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Journal of Neurology

Erschienen in:

01.03.2012 | Review

Fragile X-associated disorders: a clinical overview

verfasst von: Anne Gallagher, Brian Hallahan

Erschienen in: Journal of Neurology | Ausgabe 3/2012

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Abstract

Fragile X Syndrome (FraX) is the most common inherited cause of learning disability worldwide. FraX is an X-linked neuro-developmental disorder involving an unstable trinucleotide repeat expansion of cytosine guanine guanine (CGG). Individuals with the full mutation of FraX have >200 CGG repeats with premutation carriers having 55–200 CGG repeats. A wide spectrum of physical, behavioural, cognitive, psychiatric and medical problems have been associated with both full mutation and premutation carriers of FraX. In this review, we detail the clinical profile and examine the aetiology, epidemiology, neuropathology, neuroimaging findings and possible management strategies for individuals with both the full mutation and premutation of FraX.

Fernandez-Carvajal I, Walichiewicz P, Xiaosen X et al (2009) Screening for expanded alleles of the FMR1 gene in blood spots from newborn males in a Spanish population. J Mol Diagn 11:324–328PubMed

Crawford DC, Meadows KL, Newman JL et al (2002) Prevalence of the fragile X syndrome in African Americans. Am J Med Genet 110:226–233PubMed

Pesso R, Berkenstadt M, Cuckle H et al (2000) Screening for fragile X syndrome in women of reproductive age. Prenat Diagn 20:611–614PubMed

Hagerman R, Hagerman P (2002) The fragile X premutation: into the phenotypic fold. Curr Opin Genet Dev 12:278–283PubMed

Toledano-Alhadef H, Basel-Vanagaite L, Magal N et al (2001) Fragile-X carrier screening and the prevalence of premutation and full-mutation carriers in Israel. Am J Hum Genet 69:351–360PubMed

Rousseau F, Rouillard P, Morel ML, Khandjian EW, Morgan K (1995) Prevalence of carriers of premutation-size alleles of the FMR1 gene—and implications for the population genetics of the fragile X syndrome. Am J Hum Genet 57:1006–1018PubMed

Dombrowski C, Lévesque S, Morel ML, Rouillard P, Morgan K, Rousseau F (2002) Premutation and intermediate-size FMR1 alleles in 10572 males from the general population: loss of an AGG interruption is a late event in the generation of fragile X syndrome alleles. Hum Mol Genet 11:371–378PubMed

Tzeng C, Tsai L, Hwu W et al (2005) Prevalence of the FMR1 mutation in Taiwan assessed by large-scale screening of newborn boys and analysis of DXS548 FRAXAC1 haplotype. Am J Med Genet A 133:37–43

Grigsby JP, Kemper MB, Hagerman RJ, Myers CS (1990) Neuropsychological dysfunction among affected heterozygous fragile X females. Am J Med Genet 35:28–35PubMed

10.

Grigsby J, Kemper MB, Hagerman RJ (1992) Verbal learning and memory among heterozygous fragile X females. Am J Med Genet 43:111–115PubMed

11.

Mazzocco MM, Pennington BF, Hagerman RJ (1993) The neurocognitive phenotype of female carriers of fragile X: additional evidence for specificity. J Dev Behav Pediatr 14:328–335PubMed

12.

Verkerk AJMH, Pieretti M, Sutcliffe JS et al (1991) Identification of a gene (FMR1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65:905–914

13.

Yu S, Pritchard M, Kremer E et al (1991) Fragile-X genotype characterized by an unstable region of DNA. Science 252:1179–1181

14.

Van der Molen M, Huizinga M, Huizenga HM et al (2010) Profiling fragile X syndrome in males: strengths and weaknesses in cognitive abilities. Res Dev Disabil 31:426–439PubMed

15.

Mandel JL, Biancalana V (2004) Fragile X mental retardation syndrome: from pathogenesis to diagnostic issues. Growth Horm IGF Res 14(Suppl A):S158–S165PubMed

16.

Hagerman R, Hagerman P (eds) (2002) Fragile X syndrome: diagnosis, treatment and research, 3rd edn. John Hopkins University Press, Baltimore, pp 3–109

17.

Meryash DL, Cronk CE, Sachs B, Gerald PS (1984) An anthropometric study of males with the fragile-X syndrome. Am J Med Genet 17:159–174PubMed

18.

