Top

Published in:

Open Access 01-12-2011 | Article

Turner syndrome and sexual differentiation of the brain: implications for understanding male-biased neurodevelopmental disorders

Authors: Rebecca Christine Knickmeyer, Marsha Davenport

Published in: Journal of Neurodevelopmental Disorders | Issue 4/2011

Abstract

Turner syndrome (TS) is one of the most common sex chromosome abnormalities. Affected individuals often show a unique pattern of cognitive strengths and weaknesses and are at increased risk for a number of other neurodevelopmental conditions, many of which are more common in typical males than typical females (e.g., autism and attention-deficit hyperactivity disorder). This phenotype may reflect gonadal steroid deficiency, haploinsufficiency of X chromosome genes, failure to express parentally imprinted genes, and the uncovering of X chromosome mutations. Understanding the contribution of these different mechanisms to outcome has the potential to improve clinical care for individuals with TS and to better our understanding of the differential vulnerability to and expression of neurodevelopmental disorders in males and females. In this paper, we review what is currently known about cognition and brain development in individuals with TS, discuss underlying mechanisms and their relevance to understanding male-biased neurodevelopmental conditions, and suggest directions for future research.

Achenbach TM. Manual for the Child Behavior Checklist and 1991 Profile. Burlington: University of Vermont Department of Psychiatry; 1991.

Adem A, Jossan SS, Dargy R, Gillberg PG, Nordberg A, Winblad B, et al. Insulin-like growth factor-I (Igf-1) receptors in the human brain—quantitative autoradiographic localization. Brain Res. 1989;503(2):299–303.PubMed

Albrecht L, Styne D. Laboratory testing of gonadal steroids in children. Pediatr Endocrinol Rev. 2007;5 Suppl 1:599–6097.PubMed

Amundson E, Boman UW, Barrenas ML, Bryman I, Landin-Wilhelmsen K. Impact of growth hormone therapy on quality of life in adults with Turner syndrome. J Clin Endocrinol Metab. 2010;95(3):1355–9.PubMed

Ashworth A, Rastan S, Lovellbadge R, Kay G. X-chromosome inactivation may explain the difference in viability of XO humans and mice. Nature. 1991;351(6325):406–8.PubMed

Baird G, Cox A, Charman T, Baron-Cohen S, Wheelwright S, Swettenham J, et al. A screening instrument for autism at 18 months of age: a six year follow-up study. J Am Acad Child Adolesc Psychiatry. 2000;39:694–702.PubMed

Baird G, Simonoff E, Pickles A, Chandler S, Loucas T, Meldrum D, et al. Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP). Lancet. 2006;368(9531):210–5.PubMed

Bakkaloglu B, O’Roak BJ, Louvi A, Gupta AR, Abelson JE, Morgan TM, et al. Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders. Am J Hum Genet. 2008;82(1):165–73.PubMedCentralPubMed

Beaton EA, Stoddard J, Lai S, Lackey J, Shi JR, Ross JL, et al. Atypical functional brain activation during a multiple object tracking task in girls with Turner syndrome: neurocorrelates of reduced spatiotemporal resolution. Am J Intellect Dev Disabil. 2010;115(2):140–56.PubMedCentralPubMed

Beck KD, Powellbraxton L, Widmer HR, Valverde J, Hefti F. Igf1 Gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons. Neuron. 1995;14(4):717–30.PubMed

Beery K. Development test of visual-motor integration: administration, scoring, and teaching manual, 3rd revision. Cleveland: Modern Curriculum Press; 1989.

Bellinger DC. Are children with congenital cardiac malformations at increased risk of deficits in social cognition? Cardiol Young. 2008;18(1):3–9.PubMed

Benton A, deS Hamsher K, Varney N, Spreen O. Facial recognition test. In: Contributions to Neuropsychological Assessment. New York: Oxford University Press; 1983

Boman UW, Bryman I, Moller A. Psychological well-being in women with Turner syndrome: somatic and social correlates. J Psychosom Obstet Gynecol. 2004;25(3–4):211–9.

Borod JC, Welkowitz J, Alpert M, Brozgold AZ, Martin C, Peselow E, et al. Parameters of emotional processing in neuropsychiatric disorders—conceptual issues and a battery of tests. J Commun Disord. 1990;23(4–5):247–71.PubMed

Brookes KJ, Hawi Z, Kirley A, Barry E, Gill M, Kent L. Association of the steroid sulfatase (STS) gene with attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(8):1531–5.PubMed

Brown WE, Kesler SR, Eliez S, Warsofsy IS, Haberecht M, Patwardhan A, et al. Brain development in Turner syndrome: a magnetic resonance imaging study. Psychiatry Res. 2002;116:187–96.PubMedCentralPubMed

Carey W, McDevitt S. The Carey Temperament Scales. Scottsdale: Behavioral-Developmental Initiatives; 1995.

