The Indian Journal of Pediatrics

, Volume 65, Issue 2, pp 181–191 | Cite as

Fragile X syndrome

  • John P. Phillips
  • Gregory A. Wilson
Symposium: Neurology—II


Fragile X syndrome is the most common form of inherited mental retardation. It is seen in people of all nationalities and in all areas of the world. Fragile X syndrome can be a devastating condition, as many boys are severely retarded and require multiple services. Treatment involves behaviour management techniques, appropriate school placement, community support for the family, and careful medical follow-up often including psychopharmacology. The genetics of fragile X syndrome is now understood, prenatal testing is available, and the disorder is preventable through appropriate genetic counselling. This review focuses on the neurobiology of fragile X syndrome, its clinical features and treatment.

Key words

Fragile X syndrome Mental retardation Trinucleotide repeat Martin-Bell syndrome 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Webb TP, Bundey SE, Thake AI, Todd J. Population incidence and segregation rations in the Martin-Bell syndrome.Am J Med Genet 1986; 23: 573–580.PubMedCrossRefGoogle Scholar
  2. 2.
    AAP Committee on Genetics. Health supervision for children with fragile X syndrome.Pediatrics 1996; 98: 297–300.Google Scholar
  3. 3.
    Rousseau F, Rouillard P, More ML, Khandjian EW, Morgan K. Prevalence of carriers or premutation-size alleles of the EMRI gene-and implications for the population genetics of the fragile X syndrome.Am J Hum Genet 1995; 57: 1006–1018.PubMedGoogle Scholar
  4. 4.
    Martin JP, Bell JJ Neurol Psych 1943; 6: 154–157.CrossRefGoogle Scholar
  5. 5.
    Hagerman RJ, Lugenbeel K, McLean SD, Taylor A. Learning-disabled males with a fragile X CGG expansion in the upper premutation size range.Pediatrics 1995; 97: 122–125.Google Scholar
  6. 6.
    Nelson DL. The fragile X syndromesSemin Cell Biol 1995; 6: 5–11.PubMedCrossRefGoogle Scholar
  7. 7.
    Lannery AV, Hirst MC, Knight SJ, et al. The fragile X syndrome.Biochem Biophys Acta 1995; 1271: 293–303.Google Scholar
  8. 8.
    Oostra BA, Halley DJ. Complex behaviour of simple repeats: the fragile X syndrome.Pediatr Res 1995; 38: 629–637.PubMedCrossRefGoogle Scholar
  9. 9.
    Siomi MC, Zhang Y, Siomi H,et al. Specific sequences in the fragile X syndrome protein FMR 1 and FXR proteins mediate their binding to 60S ribosomal subunits and the ineractions among them.Mol Cell Biol 1996; 16 (7): 3825–3832.PubMedGoogle Scholar
  10. 10.
    Oostra BA, Willems PJ. A fragile geneBioessays 1995; 17: 941–947.PubMedCrossRefGoogle Scholar
  11. 11.
    Rudelli RD, Brwon WT, Wisniewski Ket al. Adult fragile X syndrome. Cliniconeuropathologic findings.Acta Neuropathol 1985; 67: 289–295.PubMedCrossRefGoogle Scholar
  12. 12.
    Hinton VJ, Brown Wisniewski K, Rudell RD. Analysis of neocortex in three males with fragile X syndrome.Am J Med Genet 1991; 41: 289–294.PubMedCrossRefGoogle Scholar
  13. 13.
    Reiss AL, Lee J, Freund L. Neuroanatomy of fragile X syndrome: the temporal lobe.Neurology 1994; 44: 1317–1324.PubMedGoogle Scholar
  14. 14.
    Reiss AL, Freund LS, Baumgardner TL, et al. Contribution of the FMR-1 gene mutation to human intellectual dysfunction.Nat Genet 1995b; 11: 331–334.PubMedCrossRefGoogle Scholar
  15. 15.
    Courchesne E, Townsend J, Saitoh O. The brain in infantile autism: posterior fossa structures are abnormal.Neurology 1994; 44: 214–223.PubMedGoogle Scholar
  16. 16.
    Butler MG, Mangrum T, Gupta R, Singh DN. A 15-item checklist for screening mentally retarded males for the fragile X syndrome.Clin Genet 1991; 39: 347–354.PubMedCrossRefGoogle Scholar
  17. 17.
    Merlin G, Butler C, Allen Andrew,et al. Anthropometric comparison of mentally retarded males with and without the fragile X syndrome.Am J Med Genet 1991; 38: 260–268.CrossRefGoogle Scholar
  18. 18.
    Laing S, Partington M, Robinson H, Turner G. Clinical screening score for the fragile X (Martin-Bell) syndrome.Am J Med Genet 1991; 38: 256–259.PubMedCrossRefGoogle Scholar
  19. 19.
    Giangreco CA, Steele MW, Aston C,et al. A simplified six-item checklist for screening fragile X syndrome in the pediatric population.J Pediatr 1996; 129: 611–614.PubMedCrossRefGoogle Scholar
  20. 20.
    Maes B, Fryns JP, Van Walleghem M, Van den Berghe. Cognitive functioning and infomation processing of adult mentally retarded men with fragile X syndrome. Am J Med Genet 1994; 50: 190–200.PubMedCrossRefGoogle Scholar
  21. 21.
    Hay DA. Does IQ decline with age in fragile-X? A Methodological Critique.Am J Med Genet 1994; 51: 358–363.PubMedCrossRefGoogle Scholar