Hagerman RJ (2002) Physical and behavioural phenotype. In: Hagerman RJ, Hagerman P (eds) Fragile X syndrome: diagnosis, treatment and research, 3rd edn. The Johns Hopkins University Press, Baltimore, pp 3–109

19.

Chonchaiya W, Schneider A, Hagerman RJ (2009) Fragile X: a family of disorders. Adv Pediatr 56:165–186PubMed

20.

Berry-Kravis E (2002) Epilepsy in fragile X syndrome. Dev Med Child Neurol 42:724–728

21.

Jacquemont S, Hagerman RJ, Hagerman P, Leehey M (2007) Fragile-X syndrome and fragile X-associated tremor/ataxia syndrome: two faces of FMR1. Lancet Neurol 6:45–55PubMed

22.

Reiss AL, Freund LS (1990) Fragile X syndrome, DSM-III-R, and autism. J Am Acad Child Adolesc Psychiatry 29:885–891PubMed

23.

Scharfenaker S, O’Connor R, Stackhouse R et al (1996) An integrated approach to intervention. In: Hagerman R, Cronister A (eds) Fragile X syndrome: diagnosis treatment and research. The Johns Hopkins University Press, Baltimore, pp 349–411

24.

Levitas A (1996) Neuropsychiatric aspects of fragile X syndrome. Semin Clin Neuropsychiatry 1:154–167PubMed

25.

Lachiewicz AM, Spiridigliozzi GA, Gullion CM et al (1994) Aberrant behaviours of young boys with fragile X syndrome. Am J Ment Retard 98:567–579PubMed

26.

Hatton D, Sideris J, Skinner M et al (2006) Autistic behaviour in children with fragile X syndrome: prevalence, stability, and the impact of FMRP. Am J Med Genet 140:1804–1813

27.

Kaufmann WE, Cortell R, Kau AS et al (2004) Autism spectrum disorder in fragile X syndrome: communication, social interaction, and specific behaviors. Am J Med Genet 129A:225–234PubMed

28.

Rogers SJ, Wehner EA, Hagerman RJ et al (2001) The behavioural phenotype in fragile X: symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders. J Dev Behav Pediatr 22:409–417PubMed

29.

Harris S, Hessl D, Goodlin-Jones B et al (2008) Autism profiles of males with fragile x syndrome. Am J Ment Retard 113:427–438

30.

Demark JL, Feldman MA, Holden JJ (2003) Behavioural relationship between autism and fragile X syndrome. Am J Ment Retard 108:314–326PubMed

31.

Bailey DB, Mesibov GB, Hatton DD et al (1998) Autistic behaviour in young boys with fragile X syndrome. J Autism Dev Disord 28:6

32.

Hessl D, Tassone F, Cordeiro L et al (2008) Brief report: aggression and stereotypic behaviour in males with fragile X syndrome—moderating secondary genes in a “single gene” disorder. J Autism Dev Disord 38:184–189PubMed

33.

Tsiouris JA, Brown WT (2004) Neuropsychiatric symptoms of fragile X syndrome: pathophysiology and pharmacotherapy. CNS Drugs 18:687–703PubMed

34.

Hagerman RJ, Hills J, Scharfnaker S et al (1999) Fragile X syndrome and selective mutism. Am J Med Genet 83:313–317PubMed

35.

Cordeiro L, Ballinger E, Hagerman R, Hessl D (2011) Clinical assessment of DSM-IV anxiety disorders in fragile X syndrome: prevalence and characterization. J Neurodev Disord 3:1–11

36.

Hagerman R, Kemper M, Hudson M (1985) Learning disabilities and attentional problems in boys with the fragile X syndrome. Am J Dis Child 139:674–678PubMed

37.

Hessl D, Nguyen DV, Green C et al (2008) A solution to limitations of cognitive testing in children with intellectual disabilities: the case of fragile X syndrome. J Neurodev Disord 1:33–45

38.

Dykens EM, Hoddap RM, Leckman JF (1987) Strengths and weaknesses in the intellectual functioning of males with fragile X syndrome. Am J Med Genet 28:13–15

39.

Freund LS, Reiss AL (1991) Cognitive profiles associated with the fragile X syndrome in males and females. Am J Med Genet 38:542–547PubMed

40.