Carney RM, Wolpert CM, Ravan SA, Shahbazian M, Ashley-Koch A, Cuccaro ML, et al. Identification of MECP2 mutations in a series of females with autistic disorder. Pediatr Neurol. 2003;28(3):205–11.PubMed

Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005;434(7031):400–4.PubMed

Carson MJ, Behringer RR, Brinster RL, Mcmorris FA. Insulin-like growth factor-I increases brain growth and central-nervous-system myelination in transgenic mice. Neuron. 1993;10(4):729–40.PubMed

Chakrabarti S, Fombonne E. Pervasive developmental disorders in preschool children. J Am Med Assoc. 2001;285:3093–9.

Chakrabarti B, Dudbridge F, Kent L, Wheelwright S, Hill-Cawthorne G, Allison C, et al. Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome. Autism Res. 2009;2(3):157–77.PubMed

Christopoulos P, Deligeoroglou E, Laggari V, Christogiorgos S, Creatsas G. Psychological and behavioural aspects of patients with Turner syndrome from childhood to adulthood: a review of the clinical literature. J Psychosom Obstet Gynecol. 2008;29(1):45–51.

Coculescu M. Blood–brain barrier for human growth hormone and insulin-like growth factor-I. J Pediatr Endocrinol Metab. 1999;12(2):113–24.PubMed

Colarusso R, Hammill D. Motor-free Visual Perception Test—revised manual. Novato: Academic Therapy; 1996.

Courant F, Aksglaede L, Antignac JP, Monteau F, Sorensen K, Andersson AM, et al. Assessment of circulating sex steroid levels in prepubertal and pubertal boys and girls by a novel ultrasensitive gas chromatography-tandem mass spectrometry method. J Clin Endocrinol Metab. 2010;95(1):82–92.PubMed

Craig IW, Harper E, Loat CS. The genetic basis for sex differences in human behaviour: role of the sex chromosomes. Ann Hum Genet. 2004;68:269–84.PubMed

Creswell CS, Skuse DH. Autism in association with Turner syndrome: genetic implications for male vulnerability to pervasive developmental disorders. Neurocase. 1999;5:511–8.

Cutter WJ, Daly EM, Robertson DMW, Chitnis XA, van Amelsvoort TAMJ, Simmons A, et al. Influence of X chromosome and hormones on human brain development: a magnetic resonance imaging and proton magnetic resonance spectroscopy study of Turner syndrome. Biol Psychiatry. 2006;59(3):273–83.PubMed

Daoud H, Bonnet-Brilhault F, Vedrine S, Demattei MV, Vourc’h P, Bayou N, et al. Autism and Nonsyndromic Mental retardation associated with a de novo mutation in the NLGN4X gene promoter causing an increased expression level. Biol Psychiatry. 2009;66(10):906–10.PubMed

Davenport ML. Evidence for early initiation of growth hormone and transdermal estradiol therapies in girls with Turner syndrome. Growth Horm IGF Res. 2006;16:S91–7.PubMed

Davenport ML, Quigley CA, Zagar AJ, Grp TTS. Linear growth deteriorates, while head circumference improves in infants and toddlers with Turner syndrome. Pediatr Res. 2002;51(4):115a–a.

Davenport ML, Crowe BJ, Travers SH, Rubin K, Ross JL, Fechner PY, et al. Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multicenter trial. J Clin Endocrinol Metab. 2007;92(9):3406–16.PubMed

Davenport ML, Roush J, Liu C, Zagar AJ, Eugster E, Travers S, et al. Growth hormone treatment does not affect incidences of middle ear disease or hearing loss in infants and toddlers with Turner syndrome. Horm Res Paediatr. 2010;74:23–32.PubMedCentralPubMed

Davies W, Wilkinson LS. It is not all hormones: alternative explanations for sexual differentiation of the human brain. Brain Res. 2006;1126:36–45.PubMed

Davies W, Isles A, Smith R, Karunadasa D, Burrmann D, Humby T, et al. Xlr3b is a new imprinted candidate for X-linked parent-of-origin effects on cognitive function in mice. Nat Genet. 2005;37(6):625–9.PubMed

Davies W, Humby T, Isles AR, Burgoyne PS, Wilkinson LS. X-monosomy effects on visuospatial attention in mice: a candidate gene and implications for Turner syndrome and attention deficit hyperactivity disorder. Biol Psychiatry. 2007;61(12):1351–60.PubMed

De Vries G, Simerly RB. Anatomy, development, and function of sexually dimorphic neural circuits in the mammalian brain. In: Pfaff D, Arnold A, Etgen A, Fahrbach S, Rubin R, editors. Hormones, Brain and Behavior. New York: Academic; 2002. p. 137–91.