  22. 22.
    Reiss AL, Freund L. Fragile X Syndrome.Biol Psychiatry 1990; 27: 223–240.PubMedCrossRefGoogle Scholar
  23. 23.
    Freund L. Diagnosis and developmental issues for young children with fragile X syndrome.Infants and Young Children 1994; 6 (3): 34–45.CrossRefGoogle Scholar
  24. 24.
    Maes B, Fryns JP, Van Walleghen M, Van Den Berghe H. Fragile X syndrome and autism: a prevalent association or a misinterpreted connection.Genet. Couns 1993; 4: 245–263.PubMedGoogle Scholar
  25. 25.
    Hull C, Hagerman RJ. A study of the physical, behavioural and medical phenotype, including anthropometric measures, of females with fragile X syndrome.AJDC 1993; 147: 1236–1241.PubMedGoogle Scholar
  26. 26.
    Taylor AK, Safanda JF, Fall MZet al. Molecular predictors of cognitive involvement in female carriers of fragile X syndrome.JAMA 1994; 271: 507–514.PubMedCrossRefGoogle Scholar
  27. 27.
    deVries BB, Wiegers AM, Smits APet al. Mental status of females with an FMRI gene full mutation.Am J Hum Genet 1996; 58: 1025–32.Google Scholar
  28. 28.
    Dorn MB, Mazzoco MM, Hagerman RJ. Behavioral and psychiatric disorders in adult male carriers of fragile X.J Am Acad Child Adolesc Psychiatry 1994; 33 (2): 256–264.PubMedCrossRefGoogle Scholar
  29. 29.
    Dykens EM, Hodapp RM, Leckman JF. Behaviour and Development in fragile X syndrome.Dev Clinical Psychol and Psych 28.Google Scholar
  30. 30.
    Stackhause TM. Sensory integration concepts and fragile X syndrome. Teaching materials from the national fragile X association. Denver, CO, USA.Google Scholar
  31. 31.
    Barkley RA, DuPaul GJ, McMurry MB. Attention deficit disorder with and without hyperactivity: clinical response to three dose levels of methylphenidate.Pediatrics 1991; 87: 519–531.PubMedGoogle Scholar
  32. 32.
    Hagerman RJ, Murphy M, Wittenberger M. A controlled trial of stimulant medication in children with fragile X syndromeAm J Med Genet 1988; 30: 377–392.PubMedCrossRefGoogle Scholar
  33. 33.
    Berkovitch M, Pope E, Phillips J, Koren G. Pemoline-associated fulminant liver failure: testing the evidence for causation.Clin Pharmacol Ther 1995; 57: 696–698.PubMedCrossRefGoogle Scholar
  34. 34.
    Singer HS, Brown SS, Quaskey LAet al. The treatment of attention deficit hyper-activity disorder in Tourette's syndrome a double-blind placebo-controlled study with clonidine and desipramine.Pediatrics 1995; 95: 74–82.PubMedGoogle Scholar
  35. 35.
    Hilton DK, Martin CA, Heffron WMet al. Imipramine treatment of ADHD in a fragile X child.J Am Acad Child Adolesc Psychiatry 1991; 30: 831–834.PubMedCrossRefGoogle Scholar
  36. 36.
    Hagerman RJ, Riddle JE, Roberts LSet al. A survey of the efficacy of clonidine in fragile X syndrome.Dev Brain Dysf 1995; 8: 336–344.Google Scholar
  37. 37.
    Hagerman RJ, Fulton MJ, Leaman A,et al. A survey of fluoxetine therapy in fragile X syndrome.Dev Brain Dysf 1994; 7: 155–164.Google Scholar
  38. 38.
    Strom CM, Brusca RM, Pizzi WJ. Doubleblind, placebo-controlled crossover study of folic acid for the treatment of fragile X syndrome.Am J Med Genet 1992; 44: 676–682.PubMedCrossRefGoogle Scholar
  39. 39.
    Green WH.Child and Adolescent Clinical Psychopharmacology, 2nd ed. 1995. Williams and Williams, Baltimore.Google Scholar
  40. 40.
    Spencer T, Wilens T, Biederman J. Psychotropic medication for children and adolesents.Child and Adolescent Psychiatric Clinics of North America 1995; 4: 97–121.Google Scholar
  41. 41.
    Hagerman RJ, Wilson P, Staley LWet al. Evaluation of school children at high risk for fragile X syndrome utilizing buccal cell FMR-1 testing.Am J Med Genet 1994; 51: 474–481.PubMedCrossRefGoogle Scholar
  42. 42.
    Willemsen R, Mohkamising S, De Vries B,et al. Rapid antibody test for fragile X syndrome.Lancet 1995; 345: 1147–1148.PubMedCrossRefGoogle Scholar
  43. 43.
    Hagerman RJ, Cronister A.Fragile X Syndrome: Diagnosis, Treatment, and Research Baltimore Johns Hopkins University Press, 1996.Google Scholar
  44. 44.
    Maria BL, Medina CD, Karin BNet al. Gene therapy for neurological disease: benchtop discoveries to bedside applications. 1. The Bench.J Child Neurol 1997; 12: 1–12.PubMedGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 1998

Authors and Affiliations

  • John P. Phillips
    • 1
  • Gregory A. Wilson
    • 2
  1. 1.Department of Neurology, Section of Child NeurologyIndiana University Medical CentreIndianapolisUSA
  2. 2.Department of Pediatrics Section of Developmental PediatricsIndiana University Medical CentreIndianapolisUSA

Personalised recommendations