Kemper MB, Hagerman RJ, Ahmad RS, Mariner R (1986) Cognitive profiles and the spectrum of clinical manifestations in heterozygous fragile X females. Am J Med Genet 23:139–156PubMed

41.

Cornish KM, Munira F, Cross G (1999) Spatial cognition in males with fragile X syndrome: evidence for a neuropsychological phenotype. Cortex 35:263–271

42.

Shapiro MB, Murphy DGM, Hagerman RJ et al (1995) Adult fragile X syndrome: neuropsychology, brain anatomy and metabolism. Am J Med Genet 60:480–493

43.

Munir F, Cornish K, Wilding J (2000) A neuropsychological profile of attention deficits in young males with fragile X syndrome. Neuropsychologia 38:1261–1270PubMed

44.

Kaufman PM, Leckman JF, Ort SI (1990) Delayed response performance in males with fragile X syndrome. J Clin Exp Neuropsychol 12:69

45.

Munir F, Cornish KM, Wilding J (2000) Nature of the working memory deficit in fragile X syndrome. Brain Cogn 44:387–401

46.

Escalante JA, Grunspun H, Frota-Pessoa O (1971) Severe sex-linked mental retardation. J Genet Hum 19:137–140

47.

Loesch DZ, Hay DA (1988) Clinical features and reproductive patterns in fragile X female heterozygotes. J Med Genet 25:407–414PubMed

48.

Hagerman RJ, Jackson C, Amiri K et al (1992) Girls with fragile X syndrome: physical and neurocognitive status and outcome. Pediatrics 89:395–400PubMed

49.

Moore PS, Chudley AE, Winter JS (1990) True precocious puberty in a girl with the fragile X syndrome. Am J Med Genet 37:265–267PubMed

50.

Riddle JE, Cheema A, Sobesky WE et al (1998) Phenotypic involvement in females with the FMR1 gene mutation. Am J Ment Retard 102:590–601PubMed

51.

Tassone F, Hagerman RJ, Ikle DN et al (1999) FMR1 protein expression as a potential prognostic indicator in fragile X syndrome. Am J Med Genet 84:250–261PubMed

52.

Loesch DZ, Huggins RM, Hagerman RJ (2004) Phenotypic variation and FMR1 protein levels in fragile X. Med Retard Dev Disabil Res Rev 10:31–41

53.

Dyer-Friedman J, Glaser B, Hessl D et al (2002) Genetic and environmental influences on the cognitive outcomes of children with fragile X syndrome. J Am Acad Child Adolesc Psychiatry 41(3):237–244PubMed

54.

Reiss AL, Freund LS, Baumgardner TL, Abrams MT, Denckla MB (1995) Contribution of the FMR1 gene mutation to human intellectual dysfunction. Nat Genet 11:331–334PubMed

55.

Freund L, Reiss AL, Abrams M (1993) Psychiatric disorders associate with fragile X in the young female. Paediatrics 91:321–329

56.

Kaplan SC, Hong GK, Weinhold C (1986) Epidemiology of depressive symptomatology in adolescents. Am J Psychiatry 18:343–354

57.

Roberts JE, Bailey DB Jr, Mankowski J et al (2009) Mood and anxiety disorders in females with the FMR1 premutation. Am J Med Genet 150B:130–139PubMed

58.

Reiss AL, Hagerman RJ, Vingradov S, Abrams M, King RJ (1988) Psychiatric disability in female carriers of the fragile X chromosome. Arch Gen Psychiatry 45:25–30PubMed

59.

Freund LS, Reiss AL (1992) Chromosome fragility and psychopathology in obligate female carriers of the fragile X chromosome. Arch Gen Psychiatry 49:54–60PubMed

60.

Hagerman RJ, Staley LW, O’Connor R et al (1996) Learning disabled males with a fragile X CGG expansion in the upper premutation range. Paediatrics 97:122–126

61.

Loesch DZ, Hay DA, Mulley JC (1994) Transmitting males and carrier females in fragile X revisited. Am J Med Genet 51:392–399PubMed

62.

Moore CJ, Daly EM, Tassone F et al (2004) The effect of pre-mutation of X chromosome CGG trinucleotide repeats on brain anatomy. Brain 127:2672–2681PubMed

63.