De Vries GJ, Rissman EF, Simerly RB, Yang L, Scordalakes EM, Auger CJ, et al. A model system for study of sex chromosome effects of sexually dimorphic neural and behavioral traits. J Neurosci. 2002;22(20):9005–14.PubMed

Denman S. Neuropsychology memory scale. Charleston: S Denman; 1984.

Dobkin C, Radu G, Ding XH, Brown WT, Nolin SL. Fragile X prenatal analyses show full mutation females at high risk for mosaic Turner syndrome: fragile X leads to chromosome loss. Am J Med Genet A. 2009;149A(10):2152–7.PubMed

Doherty MJ, Glass IA, Bennett CL, Cotter PD, Watson NF, Mitchell AL, et al. An Xp; Yq translocation causing a novel contiguous gene syndrome in brothers with generalized epilepsy, ichthyosis, and attention deficits. Epilepsia. 2003;44(12):1529–35.PubMed

Elia J, Gai X, Xie H, Perin J, Geiger E, Glessner J, et al. Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes. Mol Psychiatry. 2010;15(6):637–46.PubMedCentralPubMed

Elliott TK, Watkins JM, Messa C, Lippe B, Chugani H. Positron emission tomography and neuropsychological correlations in children with Turner’s syndrome. Dev Neuropsychol. 1996;12(3):365–86.

Fechner PY, Davenport ML, Qualy RL, Ross JL, Gunther DF, Eugster EA, et al. Differences in follicle-stimulating hormone secretion between 45, X monosomy Turner syndrome and 45, X/46, XX mosaicism are evident at an early age. J Clin Endocrinol Metab. 2006;91(12):4896–902.PubMed

Feng JN, Schroer R, Yan J, Song WJ, Yang CM, Bockholt A, et al. High frequency of neurexin 1 beta signal peptide structural variants in patients with autism. Neurosci Lett. 2006;409(1):10–3.PubMed

Fombonne E. The changing epidemiology of autism. J Appl Res Intellect Disabil. 2005;18(4):281–94.

Friedman JI, Vrijenhoek T, Markx S, Janssen IM, Van der Vliet WA, Faas BHW, et al. CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy. Mol Psychiatry. 2008;13(3):261–6.PubMed

Good CD, Lawrence K, Thomas NS, Price CJ, Ashburner J, Friston KJ, et al. Dosage-sensitive X-linked locus influences the development of amygdala and orbitofrontal cortex, and fear recognition in humans. Brain. 2003;126:2431–46.PubMed

Grumbach MM, Auchus RJ. Commentary—estrogen consequences and implications of human mutations in synthesis and action. J Clin Endocrinol Metab. 1999;84(12):4677–94.PubMed

Gullotta F, Rehder H. Chromosomal anomalies and central nervous-system. Beitrage Zur Pathologie. 1974;152(1):74–80.PubMed

Gunnell D, Miller LL, Rogers I, Holly JMP, Team AS. Association of insulin-like growth factor I and insulin-like growth factor-binding protein-3 with intelligence quotient among 8- to 9-year-old children in the Avon longitudinal study of parents and children. Pediatrics. 2005;116(5):E681–6.PubMed

Haaland KY, Delaney HD. Motor deficits after left or right-hemisphere damage due to stroke or tumor. Neuropsychologia. 1981;19(1):17–27.PubMed

Haberecht MF, Menon V, Warsofsky IS, White CD, Dyer-Friedman J, Glover GH, et al. Functional neuroanatomy of visuo-spatial working memory in Turner syndrome. Hum Brain Mapp. 2001;14(2):96–107.PubMed

Hart SJ, Davenport ML, Hooper SR, Belger A. Visuospatial executive function in Turner syndrome: functional MRI and neurocognitive findings. Brain. 2006;129:1125–36.PubMed

Hazlett HC, Poe M, Gerig G, Smith RG, Provenzale J, Ross A, et al. Magnetic resonance imaging and head circumference study of brain size in autism—birth through age 2 years. Arch Gen Psychiatry. 2005;62(12):1366–76.PubMed

Henn W, Zhang KD. Mosaicism in Turner’s syndrome. Nature. 1997;390:569.PubMed

Hines M. Sexual differentiation of human brain and behavior. In: Pfaff D, Arnold A, Etgen A, Fahrbach S, Rubin R, editors. Hormones, Brain and Behavior. New York: Academic; 2002. p. 425–62.

