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Diagnostic Yield of Chromosomal Microarray Analysis in an Autism Primary Care Practice: Which Guidelines to Implement?

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Abstract

Genetic testing is recommended for patients with ASD; however specific recommendations vary by specialty. American Academy of Pediatrics and American Academy of Neurology guidelines recommend G-banded karyotype and Fragile X DNA. The American College of Medical Genetics recommends Chromosomal Microarray Analysis (CMA). We determined the yield of CMA (N = 85), karyotype (N = 119), and fragile X (N = 174) testing in a primary pediatrics autism practice. We found twenty (24%) patients with abnormal CMA results (eight were clinically significant), three abnormal karyotypes and one Fragile X syndrome. There was no relationship between CMA result and cognitive level, seizures, dysmorphology, congenital malformations or behavior. We conclude that CMA should be the clinical standard in all specialties for first tier genetic testing in ASD.

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References

  • Achenbach, T. M., & Rescorla, L. A. (2001a). Manual for the ASEBA pre-school forms and profiles. Burlington: University of Vermont, Research Center for Children, Youth, and Families.

    Google Scholar 

  • Achenbach, T. M., & Rescorla, L. A. (2001b). Manual for the ASEBA school-age forms and profiles. Burlington: University of Vermont, Research Center for Children, Youth, and Families.

    Google Scholar 

  • American Academy of Neurology (2000). Practice guidelines: Screening and diagnosis of autism. http://www.aan.com/practice/guideline/index.cfm?fuseaction=home.welcome&keywords=autism+Submit=Search+guidelines. Accessed 7/21/2011.

  • American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders (4th ed, text revision). Washington DC: American Psychiatric Association, (pp. 69–84).

  • Barrett, S., Landa, R., Beck, J. C., & Braun, T. A. (1999). An autosomal genomic screen for autism. American Journal of Medical Genetics, 88, 609–615.

    Google Scholar 

  • Bayley, N. (1993). Bayley scales of infant development (2nd ed.). San Antonio: Psychological Corporation.

    Google Scholar 

  • Berg, J. S., Brunetti-Pierri, N., Peters, S. U., Kang, S. H., et al. (2007). Speech delay and autism spectrum behaviors are frequently associated with duplication of the 7q11.23 Williams-Beuren syndrome region. Genetic Medicine, 9(7), 427–441.

    Article  Google Scholar 

  • Bisgaard, A. M., Kirchhoff, M., Nielsen, J. E., & Brandt, C. (2007). Transmitted cytogenetic abnormalities in patients with mental retardation: pathogenic or normal variants? European Journal of Medical Genetics, 50(4), 243–255.

    Article  PubMed  Google Scholar 

  • Boone, P. M., Bacino, C. A., Shaw, C. A., Eng, P. A., et al. (2010). Detection of clinically relevant exonic copy-number changes by array CGH. Human Mutation, 31(12), 1326–1342.

    Article  PubMed  Google Scholar 

  • Boyle, L., & Kaufmann, W. E. (2010). The behavioral phenotype of FMR1 mutations. American Journal of Medical Genetics Part C: Seminar in Medical Genetics, 154C, 469–476.

    Article  Google Scholar 

  • Brenk, C. H., Prott, E. C., Trost, D., Hoischen, A., et al. (2007). Towards mapping phenotypical traits in 18p-syndrome by array-based comparative genomic hybridisation and fluorescent in situ hybridisation. European Journal of Human Genetics, 15(1), 35–44.

    Article  PubMed  Google Scholar 

  • Burnside, R. D., Pasion, R., Mikhail, F. M., Carroll, A. J., et al. (2011). Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay. Human Genetics [epub ahead of print].

  • Christian, S. L., Brune, C. W., Sudi, J., Kumar, R. A., et al. (2008). Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. Biological Psychiatry, 63(12), 1111–1117.

    Article  PubMed  Google Scholar 

  • Cook, E. H., Jr., Lindgren, V., Leventhal, B. L., Courchesne, R., et al. (1997). Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. American Journal of Human Genetics, 60(4), 928–934.

    PubMed  Google Scholar 

  • Cook, E. H., & Schanen, C. (2008). IDEAS physician advisory. http://www.idic15.org Accessed 5/2011.

  • Courtens, W., Vermeulen, S., Wuyts, W., Messiaen, L., et al. (2005). An interstitial deletion of chromosome 7 at band q21: A case report and review. American Journal of Medical Genetics, 134A(1), 12–23.