Dorn MB, Mazzocco MM, Hagerman RJ (1994) Behavioural and psychiatric disorders in adult male carriers of fragile X. J Am Acad Child Adolesc Psychiatry 33:256–264PubMed

64.

Farzin F, Perry H, Hessl D et al (2006) Autism spectrum disorders and attention-deficit/hyperactivity disorder in boys with the fragile X premutation. J Dev Behav Pediatr 27(2):S137–S144PubMed

65.

Aziz M, Stathopulu E, Callias M et al (2003) Clinical features of boys with fragile X premutations and intermediate alleles. Am J Med Genet 121B(1):119–127PubMed

66.

Goodlin-Jones B, Tassone F, Gane LW, Hagerman RJ (2004) Autistic spectrum disorder and the fragile X premutation. J Dev Behav Pediatr 25(6):392–398PubMed

67.

Cornish KM, Kogan C, Turk J et al (2005) The emerging fragile X premutation phenotype: evidence from the domain of social cognition. Brain Cogn 57(1):53–60PubMed

68.

Bailey DB Jr, Hatton DD, Mesibov GB, Ament N, Skinner M (2000) Early development, temperament and functional impairment in autism and fragile X syndrome. J Autism Dev Disord 30:49–59PubMed

69.

Bourgeois JA, Coffey SM, Rivera SM et al (2009) A review of fragile X premutation disorders: expanding the psychiatric perspective. J Clin Psychiatry 70(6):852–862PubMed

70.

Hull C, Hagerman RJ (1993) A study of the physical, behavioural, and medical phenotype, including anthropometric measures of females with fragile X syndrome. Am J Dis Child 147:1236–1241PubMed

71.

Bennetto L, Pennington BF (2002) Neuropsychology. In: Hagerman RJ, Hagerman PJ (eds) Fragile X syndrome: diagnosis, treatment and research, 3rd edn. The Johns Hopkins University Press, Baltimore

72.

Franke P, Leboyer M, Gansicke M et al (1998) Genotype-phenotype relationship in female carriers of the premutation and full mutation of FMR-1. Psychiatry Res 80:113–127PubMed

73.

Rodriguez-Revenga L, Madrigal I, Pagonabarraga J et al (2009) Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families. Eur J Hum Genet 17:1359–1362PubMed

74.

Constant EL, Adam S, Seron X et al (2005) Anxiety and depression, attention, and executive functions in hypothyroidism. J Int Neuropsychol Soc 11:535–544PubMed

75.

Larisch R, Kley K, Nikolaus S et al (2004) Depression and anxiety in different thyroid function states. Horm Metab Res 36:650–653PubMed

76.

Hundscheid RD, Braat DD, Kiemeney LA et al (2001) Increased serum FSH in female fragile X premutation carriers with either regular menstrual cycles or on oral contraceptives. Human Reprod 16:457–462

77.

Allingham-Hawkins DJ, Brown CA, Babul R et al (1999) Fragile X premutation is a significant risk factor for premature ovarian failure. The international collaborative POF in fragile X study—preliminary data. Am J Med Genet 83:322–325PubMed

78.

Hagerman RJ, Leehey M, Heinrichs W et al (2001) Intention tremor, Parkinsonism and generalized brain atrophy in older male carriers of fragile X. Neurology 57:127–130PubMed

79.

Jacquemont S, Hagerman RJ, Leehey M et al (2003) Fragile X premutation tremor/ataxia syndrome: molecular, clinical, and neuroimaging correlates. Am J Hum Genet 72:869–878PubMed

80.

Leehey MA, Munhoz RP, Lang AE et al (2003) The fragile X premutation presenting as essential tremor. AMA Arch Neurol 60:117–121PubMed

81.

Coffey SM, Cook K, Tartaglia N et al (2008) Expanded clinical phenotype of women with the FMR1 premutation. Am J Med Genet 146A:1009–1016PubMed

82.

Cornish KM, Kogan CS, Li L et al (2009) Lifespan changes in working memory in fragile X premutation males. Brain Cogn 69:551–558PubMed

83.

Hunter JE, Allen EG, Ann Abramowitz A et al (2008) No evidence for a difference in neuropsychological profile among carriers and non-carriers of the FMR1 premutation in adults under the age of 50. Am J Hum Genet 83:692–702PubMed

84.