Holzapfel M, Barnea-Goraly N, Eckert MA, Kesler SR, Reiss AL. Selective alterations of white matter associated with visuospatial and sensorimotor dysfunction in Turner syndrome. J Neurosci. 2006;26(26):7007–13.PubMedCentralPubMed

Hooper SR, Davenport ML, Ross JL. Neurocognitive and psychosocial dysfunction in preschool children with Turner syndrome. In: 113th Annual Convention of the American Psychological Association. Washington; 2005.

Hultcrantz M. Ear and hearing problems in Turner’s syndrome. Acta Otolaryngol. 2003;123(2):253–7.PubMed

Jacobs PA, Melville M, Ratcliff S, Keay AJ, Syme J. Cytogenetic survey of 11,680 newborn-infants. Ann Hum Genet. 1974;37(4):359–76.PubMed

Jamain S, Quach H, Betancur C, Rastam M, Colineaux C, Gillberg IC, et al. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet. 2003;34(1):27–9.PubMedCentralPubMed

Johnston CM, Lovell FL, Leongamornlert DA, Stranger BE, Dermitzakis ET, Ross MT. Large-scale population study of human cell lines indicates that dosage compensation is virtually complete. PloS Genet. 2008;4(1): e9. doi:10.1371/journal.pgen.0040009

Kagan J. Reflection-impulsivity—generality and dynamics of conceptual tempo. J Abnorm Psychol. 1966;71(1):17–27.PubMed

Kaufman A. K-ABC Assessment Battery for Children. Circle Pines: American Guidance Service; 1983.

Kawanishi C, Kono M, Onishi H, Ishii N, Ishii K. A case of Turner syndrome with schizophrenia: genetic relationship between Turner syndrome and psychosis. Psychiatry Clin Neurosci. 1997;51(2):83–5.PubMed

Kent L, Emerton J, Bhadravathi V, Weisblatt E, Pasco G, Willatt LR, et al. X-linked ichthyosis (steroid sulfatase deficiency) is associated with increased risk of attention deficit hyperactivity disorder, autism and social communication deficits. J Med Genet. 2008;45(8):519–24.PubMed

Kesler SR, Blasey CM, Brown WE, Yankowitz J, Zeng SM, Bender BG, et al. Effects of X-monosomy and X-linked imprinting on superior temporal gyrus morphology in Turner syndrome. Biol Psychiatry. 2003;54:636–46.PubMedCentralPubMed

Kesler SR, Garrett A, Bender B, Yankowitz J, Zeng SM, Reiss AL. Amygdala and hippocampal volumes in Turner syndrome: a high-resolution MRI study of X-monosomy. Neuropsychologia. 2004;42(14):1971–8.PubMedCentralPubMed

Kesler SR, Menon V, Reiss AL. Neurofunctional differences associated with arithmetic processing in Turner syndrome. Cereb Cortex. 2006;16(6):849–56.PubMedCentralPubMed

Kim HG, Kishikawa S, Higgins AW, Seong IS, Donovan DJ, Shen Y, et al. Disruption of neurexin 1 associated with autism spectrum disorder. Am J Hum Genet. 2008;82(1):199–207.PubMedCentralPubMed

Kirov G, Gumus D, Chen W, Norton N, Georgieva L, Sari M, et al. Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Hum Mol Genet. 2008;17(3):458–65.PubMed

Kirov G, Grozeva D, Norton N, Ivanov D, Mantripragada KK, Holmans P, et al. Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. Hum Mol Genet. 2009;18(8):1497–503.PubMedCentralPubMed

Klein KO, Baron J, Colli MJ, Mcdonnell DP, Cutler GB. Estrogen-levels in childhood determined by an ultrasensitive recombinant cell bioassay. J Clin Investig. 1994;94(6):2475–80.PubMedCentralPubMed

Kubota T, Wakui K, Nakamura T, Ohashi H, Watanabe Y, Yoshino M, et al. The proportion of cells with functional X disomy is associated with the severity of mental retardation in mosaic ring X Turner syndrome females. Cytogenet Genome Res. 2002;99(1–4):276–84.PubMed

Kulkarni J. Oestrogen—a new treatment approach for schizophrenia? Med J Australia. 2009;190(4):S37–8.PubMed

Lam C, Yeung W, Ko C, Poon P, Tong S, Chan K, et al. Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome. J Med Genet. 2000;37:E41.PubMedCentralPubMed

Laumonnier F, Bonnet-Brihault F, Gomot M, Blanc R, David A, Moizard M, et al. X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet. 2004;74:552–7.PubMedCentralPubMed

