Clinical Neurogenetics: Autism Spectrum Disorders

Neurologic Clinics

Volumn 31, Issue 4, 2013, Pages 951-968

  Mehta, Sunil Q ^a   Golshani, Peyman ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Autism; Autism spectrum disorders; Chromosomal microarray; Genetic testing

Indexed keywords

ARIPIPRAZOLE; FLUOXETINE; FLUVOXAMINE; METHYLPHENIDATE; RISPERIDONE;

ASPERGER SYNDROME; AUTISM; BEHAVIOR; COMORBIDITY; COMPULSION; DIFFERENTIAL DIAGNOSIS; DISEASE COURSE; FUNCTIONAL DISEASE; GENETIC SCREENING; HUMAN; LANGUAGE DELAY; MICROARRAY ANALYSIS; PATHOPHYSIOLOGY; PERVASIVE DEVELOPMENTAL DISORDER NOT OTHERWISE SPECIFIED; PRIORITY JOURNAL; RETT SYNDROME; REVIEW; SOCIAL INTERACTION; SYMPTOMATOLOGY;

AUTISM; AUTISM SPECTRUM DISORDERS; CHROMOSOMAL MICROARRAY; GENETIC TESTING;

CHILD DEVELOPMENT DISORDERS, PERVASIVE; GENETIC TESTING; HUMANS; MICROARRAY ANALYSIS;

EID: 84886418133     PISSN: 07338619     EISSN: 15579875     Source Type: Journal    
DOI: 10.1016/j.ncl.2013.04.009     Document Type: Review

References (120)

1. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators, Centers for Disease Control and Prevention Prevalence of autism spectrum disorders-Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ 2012, 61(3):1-19.
2. Bryson S.E., Zwaigenbaum L., McDermott C., et al. The Autism Observation Scale for Infants: scale development and reliability data. JAutism Dev Disord 2008, 38(4):731-738.
3. Wolff J.J., Gu H., Gerig G., et al. Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. Am J Psychiatry 2012, 169(6):589-600.
4. Kotagal S., Broomall E. Sleep in children with autism spectrum disorder. Pediatr Neurol 2012, 47(4):242-251.
5. Fombonne E., Roge B., Claverie J., et al. Microcephaly and macrocephaly in autism. JAutism Dev Disord 1999, 29(2):113-119.
6. Lainhart J.E., Bigler E.D., Bocian M., et al. Head circumference and height in autism: a study by the Collaborative Program of Excellence in Autism. Am J Med Genet A 2006, 140(21):2257-2274.
7. Courchesne E., Carper R., Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. JAMA 2003, 290(3):337-344.
8. Hazlett H.C., Poe M., Gerig G., 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):1366-1376.
9. Bolton P.F., Carcani-Rathwell I., Hutton J., et al. Epilepsy in autism: features and correlates. Br J Psychiatry 2011, 198(4):289-294.
10. Tuchman R., Rapin I. Epilepsy in autism. Lancet Neurol 2002, 1(6):352-358.
11. Ibrahim S.H., Voigt R.G., Katusic S.K., et al. Incidence of gastrointestinal symptoms in children with autism: a population-based study. Pediatrics 2009, 124(2):680-686.
12. Charman T., Pickles A., Simonoff E., et al. IQ in children with autism spectrum disorders: data from the Special Needs and Autism Project (SNAP). Psychol Med 2011, 41(3):619-627.
13. Icasiano F., Hewson P., Machet P., et al. Childhood autism spectrum disorder in the Barwon region: a community based study. JPaediatr Child Health 2004, 40(12):696-701.
14. Kawamura Y., Takahashi O., Ishii T. Reevaluating the incidence of pervasive developmental disorders: impact of elevated rates of detection through implementation of an integrated system of screening in Toyota, Japan. Psychiatry Clin Neurosci 2008, 62(2):152-159.
15. Joshi G., Wozniak J., Petty C., et al. Psychiatric comorbidity and functioning in aclinically referred population of adults with autism spectrum disorders: a comparative study. JAutism Dev Disord 2013, 43(6):1314-1325.
16. Lampi K.M., Lehtonen L., Tran P.L., et al. Risk of autism spectrum disorders in low birth weight and small for gestational age infants. JPediatr 2012, 161(5):830-836.
17. Chess S. Autism in children with congenital rubella. JAutism Child Schizophr 1971, 1(1):33-47.
18. Deykin E.Y., MacMahon B. Viral exposure and autism. Am J Epidemiol 1979, 109(6):628-638.
19. Croen L.A., Najjar D.V., Fireman B., et al. Maternal and paternal age and risk of autism spectrum disorders. Arch Pediatr Adolesc Med 2007, 161(4):334-340.
20. Durkin M.S., Maenner M.J., Newschaffer C.J., et al. Advanced parental age and the risk of autism spectrum disorder. Am J Epidemiol 2008, 168(11):1268-1276.
21. Shelton J.F., Tancredi D.J., Hertz-Picciotto I. Independent and dependent contributions of advanced maternal and paternal ages to autism risk. Autism Res 2010, 3(1):30-39.
22. Retraction-Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 2010, 375(9713):445.
23. Deer B. How the case against the MMR vaccine was fixed. BMJ 2011, 342:c5347.
24. Wakefield A.J., Murch S.H., Anthony A., et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 1998, 351(9103):637-641.
25. Baird G., Pickles A., Simonoff E., et al. Measles vaccination and antibody response in autism spectrum disorders. Arch Dis Child 2008, 93(10):832-837.
26. Honda H., Shimizu Y., Rutter M. No effect of MMR withdrawal on the incidence of autism: a total population study. JChild Psychol Psychiatry 2005, 46(6):572-579.
27. Smeeth L., Cook C., Fombonne E., et al. MMR vaccination and pervasive developmental disorders: a case-control study. Lancet 2004, 364(9438):963-969.
28. Uno Y., Uchiyama T., Kurosawa M., et al. The combined measles, mumps, and rubella vaccines and the total number of vaccines are not associated with development of autism spectrum disorder: the first case-control study in Asia. Vaccine 2012, 30(28):4292-4298.
29. Hallmayer J., Cleveland S., Torres A., et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 2011, 68(11):1095-1102.
30. Lichtenstein P., Carlstrom E., Rastam M., et al. The genetics of autism spectrum disorders and related neuropsychiatric disorders in childhood. Am J Psychiatry 2010, 167(11):1357-1363.
31. Ozonoff S., Young G.S., Carter A., et al. Recurrence risk for autism spectrum disorders: a Baby Siblings Research Consortium Study. Pediatrics 2011, 128(3):e488-e495.