Conway GS, Hettitarachein S, Murray A, Jacobs PA (1995) Fragile X premutations in familial premature ovarian failure. Lancet 346:309–310PubMed

85.

Sherman SL (2000) Premature ovarian failure in the fragile X syndrome. Am J Med Genet 97:189–194PubMed

86.

Tassone F, Hagerman RJ, Taylor AK, Gane LW, Godfrey TE, Hagerman PJ (2000) Elevated levels of FMR1 mRNA in carrier males: a new mechanism of involvement in the fragile-X syndrome. Am J Hum Genet 66:6–15PubMed

87.

Stevenson RE, Schwartz CE, Schroer RJ (2000) X-linked mental retardation. Oxford University Press, New York

88.

Lubs H (1969) A marker X chromosome. Am J Hum Genet 21:231–244PubMed

89.

Sutherland GR (1977) Fragile sites on human chromosomes: demonstration of their dependence on the type of tissue culture medium. Science 197:265–266PubMed

90.

Merenstein SA, Sobesky WE, Taylor AK et al (1996) Molecular clinical correlations in males with an expanded FMR1 mutation. Am J Med Genet 64:388–394PubMed

91.

Reddy KS (2005) Cytogenetic abnormalities and fragile-X syndrome in autism spectrum disorder. BMC Med Genet 18:3

92.

Nolin SL, Brown WT, Glicksman A et al (2003) Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles. Am J Hum Genet 72:454–464PubMed

93.

Zalfa F, Bagni C (2004) Molecular insights into mental retardation: multiple functions for the fragile X mental retardation protein? Curr Issues Mol Biol 6:73–88PubMed

94.

Abitbol M, Menini C, Delezoide AL et al (1993) Nucleus basalis magnocellularis and hippocampus are the major sites of FMR1 expression in the human fetal brain. Nat Genet 4:147–153PubMed

95.

Hinds HL, Ashley CT, Sutcliffe JS et al (1993) Tissue specific expression of FMR1 provides evidence for a functional role in fragile X syndrome. Nat Genet 3:36–43PubMed

96.

Zhang Y, O’Connor P, Siomi M et al (1995) The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2. EMBO J 14:5358–5366PubMed

97.

Eberhart DE, Malter HE, Feng Y, Warren ST (1996) The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals. Hum Mol Genet 5:1083–1091PubMed

98.

Adinolfi S, Bagni C, Musco G et al (1999) Dissecting FMR1, the protein responsible for fragile X syndrome, in its structural and functional domains. RNA 5:1248–1258PubMed

99.

Schaeffer C, Beaulande M, Ehresmann C et al (2003) The RNA binding protein FMRP: new connections and missing links. Biol Cell 95:221–228PubMed

100.

Ceman S, Brown V, Warren ST (1999) Isolation of an FMRP-associated messenger ribonucleoprotein particle and identification of nucleolin and the fragile X related proteins as components of the complex. Mol Cell Biol 19:7925–7932PubMed

101.

Carola JM, Mcllwain KL, Nieuwenhuien IM et al (2002) Knockout mouse model for FXR2: a model for mental retardation. Hum Mol Genet 11:487–498

102.

Broadie V, Pan L (2005) Translational complexity of the fragile X mental retardation protein: insights form the fly. Mol Cell 17:757–759PubMed

103.

Bilousova TV, Dansie L, Ngo M et al (2009) Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model. J Med Genet 46:94–102PubMed

104.

Antar LN, Li C, Zhang H, Carroll RC, Bassell GC (2006) Local functions for FMRP in axon growth cone motility and activity-dependent regulation of filopodia and spine synapses. Mol Cell Neurosci 32:37–48PubMed

105.

Gantois I, Vandesompele J, Speleman F et al (2006) Expression profiling reveals underexpression of the GABAA receptor subunit delta in the fragile X knockout mice model. Neurobiol Dis 21:346–357PubMed

106.

Mihalek RM, Banerjee PK, Korpi ER et al (1999) Attenuated sensitivity to neuroactive steroids in γ-aminobutyrate type A receptor delta subunit knockout mice. Proc Natl Acad Sci USA 96:12905–12910PubMed

107.