Lawson-Yuen A, Saldivar JS, Sommer S, Picker J. Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur J Hum Genet. 2008;16(5):614–8.PubMed

Leone P, Comoletti D, Ferracci G, Conrod S, Garcia SU, Taylor P, et al. Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions. EMBO J. 2010;29(14):2461–71.PubMedCentralPubMed

Liederman J, Kantrowitz L, Flannery K. Male vulnerability to reading disability is not likely to be a myth: a call for new data. J Learn Disabil. 2005;38(2):109–29.PubMed

Livadas S, Xekouki P, Fouka F, Kanaka-Gantenbein C, Kaloumenou I, Mavrou A, et al. Prevalence of thyroid dysfunction in Turner’s syndrome: a long-term follow-up study and brief literature review. Thyroid. 2005;15(9):1061–6.PubMed

Lord C, Schopler E, Revicki D. Sex-differences in autism. J Autism Dev Disord. 1982;12(4):317–30.PubMed

Majewska MD. Neurosteroids—endogenous bimodal modulators of the GABA-A receptor—mechanism of action and physiological significance. Prog Neurobiol. 1992;38(4):379–95.PubMed

McCarney D. Test of Variables of Attention (TOVA). St. Paul: Attention Technology; 1990.

Mccarthy MM. Molecular aspects of sexual-differentiation of the rodent brain. Psychoneuroendocrinology. 1994;19(5–7):415–27.PubMed

McCarthy MM, Amateau SK, Mong JA. Steroid modulation of astrocytes in the neonatal brain: implications for adult reproductive function. Biol Reprod. 2002;67(3):691–8.PubMed

McQuillen PS, Miller SP. Congenital heart disease and brain development. Year in Neurology 2. 2010;1184:68–86.

Menke LA, Sas TCJ, Visser M, Kreukels BPC, Stijnen T, Zandwijken GRJ, et al. The effect of the weak androgen oxandrolone on psychological and behavioral characteristics in growth hormone-treated girls with Turner syndrome. Horm Behav. 2010;57(3):297–305.PubMed

Moffitt TE. Juvenile-delinquency and attention deficit disorder—boys developmental trajectories from age 3 to age 15. Child Dev. 1990;61(3):893–910.PubMed

Moffitt TE, Caspi A. Childhood predictors differentiate life-course persistent and adolescence-limited antisocial pathways among males and females. Dev Psychopathol. 2001;13(2):355–75.PubMed

Molko N, Cachia A, Riviere D, Mangin JF, Bruandet M, Le Bihan D, et al. Functional and structural alterations of the intraparietal sulcus in a developmental dyscalculia of genetic origin. Neuron. 2003;40(4):847–58.PubMed

Molko N, Cachia A, Riviere D, Mangin JF, Bruandet M, LeBihan D, et al. Brain anatomy in Turner syndrome: evidence for impaired social and spatial-numerical networks. Cereb Cortex. 2004;14(8):840–50.PubMed

Molland EA, Purcell M. Biliary atresia and Dandy–Walker anomaly in a neonate with 45,X Turners syndrome. J Pathol. 1975;115(4):227.PubMed

Money J, Alexander D, Walker H. A standardized road map of directional sense. Baltimore: Johns Hopkins Press; 1965.

Mors O, Mortensen PB, Ewald H. No evidence of increased risk for schizophrenia or bipolar affective disorder in persons with aneuploidies of the sex chromosomes. Psychol Med. 2001;31(3):425–30.PubMed

Mortensen KH, Cleemann L, Hjerrild BE, Nexo E, Locht H, Jeppesen EM, et al. Increased prevalence of autoimmunity in Turner syndrome—influence of age. Clin Exp Immunol. 2009;156(2):205–10.PubMedCentralPubMed

Mullen EM. Mullens Scales of Early Development. Circle Pines: American Guidance Service Inc.; 1995.

Need AC, Ge DL, Weale ME, Maia J, Feng S, Heinzen EL, et al. A genome-wide investigation of SNPs and CNVs in schizophrenia. Plos Genetics. 2009;5(2):e1000373.PubMedCentralPubMed

Nelson HD, Nygren P, Walker M, Panoscha R. Screening for speech and language delay in preschool children: systematic evidence review for the US preventive services task force. Pediatrics. 2006;117(2):E298–319.PubMed

Nielsen J, Wohlert M. Chromosome-abnormalities found among 34910 newborn children—results from a 13-year incidence study in Arhus, Denmark. Hum Genet. 1991;87(1):81–3.PubMed

Noor A, Whibley A, Marshall CR, Gianakopoulos PJ, Piton A, Carson AR, et al. Disruption at the PTCHD1 locus on Xp22.11 in autism spectrum disorder and intellectual disability. Sci Transl Med. 2010;2(49):49–68.