32. Zufferey F., Sherr E.H., Beckmann N.D., et al. A600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders. JMed Genet 2012, 49(10):660-668.
33. Badner J.A., Gershon E.S. Regional meta-analysis of published data supports linkage of autism with markers on chromosome 7. Mol Psychiatry 2002, 7(1):56-66.
34. Cantor R.M., Kono N., Duvall J.A., et al. Replication of autism linkage: fine-mapping peak at 17q21. Am J Hum Genet 2005, 76(6):1050-1056.
35. Wang K., Zhang H., Ma D., et al. Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature 2009, 459(7246):528-533.
36. Klei L., Sanders S.J., Murtha M.T., et al. Common genetic variants, acting additively, are a major source of risk for autism. Mol Autism 2012, 3(1):9.
37. Marshall C.R., Noor A., Vincent J.B., et al. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 2008, 82(2):477-488.
38. Sebat J., Lakshmi B., Malhotra D., et al. Strong association of de novo copy number mutations with autism. Science 2007, 316(5823):445-449.
39. Levy D., Ronemus M., Yamrom B., et al. Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron 2011, 70(5):886-897.
40. Pinto D., Pagnamenta A.T., Klei L., et al. Functional impact of global rare copy number variation in autism spectrum disorders. Nature 2010, 466(7304):368-372.
41. Sanders S.J., Ercan-Sencicek A.G., Hus V., et al. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 2011, 70(5):863-885.
42. Sanders S.J., Murtha M.T., Gupta A.R., et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 2012, 485(7397):237-241.
43. O'Roak B.J., Vives L., Girirajan S., et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 2012, 485(7397):246-250.
44. Courchesne E., Karns C.M., Davis H.R., et al. Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology 2001, 57(2):245-254.
45. Schumann C.M., Bloss C.S., Barnes C.C., et al. Longitudinal magnetic resonance imaging study of cortical development through early childhood in autism. JNeurosci 2010, 30(12):4419-4427.
46. Schumann C.M., Barnes C.C., Lord C., et al. Amygdala enlargement in toddlers with autism related to severity of social and communication impairments. Biol Psychiatry 2009, 66(10):942-949.
47. Thomas M.S., Knowland V.C., Karmiloff-Smith A. Mechanisms of developmental regression in autism and the broader phenotype: a neural network modeling approach. Psychol Rev 2011, 118(4):637-654.
48. Courchesne E., Campbell K., Solso S. Brain growth across the life span in autism: age-specific changes in anatomical pathology. Brain Res 2011, 1380:138-145.
49. O'Roak B.J., Vives L., Fu W., et al. Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science 2012, 338(6114):1619-1622.
50. Courchesne E., Mouton P.R., Calhoun M.E., et al. Neuron number and size in prefrontal cortex of children with autism. JAMA 2011, 306(18):2001-2010.
51. Eyler L.T., Pierce K., Courchesne E. Afailure of left temporal cortex to specialize for language is an early emerging and fundamental property of autism. Brain 2012, 135(Pt 3):949-960.
52. Ritvo E.R., Freeman B.J., Scheibel A.B., et al. Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC Autopsy Research Report. Am J Psychiatry 1986, 143(7):862-866.
53. Fatemi S.H., Halt A.R., Realmuto G., et al. Purkinje cell size is reduced in cerebellum of patients with autism. Cell Mol Neurobiol 2002, 22(2):171-175.
54. Wisniewski K.E., Segan S.M., Miezejeski C.M., et al. The Fra(X) syndrome: neurological, electrophysiological, and neuropathological abnormalities. Am J Med Genet 1991, 38(2-3):476-480.
55. Morgan J.T., Chana G., Abramson I., et al. Abnormal microglial-neuronal spatial organization in the dorsolateral prefrontal cortex in autism. Brain Res 2012, 1456:72-81.
56. Morgan J.T., Chana G., Pardo C.A., et al. Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism. Biol Psychiatry 2010, 68(4):368-376.
57. Vargas D.L., Nascimbene C., Krishnan C., et al. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005, 57(1):67-81.
58. Lord C., Rutter M., Goode S., et al. Autism diagnostic observation schedule: a standardized observation of communicative and social behavior. JAutism Dev Disord 1989, 19(2):185-212.
59. Lord C., Rutter M., Le Couteur A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. JAutism Dev Disord 1994, 24(5):659-685.
60. Dawson G., Burner K. Behavioral interventions in children and adolescents with autism spectrum disorder: a review of recent findings. Curr Opin Pediatr 2011, 23(6):616-620.
61. Miller D.T., Adam M.P., Aradhya S., et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010, 86(5):749-764.
62. McGrew S.G., Peters B.R., Crittendon J.A., et al. Diagnostic yield of chromosomal microarray analysis in an autism primary care practice: which guidelines to implement?. JAutism Dev Disord 2012, 42(8):1582-1591.