D’Hulst C, De Geest N, Reeve SP et al (2006) Decreased expression of the GABAA receptor in fragile X syndrome. Brain Res 1121:238–245PubMed

108.

D’Hulst C, De Geestb N, Reeveb S et al (2009) Decreased expression of the GABAA receptor in fragile X syndrome. Brain Res 1253:176–183PubMed

109.

Huber KM, Kayser MS, Bear MF (2000) Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent long-term depression. Science 288:1254–1257PubMed

110.

Huber KM, Roder JC, Bear MF (2001) Chemical induction of mGluR5- and protein synthesis-dependent long-term depression in hippocampal area CA1. J Neurophysiol 86:321–325PubMed

111.

Greenough WT, Klintsova AY, Irwin SA et al (2001) Synaptic regulation of protein synthesis and the fragile X protein. Proc Natl Acad Sci USA 98:7101–7106PubMed

112.

Weiler IJ, Irwin SA, Klintsova AY et al (1997) Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation. Proc Natl Acad Sci USA 94:5395–5400PubMed

113.

Grossman AW, Aldridge GM, Weiler IJ, Greenough WT (2006) Local protein synthesis and spine morphogenesis: fragile X syndrome and beyond. J Neurosci 26:7151–7155PubMed

114.

Aschrafi A, Cunningham BA, Edelman GM, Vanderklish PW (2005) The fragile X mental retardation protein and group I metabotropic glutamate receptors regulate levels of mRNA granules in brain. Proc Natl Acad Sci USA 102:2180–2185PubMed

115.

Bear MF, Dolen G, Osterweil E, Nagarajan N (2008) Fragile X: translation in action. Neuropsychopharmacology 33:84–87PubMed

116.

Bear MF, Huber KM, Warren ST (2004) The mGluR theory of fragile X mental retardation. Trends Neurosci 27:370–377PubMed

117.

Silverman JL, Tolu S, Barkan C, Crawley J (2010) Repetitive self-grooming behavior in the BTBR mouse model of autism is blocked by the mGluR5 antagonist MPEP. Neuropsychopharmacology 35:976–989PubMed

118.

Jacquemont S, Curie A, des Portes V et al (2011) Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci Transl Med 3(64):64ra1PubMed

119.

Friedmann C, Davis L, Ciccone P, Rubin R (1980) Phase II double-blind controlled study of a new anxiolytic, fenobam (McN-3377) vs placebo. Curr Ther Res 27:144–151

120.

Pecknold JC, McClure DJ, Appeltauer L, Wrzesinski L, Allan T (1982) Treatment of anxiety using fenobam (a nonbenzodiazepine) in a double-blind standard (diazepam) placebo-controlled study. J Clin Psychopharmacol 2:129–133PubMed

121.

Berry-Kravis E, Hessl D, Coffey S et al (2009) A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. J Med Genet 46:266–271PubMed

122.

Paribello C, Tao L, Folino A et al (2010) Open-label add-on treatment trial of minocycline in fragile X syndrome. BMC Neurol 10:91PubMed

123.

Utari A, Chonchaiya W, Rivera SM et al (2010) Side effects of minocycline treatment in patients with fragile X syndrome and exploration of outcome measures. Am J Intellect Dev Disabil 115:433–443PubMed

124.

Irwin SA, Idupulapati M, Gilbert ME et al (2002) Dendritic spine and dendritic field characteristics of layer V pyramidal neurons in the visual cortex of fragile-X knockout mice. Am J Med Genet 111:140–146PubMed

125.

Irwin SA, Patel B, Idupulapati M et al (2001) Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet 98:161–167PubMed

126.

Hinton VJ, Brown WT, Wisniewski K, Rudelli RD (1991) Analysis of neocortex in three males with fragile X syndrome. Am J Med Genet 41:289–294PubMed

127.

Irwin SA, Galvez R, Greenough WT (2000) Dendritic spine structural anomalies in fragile-X mental retardation syndrome. Cereb Cortex 10:1038–1044PubMed

128.

Koukoui SD, Chaudhuri A (2007) Neuroanatomical, molecular, genetic, and behavioural correlates of fragile X syndrome. Brain Res Rev 53:27–38PubMed

129.

Pfeiffer BE, Huber KM (2007) Fragile X mental retardation protein induces synapse loss through acute postsynaptic translational regulation. J Neurosci 27:3120–3130PubMed

130.