    Article  PubMed  Google Scholar 

  • Dauwerse, J. G., Ruivenkamp, C. A., Hansson, K., Marijnissen, G. M., et al. (2010). A complex chromosome 7q rearrangement identified in a patient with mental retardation, anxiety disorder, and autistic features. American Journal of Medical Genetics, 152A(2), 427–433.

    Article  PubMed  Google Scholar 

  • de Ravel, T. J., Thiry, P., & Fryns, J. P. (2005). Follow-up of adult males with chromosome 18p deletion. European Journal of Medical Genetics, 48(2), 189–193.

    Article  PubMed  Google Scholar 

  • DiGuiseppi, C., Hepburn, S., Davis, J., Fidler, D. J., et al. (2010). Screening for autism spectrum disorders in children with Down syndrome: Population prevalence and screening test characteristics. Journal of Developmental and Behavioral Pediatrics, 31(3), 181–191.

    Article  PubMed  Google Scholar 

  • Ezugha, H., Anderson, C. E., Marks, H. G., Khurana, D., et al. (2010). Microarray analysis in children with developmental disorder or epilepsy. Pediatric Neurology, 43(6), 391–394.

    Article  PubMed  Google Scholar 

  • Gilliam, J. E. (2006). Gilliam autism rating scale (2nd ed.). Austin, TX: ProEd.

    Google Scholar 

  • Gonzales, M. L., & LaSalle, J. M. (2010). The role of MeCP2 in brain development and neurodevelopmental disorders. Current Psychiatry Reports, 12(2), 127–134.

    Article  PubMed  Google Scholar 

  • Honda, S., Hayashi, S., Imoto, I., Toyama, J., et al. (2010). Copy-number variations on the X chromosome in Japanese patients with mental retardation detected by array-based comparative genomic hybridization analysis. Journal of Human Genetics, 55(9), 590–599.

    Article  PubMed  Google Scholar 

  • IMGSAC. (1998). A full genome screen for autism with evidence for linkage to a region on chromosome 7q. Human Molecular Genetics, 7(3), 571–578.

    Article  Google Scholar 

  • Jacquemont, M. L., Sanlaville, D., Redon, R., Raoul, O., et al. (2006). Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders. Journal of Medical Genetics, 43(11), 843–849.

    Article  PubMed  Google Scholar 

  • Johnson, C. P., & Myers, S. M. (2007). Identification and evaluation of children with autism spectrum disorders. Pediatrics, 120, 1183–1215.

    Article  PubMed  Google Scholar 

  • Konopka, W., Kiryk, A., Novak, M., Herwerth, M., et al. (2010). MicroRNA loss enhances learning and memory in mice. Journal of Neuroscience, 30(44), 14835–14842.

    Article  PubMed  Google Scholar 

  • Krug, D. A., Arick, J., & Almond, P. (1980). Behavior checklist for identifying severely handicapped individuals with high levels of autistic behavior. Journal of Child Psychology and Psychiatry, 21(3), 221–229.

    Article  PubMed  Google Scholar 

  • Kumar, R. A., KaraMohamed, S., Sudi, J., Conrad, D. F., et al. (2008). Recurrent 16p11.2 microdeletions in autism. Human Molecular Genetics, 17(4), 628–638.

    Article  PubMed  Google Scholar 

  • Liehr, T., Stumm, M., Wegner, R. D., Bhatt, S., et al. (2009). 10p11.2 to 10q11.2 is a yet unreported region leading to unbalanced chromosomal abnormalities without phenotypic consequences. Cytogenet Genome Research, 124(1), 102–105.

    Article  Google Scholar 

  • Lintas, C., & Persico, A. M. (2009). Autistic phenotypes and genetic testing: State-of-the art for the clinical geneticist. Journal of Medical Genetics, 46(1), 1–8.

    Article  PubMed  Google Scholar 

  • Liu, P., Erez, A., Nagamani, S. C., Bi, W., et al. (2011). Copy number gain at Xp22.31 includes complex duplication rearrangements and recurrent triplications. Human Molecular Genetics, 20(10), 1975–1988.

    Article  PubMed  Google Scholar 

  • Lord, C., Risi, S., Lambrecht, L., Cook, E. H., et al. (2000). The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders, 30, 205–223.

    Article  PubMed  Google Scholar 

  • Manguoğlu, E., Berker-Karaüzüm, S., Baumer, A., Mihçi, E., et al. (2005). A case with de novo interstitial deletion of chromosome 7q21.1–q22. Genetic Counseling, 16(2), 155–159.

    PubMed  Google Scholar 

  • Manning, M., & Hudgins, L. (2010). Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genetic Medicine, 12(11), 742–745.