63. Shen Y., Dies K.A., Holm I.A., et al. Clinical genetic testing for patients with autism spectrum disorders. Pediatrics 2010, 125(4):e727-e735.
64. GeneTests Medical Genetics Information Resource (database online). 2012. Available at: Accessed December 18, 2012. http://www.genetests.org.
65. Firth H.V., Richards S.M., Bevan A.P., et al. DECIPHER: database of chromosomal imbalance and phenotype in humans using ensembl resources. Am J Hum Genet 2009, 84(4):524-533.
66. de Ligt J., Willemsen M.H., van Bon B.W., et al. Diagnostic exome sequencing in persons with severe intellectual disability. NEngl J Med 2012, 367(20):1921-1929.
67. Geschwind D.H., Levitt P. Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol 2007, 17(1):103-111.
68. Mefford H.C., Sharp A.J., Baker C., et al. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. NEngl J Med 2008, 359(16):1685-1699.
69. Fernandez T., Morgan T., Davis N., et al. Disruption of contactin 4 (CNTN4) results in developmental delay and other features of 3p deletion syndrome. Am J Hum Genet 2004, 74(6):1286-1293.
70. Glessner J.T., Wang K., Cai G., et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 2009, 459(7246):569-573.
71. Jackman C., Horn N.D., Molleston J.P., et al. Gene associated with seizures, autism, and hepatomegaly in an Amish girl. Pediatr Neurol 2009, 40(4):310-313.
72. Strauss K.A., Puffenberger E.G., Huentelman M.J., et al. Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2. NEngl J Med 2006, 354(13):1370-1377.
73. Varga E.A., Pastore M., Prior T., et al. The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly. Genet Med 2009, 11(2):111-117.
74. Kent L., Bowdin S., Kirby G.A., et al. Beckwith Weidemann syndrome: a behavioral phenotype-genotype study. Am J Med Genet B Neuropsychiatr Genet 2008, 147B(7):1295-1297.
75. Tierney E., Nwokoro N.A., Porter F.D., et al. Behavior phenotype in the RSH/Smith-Lemli-Opitz syndrome. Am J Med Genet 2001, 98(2):191-200.
76. Splawski I., Timothy K.W., Sharpe L.M., et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 2004, 119(1):19-31.
77. Cook E.H., Lindgren V., Leventhal B.L., et al. Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet 1997, 60(4):928-934.
78. Ben-Shachar S., Lanpher B., German J.R., et al. Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. JMed Genet 2009, 46(6):382-388.
79. Bonati M.T., Russo S., Finelli P., et al. Evaluation of autism traits in Angelman syndrome: a resource to unfold autism genes. Neurogenetics 2007, 8(3):169-178.
80. Peters S.U., Beaudet A.L., Madduri N., et al. Autism in Angelman syndrome: implications for autism research. Clin Genet 2004, 66(6):530-536.
81. Descheemaeker M.J., Govers V., Vermeulen P., et al. Pervasive developmental disorders in Prader-Willi syndrome: the Leuven experience in 59 subjects and controls. Am J Med Genet A 2006, 140(11):1136-1142.
82. Kumar R.A., KaraMohamed S., Sudi J., et al. Recurrent 16p11.2 microdeletions in autism. Hum Mol Genet 2008, 17(4):628-638.
83. Weiss L.A., Shen Y., Korn J.M., et al. Association between microdeletion and microduplication at 16p11.2 and autism. NEngl J Med 2008, 358(7):667-675.
84. Potocki L., Bi W., Treadwell-Deering D., et al. Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Am J Hum Genet 2007, 80(4):633-649.
85. Lowenthal R., Paula C.S., Schwartzman J.S., et al. Prevalence of pervasive developmental disorder in Down's syndrome. JAutism Dev Disord 2007, 37(7):1394-1395.
86. Fine S.E., Weissman A., Gerdes M., et al. Autism spectrum disorders and symptoms in children with molecularly confirmed 22q11.2 deletion syndrome. JAutism Dev Disord 2005, 35(4):461-470.
87. Vorstman J.A., Morcus M.E., Duijff S.N., et al. The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. JAm Acad Child Adolesc Psychiatry 2006, 45(9):1104-1113.
88. Manning M.A., Cassidy S.B., Clericuzio C., et al. Terminal 22q deletion syndrome: a newly recognized cause of speech and language disability in the autism spectrum. Pediatrics 2004, 114(2):451-457.
89. Hatton D.D., Sideris J., Skinner M., et al. Autistic behavior in children with fragile X syndrome: prevalence, stability, and the impact of FMRP. Am J Med Genet A 2006, 140A(17):1804-1813.
90. Wetherby A.M., Brosnan-Maddox S., Peace V., et al. Validation of the Infant-Toddler Checklist as a broadband screener for autism spectrum disorders from 9 to 24 months of age. Autism 2008, 12(5):487-511.
91. Robins D.L., Fein D., Barton M.L., et al. The Modified Checklist for Autism in Toddlers: an initial study investigating the early detection of autism and pervasive developmental disorders. JAutism Dev Disord 2001, 31(2):131-144.
92. Allison C., Baron-Cohen S., Wheelwright S., et al. The Q-CHAT (Quantitative CHecklist for Autism in Toddlers): a normally distributed quantitative measure of autistic traits at 18-24 months of age: preliminary report. JAutism Dev Disord 2008, 38(8):1414-1425.