Pfeiffer BE, Zang T, Wilkerson JR et al (2010) Fragile X mental retardation protein is required for synapse elimination by the activity-dependent transcription factor MEF2. Neuron 66:191–197PubMed

131.

Greco CM, Berman RF, Martin RM et al (2006) Neuropathology of fragile X-associated tremor/ataxia syndrome (FXTAS). Brain 129:243–255PubMed

132.

Tassone F, Iwahahi C, Hagerman PJ (2004) FMR1 RNA within the intranuclear inclusions of Fragile X associated tremor/ataxia syndrome. RNA Biol 1:103–105PubMed

133.

Greco C, Hagerman RJ, Tassone F et al (2002) Neuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers. Brain 125:1760–1771PubMed

134.

Reiss AL, Abrams MT, Greenlaw R, Freund L, Denckla MB (1995) Neurodevelopmental effects of the FMR1 full mutation in humans. Nat Med 1:159–167PubMed

135.

Eliez S, Blasey CM, Freund LS et al (2001) Brain anatomy, gender and IQ in children and adolescents with fragile X syndrome. Brain 124:168–1610

136.

Gothelf D, Furfaro JA, Hoeft F et al (2008) Neuroanatomy of fragile X syndrome is associated with aberrant behaviour and the fragile X mental retardation protein (FMR1 PROTEIN). Ann Neurol 63:40–51PubMed

137.

Hoeft F, Lightbody AA, Hazlett HC et al (2008) Morpohometric spatial patterns differentiating boys with fragile X syndrome, typically developing boys, developmentally delayed boys aged 1 to 3 years. Arch Gen Psychiatry 65:1087–1097PubMed

138.

Hazlett HC, Poe MD, Lightbody AA et al (2009) Teasing apart the heterogeneity of autism: same behaviour, different brains in toddlers with fragile X syndrome and autism. J Neurodev Disord 1:181–190

139.

Hallahan B, Craig M, Toal F et al (2010) In vivo brain anatomy of adult males with fragile X syndrome: an MRI study. Neuroimage 54:16–24PubMed

140.

Wilson LB, Tregellas JR, Hagerman RJ et al (2009) A voxel-based morphometry comparison of regional gray matter between fragile X syndrome and autism. Psychiatry Res 174:138–145PubMed

141.

Mostofsky SH, Mazzocco MM, Aakalu G et al (1998) Decreased cerebellar posterior vermis size in fragile X syndrome: correlation with neurocognitive performance. Neurology 51:121–130

142.

Reiss AL, Aylward E, Freund LS et al (1991) Neuroanatomy of fragile X syndrome: the posterior fossa. Ann Neurol 29:26–32PubMed

143.

Reiss AL, Abrams MT, Greenlaw R et al (1995) Neurodevelopmental effects of the FMR-1 full mutation in humans. Nat Med 1:159–167PubMed

144.

Guerreiro MM, Camargo EE, Kato M et al (1998) Fragile X syndrome, Clinical, electroencephalographic and neuroimaging characteristics. Aq Neuropsiquiatr 56:18–23

145.

Reiss AL, Lee J, Freund L (1994) Neuroanatomy of fragile X syndrome: the temporal lobe. Neurology 44:1317–1324PubMed

146.

Kates WR, Abrams MT, Kaufmann WE, Breiter SN, Reiss AL (1997) Reliability and validity of MRI measurement of the amygdala and hippocampus in children with fragile X syndrome. Psychiatry Res 76:15–27PubMed

147.

Jäkälä P, Hänninen T, Ryynänen M et al (1997) Fragile-X: neuropsychological test performance, CGG triplet repeat lengths, and hippocampal volumes. J Clin Invest 100:331–338PubMed

148.

Cornish KM, Munira F, Cross G (2001) Differential impact of the FMR1 full mutation on memory and attention functioning: a neuropsychological perspective. J Cogn Neurosci 13:144–150PubMed

149.

Hoeft F, Hernandez A, Sudharshan P et al (2007) Fronto-striatal dysfunction and potential compensatory mechanisms in male adolescents with fragile X syndrome. Hum Brain Map 28:543–554

150.

Allen G, Buxton R, Wong EC, Courchesne E (1997) Attentional activation of the cerebellum independent of motor involvement. Science 275:1940–1943PubMed

151.