Nyberg F. Growth hormone in the brain: characteristics of specific brain targets for the hormone and their functional significance. Front Neuroendocrinol. 2000;21(4):330–48.PubMed

Pasquino AM, Passeri F, Pucarelli I, Segni M, Municchi G. Spontaneous pubertal development in Turner’s syndrome. J Clin Endocrinol Metab. 1997;82(6):1810–3.PubMed

Pinto D et al. Functional impact of global rare copy number variation in autism spectrum conditions. Nature. 2010;466(7304):368–72.PubMedCentralPubMed

Prior TI, Chue PS, Tibbo P. Investigation of Turner syndrome in schizophrenia. Am J Med Genet. 2000;96(3):373–8.PubMed

Qi HB, Xing LX, Zhan KJ, Gao XC, Zheng ZJ, Huang SP, et al. Positive association of neuroligin-4 gene with nonspecific mental retardation in the Qinba Mountains Region of China. Psychiatr Genet. 2009;19(1):1–5.PubMed

Rae C, Joy P, Harasty J, Kemp A, Kuan S, Christodoulou J, et al. Enlarged temporal lobes in Turner syndrome: an X-chromosome effect? Cereb Cortex. 2004;14(2):156–64.PubMed

Rahhal SN, Fuqua JS, Lee PA. The impact of assay sensitivity in the assessment of diseases and disorders in children. Steroids. 2008;73(13):1322–7.PubMed

Ranke MB, Grauer ML. Adult height in Turner syndrome—results of a multinational survey 1993. Horm Res. 1994;42(3):90–4.PubMed

Rao E, Weiss B, Fukami M, Rump A, Niesler B, Mertz A, et al. Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nat Genet. 1997;16(1):54–63.PubMed

Rasika S, Alvarez-Buylla A, Nottebohm F. BDNF mediates the effects of testosterone on the survival of new neurons in an adult brain. Neuron. 1999;22(1):53–62.PubMed

Reisert I, Pilgrim C. Sexual-differentiation of monoaminergic neurons—genetic or epigenetic. Trends Neurosci. 1991;14(10):468–73.PubMed

Reskenielsen E, Christensen AL, Nielsen J. A neuropathological and neuropsychological study of Turners syndrome. Cortex. 1982;18(2):181–90.

Romans SM, Stefanatos G, Roeltgen DP, Kushner H, Ross JL. Transition to young adulthood in Ullrich–Turner syndrome: neurodevelopmental changes. Am J Med Genet. 1998;79(2):140–7.PubMed

Roser P, Kawohl W. Turner syndrome and schizophrenia: a further hint for a role of the X-chromosome in the pathogenesis of schizophrenic disorders. World J Biol Psychiatry. 2010;11(2):239–42.PubMed

Ross JL, Roeltgen D, Feuillan P, Kushner H, Cutler GB. Effects of estrogen on nonverbal processing speed and motor function in girls with Turner’s syndrome. J Clin Endocrinol Metab. 1998;83(9):3198–204.PubMed

Ross JL, Roeltgen D, Feuillan P, Kushner H, Cutler GB. Use of estrogen in young girls with Turner syndrome—effects on memory. Neurology. 2000a;54(1):164–70.PubMed

Ross JL, Roeltgen D, Kushner H, Wei FL, Zinn AR. The Turner syndrome-associated neurocognitive phenotype maps to distal Xp. Am J Hum Genet. 2000b;67(3):672–81.PubMedCentralPubMed

Ross JL, Stefenatos GA, Kushner H, Zinn A, Bondy C, Roeltgen D. Persistent cognitive deficits in adult women with Turner syndrome. Neurology. 2002;58(2):218–25.PubMed

Ross JL, Roeltgen D, Stefanatos GA, Feuillan P, Kushner H, Bondy C, et al. Androgen-responsive aspects of cognition in girls with Turner syndrome. J Clin Endocrinol Metab. 2003;88(1):292–6.PubMed

Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, et al. The DNA sequence of the human X chromosome. Nature. 2005;434(7031):325–37.PubMedCentralPubMed

Ross J, Roeltgen D, Zinn A. Cognition and the sex chromosomes: studies in Turner syndrome. Horm Res. 2006;65(1):47–56.PubMed

Rossi E, Verri AP, Patricelli MG, Destefani V, Ricca I, Vetro A, et al. A 12 Mb deletion at 7q33-q35 associated with autism spectrum disorders and primary amenorrhea. Eur J Med Genet. 2008;51(6):631–8.PubMed