    Article  Google Scholar 

  • McGrew, S., Malow, B. A., Henderson, L., Wang, L., et al. (2007). Developmental and behavioral questionnaire for autism spectrum disorders. Pediatric Neurology, 37(2), 108–116.

    Article  PubMed  Google Scholar 

  • Miles, J. H., & Hillman, R. E. (2000). Value of a clinical morphology examination in autism. American Journal of Medical Genetics, 91, 245–253.

    Article  PubMed  Google Scholar 

  • Miles, J. H., Takahashi, T. N., Bagby, S., Sahota, P. K., et al. (2005). Essential versus complex autism: Definition of fundamental prognostic subtypes. American Journal of Medical Genetics A, 135A, 171–180.

    Article  Google Scholar 

  • Miles, J. H., Takahasi, N., Hong, J., Munden, N., et al. (2008). Development and validation of a measure of dysmorphology: useful for autism subgroup classification. American Journal of Medical Genetics A, 146A(9), 1101–1116.

    Article  Google Scholar 

  • Miller, D. T. (2010). Genetic testing for autism: Recent advances and clinical implications. Expert Review of Molecular Diagnostics, 10, 837–840.

    Article  PubMed  Google Scholar 

  • Miller, D. T., Adam, M. P., Aradhya, S., Biesecker, L. G., et al. (2010). Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. American Journal of Human Genetics, 86(5), 749–764.

    Article  PubMed  Google Scholar 

  • Miller, D. T., Shen, Y., Weiss, L. A., Korn, J., et al. (2009). Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. Journal of Medical Genetics, 46(4), 242–248.

    Article  PubMed  Google Scholar 

  • Muhle, R., Trentacoste, S. V., & Rapin, I. (2004). The genetics of autism. Pediatrics, 113, e472–e486.

    Article  PubMed  Google Scholar 

  • Mullen, E. M. (1995). Mullen scales of early learning (AGS ed.). Circle Pines: American Guidance Service Inc.

    Google Scholar 

  • Numis, A. L., Major, P., Montenegro, M. A., Muzykewicz, D. A., et al. (2011). Identification of risk factors for autism spectrum disorders in tuberous sclerosis complex. Neurology, 76(11), 981–987.

    Article  PubMed  Google Scholar 

  • Ou, Z., Kang, S. H., Shaw, C. A., Carmack, C. E., White, L. D., Patel, A., et al. (2008). Bacterial artificial chromosome-emulation oligonucleotide arrays for targeted clinicalarray-comparative genomic hybridization analyses. Genetic Medicine, 10(4), 278–289.

    Article  Google Scholar 

  • Petti, M., Samanich, J., Pan, Q., Huang, C. K., et al. (2011). Molecular characterization of an interstitial deletion of 1p31.3 in a patient with obesity and psychiatric illness and a review of the literature. American Journal of Medical Genetics, 155(4), 825–832.

    Article  Google Scholar 

  • Phelan, M. C. (2008). Deletion 22q13.3 syndrome. Orphanet Journal of Rare Diseases, 3, 14. doi:10.1186/1750-1172-3-14.

  • Piton, A., Michaud, J. L., Peng, H., Aradhya, S., et al. (2008). Mutations in the calcium-related gene IL1RAPL1 are associated with autism. Human Molecular Genetics, 17(24), 3965–3974.

    Article  PubMed  Google Scholar 

  • Reddy, K. S. (2005). Cytogenetic abnormalities and fragile-X syndrome in autism spectrum disorder. BMC Medical Genetics, 6, 3.

    Article  PubMed  Google Scholar 

  • Roid, G. H. (2003). The Stanford-Binet intelligence scale (5th ed.). Itasca: Riverside Publishing.

    Google Scholar 

  • Ronald, A., & Hoekstra, R. A. (2011). Autism spectrum disorders and autistic traits: A decade of new twin studies. American Journal of Medical Genetics, 156(Part B), 255–274.

    Google Scholar 

  • Rosser, J. (2011). Diagnostic yield of genetic testing in children diagnosed with autism spectrum disorders at a regional referral center. Clinical Pediatric. doi:10.1177/0009922811406261.

  • Schaefer, G. B., & Mendelsohn, N. J. (2008). The professional practice and guidelines committee. Genetics in Medicine, 10(4), 301–305.

    Article  PubMed  Google Scholar 

  • Schopler, E., Reichler, R. J., DeVellis, R. F., & Daly, K. (1980). Toward objective classification of childhood autism: Childhood autism rating scale (CARS). Journal of Autism and Developmental Disorders, 10(1), 91–103.