Townsend J, Courchesne E, Covington J et al (1999) Spatial attention deficits in patients with acquired or developmental cerebellar abnormality. J Neurosci 19:5632–5643PubMed

152.

Ronning C, Sundet K, Due-Tonnessen B et al (2005) Persistent cognitive dysfunction secondary to cerebellar injury in patients treated for posterior fossa tumors in childhood. Pediatr Neurosurg 41:15–21PubMed

153.

Brunberg JA, Jacquemont S, Hagerman RJ et al (2002) Fragile X permutation carriers: characteristic MR imaging findings in adult males with progressive cerebellar and cognitive dysfunction. Am J Neuroradiol 23:1757–1766PubMed

154.

Loesch DZ, Litewka L, Brotchie P et al (2005) Magnetic resonance imaging study in older fragile X premutation male carriers. Ann Neurol 58:326–330PubMed

155.

Cohen S, Masyn K, Adams J et al (2006) Molecular and imaging correlates of the fragile X-associated tremor/ataxia syndrome. Neurology 67:1426–1431PubMed

156.

Adams JS, Adams PE, Nguyen D et al (2007) Volumetric brain changes in females with fragile X-associated tremor/ataxia syndrome (FXTAS). Neurology 69:851–859PubMed

157.

Koldewyn K, Hessl D, Adams J et al (2008) Reduced hippocampal activation during recall is associated with elevated FMR1 mRNA and psychiatric symptoms in men with the fragile X premutation. Brain Imaging Behav 2:105–116PubMed

158.

Hessl D, Rivera S, Koldewyn K et al (2007) Amygdala dysfunction in men with the fragile X premutation. Brain 130:404–416PubMed

159.

Adams PE, Adams JS, Nguyen DV et al (2010) Psychological symptoms correlate with reduced hippocampal volume in fragile X premutation carriers. Am J Med Genet Part B 153B:775–785PubMed

160.

Oberle I, Rousseau F, Heitz D et al (1991) Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science 252:1097–1102

161.

Willemsen R, Oosterwijk JC, Los FJ et al (1996) Prenatal diagnosis of fragile X syndrome. Lancet 348:967–968PubMed

162.

Iwahashi C, Tassone F, Hagerman RJ et al (2009) A quantitative ELISA assay for the fragile X mental retardation 1 protein. J Mol Diagn 11:281–289PubMed

163.

McConkie-Rosell A, Finucane B, Cronister A, Abrams L, Bennett RL, Pettersen BJ (2005) Genetic counselling for fragile X syndrome: updated recommendations of the NSGC. J Genet Couns 14:249–270PubMed

164.

Fragile X (1994) syndrome: diagnostic and carrier testing (policy statement). Am J Med Genet 53:380–381

165.

Hall DA, Berry-Kravis E, Hagerman RJ et al (2006) Symptomatic treatment in the fragile X associated tremor/ataxia syndrome. Mov Disord 21:1741–1744PubMed

166.

Hagerman RJ, Murphy MA, Wittenberger MD (1988) A controlled trial of stimulant medication in children with fragile X syndrome. Am J Med Genet 30:377–392PubMed

167.

Torroi MG, Vernacotola S, Mariotti P et al (1999) Double-blind placebo controlled study of L-acetylcarnitine for the treatment of hyperactive behaviour in fragile x syndrome. Am J Med Genet 87:366–368

168.

Yan QJ, Rammal M, Tranfaglia M, Bauchwitz RP (2005) Suppression of two major fragile X syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 49:1053–1066PubMed

169.

McBride SM, Choi CH, Wang Y et al (2005) Pharmacological rescue of synaptic plasticity, courtship behaviour, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron 45:753–764PubMed

170.

Restivo L, Ferrari F, Passimo E et al (2005) Enriched environment promotes behavioural and morphological recovery in a mouse model for the fragile X syndrome. Proc Natl Acad Sci USA 102:11557–11562

Titel: Fragile X-associated disorders: a clinical overview
verfasst von: Anne Gallagher
Brian Hallahan
Publikationsdatum: 01.03.2012
Verlag: Springer-Verlag
Erschienen in: Journal of Neurology / Ausgabe 3/2012
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-011-6161-3

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Fragile X-associated disorders: a clinical overview

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