Rovet J. Turner syndrome: a review of genetic and hormonal influences on neuropsychological functioning. Child Neuropsychol. 2004;10(4):262–79.PubMed

Rujescu D, Ingason A, Cichon S, Pietilainen OPH, Barnes MR, Toulopoulou T, et al. Disruption of the neurexin 1 gene is associated with schizophrenia. Hum Mol Genet. 2009;18(5):988–96.PubMedCentralPubMed

Russell HF, Wallis D, Mazzocco MMM, Moshang T, Zackai E, Zinn AR, et al. Increased prevalence of ADHD in Turner syndrome with no evidence of imprinting effects. J Pediatr Psychol. 2006;31(9):945–55.PubMed

Rutter M, Caspi A, Moffitt TE. Using sex differences in psychopathology to study causal mechanisms: unifying issues and research strategies. J Child Psychol Psychiatry Allied Disciplines. 2003;44(8):1092–115.

Saenger P, Wikland KA, Conway GS, Davenport M, Gravholt CH, Hintz R, et al. Recommendations for the diagnosis and management of Turner syndrome. J Clin Endocrinol Metab. 2001;86(7):3061–9.PubMed

Sagi L, Zuckerman-Levin N, Gawlik A, Ghizzoni L, Buyukgebiz A, Rakover Y, et al. Clinical significance of the parental origin of the X chromosome in Turner syndrome. J Clin Endocrinol Metab. 2007;92(3):846–52.PubMed

Salameh EK, Nettelbladt U, Gullberg B. Risk factors for language impairment in Swedish bilingual and monolingual children relative to severity. Acta Paediatr. 2002;91(12):1379–84.PubMed

Sandberg DE, Voss LD. The psychosocial consequences of short stature: a review of the evidence. Best Pract Res Clin Endocrinol Metab. 2002;16(3):449–63.PubMed

Savendahl L, Davenport ML. Delayed diagnoses of Turner’s syndrome: proposed guidelines for change. J Pediatr. 2000;137(4):455–9.PubMed

Schmitt A, Parlapani E, Bauer M, Heinsen H, Falkai P. Is brain banking of psychiatric cases valuable for neurobiological research? Clinics. 2008;63(2):255–66.PubMedCentralPubMed

Shinawi M, Patel A, Panichkul P, Zascavage R, Peters SU, Scaglia F. The Xp contiguous deletion syndrome and autism. Am J Med Genet A. 2009;149A(6):1138–48.PubMed

Simerly RB. Wired for reproduction: organization and development of sexually dimorphic circuits in the mammalian forebrain. Annu Rev Neurosci. 2002;25:507–36.PubMed

Skuse DH. Imprinting, the X-chromosome, and the male brain: explaining sex differences in the liability to autism. Pediatr Res. 2000;47:9–16.PubMed

Skuse DH, James RS, Bishop DVM, Coppins B, Dalton P, Aamondt-Leeper G, et al. Evidence from Turner’s syndrome of an imprinted X-linked locus affecting cognitive function. Nature. 1997;387(12):705–8.PubMed

Skuse DH, Morris JS, Dolan RJ. Functional dissociation of amygdala-modulated arousal and cognitive appraisal, in Turner syndrome. Brain. 2005;128:2084–96.PubMed

Sparrow S, Balla DA. Vineland Social-Emotional Early Childhood Scales. Circle Pines: American Guidance Service; 1998.

Stone JL, O’Donovan MC, Gurling H, Kirov GK, Blackwood DHR, Corvin A, et al. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature. 2008;455(7210):237–41.

Sumner BEH, Fink G. Testosterone as well as estrogen increases serotonin(2A) receptor mRNA and binding site densities in the male rat brain. Mol Brain Res. 1998;59(2):205–14.PubMed

Sybert VP. Cardiovascular malformations and complications in Turner syndrome. Pediatrics. 1998;101:1–7.

Sybert VP, McCauley E. Turner’s syndrome. N Engl J Med. 2004;351(12):1227–38.PubMed

Szatmari P, Offord DR, Boyle MH. Ontario Child Health Study—prevalence of attention deficit disorder with hyperactivity. J Child Psychol Psychtr Allied Disc. 1989;30(2):219–30.