93. Stone W.L., Coonrod E.E., Ousley O.Y. Brief report: screening tool for autism in two-year-olds (STAT): development and preliminary data. JAutism Dev Disord 2000, 30(6):607-612.
94. Berument S.K., Rutter M., Lord C., et al. Autism screening questionnaire: diagnostic validity. Br J Psychiatry 1999, 175:444-451.
95. Constantino J.N., Davis S.A., Todd R.D., et al. Validation of a brief quantitative measure of autistic traits: comparison of the social responsiveness scale with the autism diagnostic interview-revised. JAutism Dev Disord 2003, 33(4):427-433.
96. Reznick J.S., Baranek G.T., Reavis S., et al. Aparent-report instrument for identifying one-year-olds at risk for an eventual diagnosis of autism: the first year inventory. JAutism Dev Disord 2007, 37(9):1691-1710.
97. DeVincent C., Gadow K.D., Strong G., et al. Screening for autism spectrum disorder with the Early Childhood Inventory-4. JDev Behav Pediatr 2008, 29(1):1-10.
98. Gadow K.D., Schwartz J., Devincent C., et al. Clinical utility of autism spectrum disorder scoring algorithms for the child symptom inventory-4. JAutism Dev Disord 2008, 38(3):419-427.
99. Auyeung B., Baron-Cohen S., Wheelwright S., et al. The Autism Spectrum Quotient: Children's Version (AQ-Child). JAutism Dev Disord 2008, 38(7):1230-1240.
100. Rellini E., Tortolani D., Trillo S., et al. Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC) correspondence and conflicts with DSM-IV criteria in diagnosis of autism. JAutism Dev Disord 2004, 34(6):703-708.
101. Lord C., Risi S., Lambrecht L., et al. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. JAutism Dev Disord 2000, 30(3):205-223.
102. Smith T., Groen A.D., Wynn J.W. Randomized trial of intensive early intervention for children with pervasive developmental disorder. Am J Ment Retard 2000, 105(4):269-285.
103. 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(1):e17-e23.
104. Smith I.M., Koegel R.L., Koegel L.K., et al. Effectiveness of a novel community-based early intervention model for children with autistic spectrum disorder. Am J Intellect Dev Disabil 2010, 115(6):504-523.
105. Kaale A., Smith L., Sponheim E. Arandomized controlled trial of preschool-based joint attention intervention for children with autism. JChild Psychol Psychiatry 2012, 53(1):97-105.
106. Landa R.J., Holman K.C., O'Neill A.H., et al. Intervention targeting development of socially synchronous engagement in toddlers with autism spectrum disorder: a randomized controlled trial. JChild Psychol Psychiatry 2011, 52(1):13-21.
107. Kasari C., Freeman S., Paparella T. Joint attention and symbolic play in young children with autism: a randomized controlled intervention study. JChild Psychol Psychiatry 2006, 47(6):611-620.
108. McCracken J.T., McGough J., Shah B., et al. Risperidone in children with autism and serious behavioral problems. NEngl J Med 2002, 347(5):314-321.
109. McDougle C.J., Scahill L., Aman M.G., et al. Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology. Am J Psychiatry 2005, 162(6):1142-1148.
110. 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(5):e634-e641.
111. Nagaraj R., Singhi P., Malhi P. Risperidone in children with autism: randomized, placebo-controlled, double-blind study. JChild Neurol 2006, 21(6):450-455.
112. Marcus R.N., Owen R., Kamen L., et al. Aplacebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. JAm Acad Child Adolesc Psychiatry 2009, 48(11):1110-1119.
113. Owen R., Sikich L., Marcus R.N., et al. Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics 2009, 124(6):1533-1540.
114. Research Units on Pediatric Psychopharmacology Autism Network Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Arch Gen Psychiatry 2005, 62(11):1266-1274.
115. McDougle C.J., Naylor S.T., Cohen D.J., et al. Adouble-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder. Arch Gen Psychiatry 1996, 53(11):1001-1008.
116. Hollander E., Soorya L., Chaplin W., et al. Adouble-blind placebo-controlled trial of fluoxetine for repetitive behaviors and global severity in adult autism spectrum disorders. Am J Psychiatry 2012, 169(3):292-299.
117. Bissler J.J., McCormack F.X., Young L.R., et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. NEngl J Med 2008, 358(2):140-151.
118. Franz D.N., Belousova E., Sparagana S., et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 2013, 381(9861):125-132.
119. Berry-Kravis E., Hessl D., Coffey S., et al. Apilot open label, single dose trial of fenobam in adults with fragile X syndrome. JMed Genet 2009, 46(4):266-271.
120. Berry-Kravis E., Sumis A., Hervey C., et al. Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. JDev Behav Pediatr 2008, 29(4):293-302.