; 36:147.
  16. Restivo L, Ferrari F, Passino E, et al. Enriched environment promotes behavioral and morphological recovery in a mouse model for the fragile X syndrome. Proc Natl Acad Sci U S A 2005; 102:11557.
  17. Braden ML. Education. In: Children with fragile X syndrome: A parent's guide, Woodbine House, Bethesda 2000. p.243.
  18. Wilson GN, Cooley WC. The fragile X syndrome. In: Preventive management of children with congenital anomalies and syndromes, Cambridge University Press, Cambridge, United Kingdom 2000. p.175.
  19. Hagerman R. Fragile X syndrome. In: The Zuckerman Parker Handbook of Developmental and Behavioral Pediatrics for Primary Care, 3rd ed, Augustyn M, Zuckerman B, Caronna EB (Eds), Lippincott Williams & Wilkins, Philadelphia 2011. p.218.
  20. Davids JR, Hagerman RJ, Eilert RE. Orthopaedic aspects of fragile-X syndrome. J Bone Joint Surg Am 1990; 72:889.
  21. Hagerman RJ, Altshul-Stark D, McBogg P. Recurrent otitis media in the fragile X syndrome. Am J Dis Child 1987; 141:184.
  22. Hagerman PJ, Stafstrom CE. Origins of epilepsy in fragile X syndrome. Epilepsy Curr 2009; 9:108.
  23. Berry-Kravis E. Epilepsy in fragile X syndrome. Dev Med Child Neurol 2002; 44:724.
  24. Musumeci SA, Hagerman RJ, Ferri R, et al. Epilepsy and EEG findings in males with fragile X syndrome. Epilepsia 1999; 40:1092.
  25. McConkie-Rosell A, Finucane B, Cronister A, et al. Genetic counseling for fragile x syndrome: updated recommendations of the national society of genetic counselors. J Genet Couns 2005; 14:249.
  26. Hagerman RJ, Murphy MA, Wittenberger MD. A controlled trial of stimulant medication in children with the fragile X syndrome. Am J Med Genet 1988; 30:377.
  27. Erickson CA, Stigler KA, Posey DJ, MCDougle CJ. Managing maladaptive behaviors in fragile X patients. J Fam Practice (on-line) 2006 www.jfponline.com/Pages.asp?AID=4443 (Accessed on December 22, 2009).
  28. Hagerman RJ, Riddle JE, Roberts LS, et al. Survey of the efficacy of clonidine in fragile X syndrome. Dev Brain Dysfunct 1995; 8:336.
  29. Hagerman RJ, Fulton MJ, Leaman A, et al. A survey of fluoxetine therapy in fragile X syndrome. Dev Brain Dysfunct 1994; 7:155.
  30. McCracken JT, McGough J, Shah B, et al. Risperidone in children with autism and serious behavioral problems. N Engl J Med 2002; 347:314.
  31. Shea S, Turgay A, Carroll A, et al. Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders. Pediatrics 2004; 114:e634.
  32. Nagaraj R, Singhi P, Malhi P. Risperidone in children with autism: randomized, placebo-controlled, double-blind study. J Child Neurol 2006; 21:450.
  33. Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA 2009; 302:1765.
  34. Gross C, Hoffmann A, Bassell GJ, Berry-Kravis EM. Therapeutic Strategies in Fragile X Syndrome: From Bench to Bedside and Back. Neurotherapeutics 2015; 12:584.
  35. Bear MF, Huber KM, Warren ST. The mGluR theory of fragile X mental retardation. Trends Neurosci 2004; 27:370.
  36. Spooren WP, Vassout A, Neijt HC, et al. Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine in rodents. J Pharmacol Exp Ther 2000; 295:1267.
  37. Tatarczyńska E, Klodzińska A, Chojnacka-Wójcik E, et al. Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. Br J Pharmacol 2001; 132:1423.
  38. Michalon A, Sidorov M, Ballard TM, et al. Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. Neuron 2012; 74:49.
  39. 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.
  40. Berry-Kravis E, Sumis A, Hervey C, et al. Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. J Dev Behav Pediatr 2008; 29:293.
  41. 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.
  42. Utari A, Chonchaiya W, Rivera SM, et al. Side effects of minocycline treatment in patients with fragile X syndrome and exploration of outcome measures. Am J Intellect Dev Disabil 2010; 115:433.
  43. Paribello C, Tao L, Folino A, et al. Open-label add-on treatment trial of minocycline in fragile X syndrome. BMC Neurol 2010; 10:91.
  44. 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.
  45. Chao HT, Chen H, Samaco RC, et al. Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature 2010; 468:263.
  46. 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.
  47. Erickson CA, Mullett JE, McDougle CJ. Brief report: acamprosate in fragile X syndrome. J Autism Dev Disord 2010; 40:1412.
  48. Lemonnier E, Robin G, Degrez C, et al. Treating Fragile X syndrome with the diuretic bumetanide: a case report. Acta Paediatr 2013; 102:e288.
  49. Pomponi MG, Neri G. Butyrate and acetyl-carnitine inhibit the cytogenetic expression of the fragile X in vitro. Am J Med Genet 1994; 51:447.
  50. Rueda JR, Guillén V, Ballesteros J, et al. L-acetylcarnitine for treating fragile X syndrome. Cochrane Database Syst Rev 2015; :CD010012.
  51. Berry-Kravis E, Krause SE, Block SS, et al. Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial. J Child Adolesc Psychopharmacol 2006; 16:525.
  52. Busquets-Garcia A, Gomis-González M, Guegan T, et al. Targeting the endocannabinoid system in the treatment of fragile X syndrome. Nat Med 2013; 19:603.
  53. Sharma A, Hoeffer CA, Takayasu Y, et al. Dysregulation of mTOR signaling in fragile X syndrome. J Neurosci 2010; 30:694.
  54. Irwin SA, Patel B, Idupulapati M, et al. Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet 2001; 98:161.
  55. Hayashi ML, Rao BS, Seo JS, et al. Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice. Proc Natl Acad Sci U S A 2007; 104:11489.
  56. Dolan BM, Duron SG, Campbell DA, et al. Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486. Proc Natl Acad Sci U S A 2013; 110:5671.
  57. Merenstein SA, Sobesky WE, Taylor AK, et al. Molecular-clinical correlations in males with an expanded FMR1 mutation. Am J Med Genet 1996; 64:388.