Szatmari P, Paterson AD, Zwaigenbaum L, Roberts W, Brian J, Liu XQ, et al. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet. 2007;39(3):319–28.PubMed

Talebizadeh Z, Lam DY, Theodoro MF, Bittel DC, Lushington GH, Butler MG. Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism. J Med Genet. 2006;43(5):e21.PubMedCentralPubMed

Thornton J, Zehr JL, Loose MD. Effects of prenatal androgens on rhesus monkeys: a model system to explore the organizational hypothesis in primates. Horm Behav. 2009;55(5):633–44.PubMedCentralPubMed

Tucker DM, Roeltgen MG, Roeltgen DP, Kline R, Kline J. Dyslexia and impaired phonological memory. J Clin Exp Neuropsychol. 1974;11(26):Abstract

Urich H. Cerebellar malformations: Some pathogenetic considerations. Clin Exp Neurol. 1979;16:119031.

Waber DP, Holmes JM. Assessing children’s copy productions of the Rey–Osterrieth complex figure. J Clin Exp Neuropsychol. 1985;7(3):264–80.PubMed

Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM, et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science. 2008;320(5875):539–43.PubMed

Wang HS, Kuo MF. Tourette’s syndrome in Taiwan: an epidemiological study of tic disorders in an elementary school at Taipei County. Brain Dev. 2003;25:S29–31.PubMed

Wang ZX, Bullock NA, Devries GJ. Sexual-differentiation of vasopressin projections of the bed nucleus of the stria terminals and medial amygdaloid nucleus in rats. Endocrinology. 1993;132(6):2299–306.PubMed

Warrington E. Recognition Memory Test. Windsor: Nfer-Nelson Publishing Company; 1984.

Warrington E, James M. The visual object and perception battery. Suffolk: Thames Valley Test Company; 1991.

Wechsler D. Wechsler Intelligence Scale for Children—revised. San Antonio: Psychological Corporation; 1974.

Wechsler D. Wechsler Memory Scale—revised manual. San Antonio: The Psychological Corporation; 1987.

Weiss LA, Purcell S, Waggoner S, Lawrence K, Spektor D, Daly MJ, et al. Identification of EFHC2 as a quantitative trait locus for fear recognition in Turner syndrome. Hum Mol Genet. 2007;16(1):107–13.PubMed

Williams GR. Neurodevelopmental and neurophysiological actions of thyroid hormone. J Neuroendocrinol. 2008;20(6):784–94.PubMed

Yan J, Oliveira G, Coutinho A, Yang C, Feng J, Katz C, et al. Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients. Mol Psychiatry. 2005;10(4):329–32.PubMed

Yang LY, Verhovshek T, Sengelaub DR. Brain-derived neurotrophic factor and androgen interact in the maintenance of dendritic morphology in a sexually dimorphic rat spinal nucleus. Endocrinology. 2004;145(1):161–8.PubMed

Zhang JM, Konkle ATM, Zup SL, McCarthy MM. Impact of sex and hormones on new cells in the developing rat hippocampus: a novel source of sex dimorphism? Eur J Neurosci. 2008;27(4):791–800.PubMedCentralPubMed

Zinn AR, Roeltgen D, Stefanatos G, Ramos P, Elder FF, Kushner H, et al. A Turner syndrome neurocognitive phenotype maps to Xp22.3. Behav Brain Funct. 2007;3:24.PubMedCentralPubMed

Zinn AR, Kushner H, Ross JL. EFHC2 SNP rs7055196 is not associated with fear recognition in 45, X Turner syndrome. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(4):507–9.PubMed

Zuckerman-Levin N, Frolova-Bishara T, Militianu D, Levin M, Aharon-Peretz J, Hochberg Z. Androgen replacement therapy in Turner syndrome: a pilot study. J Clin Endocrinol Metab. 2009;94(12):4820–7.PubMed

Zweier C, de Jong E, Zweier M, Orrico A, Ousager L, Collins A, et al. CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt–Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila. Am J Hum Genet. 2009;85(5):655–66.PubMedCentralPubMed

Title: Turner syndrome and sexual differentiation of the brain: implications for understanding male-biased neurodevelopmental disorders
Authors: Rebecca Christine Knickmeyer
Marsha Davenport
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Journal of Neurodevelopmental Disorders / Issue 4/2011
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI: https://doi.org/10.1007/s11689-011-9089-0

At a glance: The STEP trials

Springer Medicine

Turner syndrome and sexual differentiation of the brain: implications for understanding male-biased neurodevelopmental disorders

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2011

Epigenetic modifications may play a role in the developmental consequences of early life events

Genetics and language: a neurobiological perspective on the missing link (-ing hypotheses)

Dissection of genetic associations with language-related traits in population-based cohorts

Language development after cochlear implantation: an epigenetic model

Repetitive behavior profiles: Consistency across autism spectrum disorder cohorts and divergence from Prader–Willi syndrome

Approach to epigenetic analysis in language disorders