    Article  PubMed  Google Scholar 

  • Sharp, A. J., Mefford, H. C., Li, K., Baker, C., et al. (2008). A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nature Genetics, 40(3), 322–328.

    Article  PubMed  Google Scholar 

  • Shen, Y., Dies, K. A., Holm, I. A., Bridgemohan, C., et al. (2010). Autism consortium clinical genetics/DNA diagnostics collaboration. Clinical genetic testing for patients with autism spectrum disorders. Pediatrics, 125(4), e727–e735.

    Google Scholar 

  • Shinawi, M., Liu, P., Kang, S. H., Shen, J., et al. (2010). Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size. Journal of Medical Genetics, 47(5), 332–341.

    Article  PubMed  Google Scholar 

  • Sparrow, S., Balla, D., & Cicchetti, D. V. (1984). The Vineland adaptive behavior scales (Survey Form). Circle Pines, MN: American Guidance Service.

    Google Scholar 

  • Terman, L. M., & Merrill, M. A. (1972). Stanford-binet intelligence scale (1972 norms ed.). Boston: Houghton Mifflin.

    Google Scholar 

  • Thomas, J. A., Johnson, J., Peterson Kraai, T. L., Wilson, R., et al. (2003). Genetic and clinical characterization of patients with an interstitial duplication 15q11–q13, emphasizing behavioral phenotype and response to treatment. American Journal of Medical Genetics, 119A(2), 111–120.

    Article  PubMed  Google Scholar 

  • Thorndike, R., Hagen, E., & Sattler, J. (1986). The Stanford-binet intelligence scale (4th ed.). Chicago: Riverside Publishing.

    Google Scholar 

  • Thorson, L., Bryke, C., Rice, G., Artzer, A., et al. (2010). Clinical and molecular characterization of overlapping interstitial Xp21–p22 duplications in two unrelated individuals. American Journal of Medical Genetics, 152A(4), 904–915.

    Article  PubMed  Google Scholar 

  • Van der Aa, N., Rooms, L., Vandeweyer, G., van den Ende, J., et al. (2009). Fourteen new cases contribute to the characterization of the 7q11.23 microduplication syndrome. European Journal of Medical Genetics, 52(2–3), 94–100.

    PubMed  Google Scholar 

  • von der Lippe, C., Rustad, C., Heimdal, K., & Rødningen, O. K. (2011). 15q11.2 microdeletion—Seven new patients with delayed development and/or behavioural problems. European Journal of Medical Genetics, 54(3), 357–360.

    Article  PubMed  Google Scholar 

  • Wechsler, D. (1989). Wechsler preschool and primary scale of intelligence—Revised. San Antonio: The Psychological Corporation.

    Google Scholar 

  • Wechsler, D. (1991). The Wechsler intelligence scale for children (3rd ed.). San Antonio: The Psychological Corporation.

    Google Scholar 

  • Wechsler, D. (2004). The Wechsler intelligence scale for children- (4th ed.). London: Pearson Assessment.

    Google Scholar 

  • Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., et al. (2008). Association between microdeletion and microduplication at 16p11.2 and autism. New England Journal of Medicine, 358(7), 667–675.

    Article  PubMed  Google Scholar 

  • Wester, U., Bondeson, M. L., Edeby, C., & Annerén, G. (2006). Clinical and molecular characterization of individuals with 18p deletion: a genotype-phenotype correlation. American Journal of Medical Genetics A, 140(11), 1164–1171.

    Article  Google Scholar 

  • Yang, M. S., & Gill, M. (2007). A review of gene linkage, association and expression studies in autism and an assessment of convergent evidence. International Journal of Developmental Neuroscience, 25, 69–85.

    Article  PubMed  Google Scholar 

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Acknowledgments

The author acknowledges Dan Coury, M.D., Medical Director for The Autism Treatment Network, a program of Autism Speaks, for his support in the idea generation for this work. This research received no financial support.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Developmental Medicine, Vanderbilt University Medical Center, 11101 Doctors Office Tower, 2200 Children’s Way, Nashville, TN, 37232-9003, USA

    Susan G. McGrew & Julie A. Crittendon

  2. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, 37232-9003, USA

    Brittany R. Peters

  3. Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA

    Susan G. McGrew, Julie A. Crittendon & Jeremy Veenstra-VanderWeele

  4. Departments of Psychiatry, Pediatrics and Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA

    Jeremy Veenstra-VanderWeele

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  1. Susan G. McGrew
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  4. Jeremy Veenstra-VanderWeele
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Correspondence to Susan G. McGrew.

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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?. J Autism Dev Disord 42, 1582–1591 (2012). https://doi.org/10.1007/s10803-011-1398-3

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