Yield of additional genetic testing after chromosomal microarray for diagnosis of neurodevelopmental disability and congenital anomalies: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

doi:10.1038/s41436-018-0040-6

Review

. 2018 Oct;20(10):1105-1113.

doi: 10.1038/s41436-018-0040-6. Epub 2018 Jun 18.

Yield of additional genetic testing after chromosomal microarray for diagnosis of neurodevelopmental disability and congenital anomalies: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Affiliations

¹ Department of Human Genetics, University of Chicago, Chicago, Illinois, USA. dwaggone@genetics.uchicago.edu.
² Autism & Developmental Medicine Institute, Geisinger Health System, Danville, Pennsylvania, USA.
³ Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁴ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
⁵ Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA.
⁶ Department of Pathology, ARUP Laboratories, University of Utah School of Medicine, Salt Lake City, Utah, USA.
⁷ Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women's Hospital, Broad Institute of MIT and Harvard, Harvard Medical School, Boston, Massachusetts, USA.
⁸ Division of Evolution and Genomics Science, School of Biological Sciences, Manchester Academic Health Science Center, Manchester, UK.
⁹ Department of Medical Genetics, Marshfield Clinic, Marshfield, Wisconsin, USA.
¹⁰ Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
¹¹ Laboratory Corporation of America® Holdings, Burlington, North Carolina, USA.
¹² Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA. david.miller2@childrens.harvard.edu.

PMID: 29915380
PMCID: PMC6410698
DOI: 10.1038/s41436-018-0040-6

Review

Yield of additional genetic testing after chromosomal microarray for diagnosis of neurodevelopmental disability and congenital anomalies: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Darrel Waggoner et al. Genet Med. 2018 Oct.

. 2018 Oct;20(10):1105-1113.

doi: 10.1038/s41436-018-0040-6. Epub 2018 Jun 18.

Affiliations

¹ Department of Human Genetics, University of Chicago, Chicago, Illinois, USA. dwaggone@genetics.uchicago.edu.
² Autism & Developmental Medicine Institute, Geisinger Health System, Danville, Pennsylvania, USA.
³ Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁴ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
⁵ Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA.
⁶ Department of Pathology, ARUP Laboratories, University of Utah School of Medicine, Salt Lake City, Utah, USA.
⁷ Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women's Hospital, Broad Institute of MIT and Harvard, Harvard Medical School, Boston, Massachusetts, USA.
⁸ Division of Evolution and Genomics Science, School of Biological Sciences, Manchester Academic Health Science Center, Manchester, UK.
⁹ Department of Medical Genetics, Marshfield Clinic, Marshfield, Wisconsin, USA.
¹⁰ Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
¹¹ Laboratory Corporation of America® Holdings, Burlington, North Carolina, USA.
¹² Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA. david.miller2@childrens.harvard.edu.

PMID: 29915380
PMCID: PMC6410698
DOI: 10.1038/s41436-018-0040-6

Abstract

Purpose: Chromosomal microarray (CMA) is recommended as the first-tier test in evaluation of individuals with neurodevelopmental disability and congenital anomalies. CMA may not detect balanced cytogenomic abnormalities or uniparental disomy (UPD), and deletion/duplications and regions of homozygosity may require additional testing to clarify the mechanism and inform accurate counseling. We conducted an evidence review to synthesize data regarding the benefit of additional testing after CMA to inform a genetic diagnosis.

Methods: The review was guided by key questions related to the detection of genomic events that may require additional testing. A PubMed search for original research articles, systematic reviews, and meta-analyses was evaluated from articles published between 1 January 1983 and 31 March 2017. Based on the key questions, articles were retrieved and data extracted in parallel with comparison of results and discussion to resolve discrepancies. Variables assessed included study design and outcomes.

Results: A narrative synthesis was created for each question to describe the occurrence of, and clinical significance of, additional diagnostic findings from subsequent testing performed after CMA.

Conclusion: These findings may be used to assist the laboratory and clinician when making recommendations about additional testing after CMA, as it impacts clinical care, counseling, and diagnosis.

Keywords: Balanced rearrangement; Chromosomal microarray; UPD; genetic testing; mosaicism.

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References

1. Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic testing for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010;86(5):749–764. - PMC - PubMed
1. Manning M, Hudgins L. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med 2010;12(11):742–745. - PMC - PubMed
1. Michelson DJ, Shevell MI, Sherr EH, et al. Evidence report: genetic and metabolic testing on children with global developmental delay: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2011;77(17):1629–1635. - PubMed
1. Turner G, Boyle J, Partington MW, et al. Restoring reproductive confidence in families with X-linked mental retardation by finding the causal mutation. Clin Genet 2008;73(2):188–190. - PubMed
1. Saam J, Gudgeon J, Aston E, Brothman AR. How physicians use array comparative genomic hybridization results to guide patient management in children with developmental delay. Genet Med 2008;10(3):181–186. - PubMed

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[1] Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic testing for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010;86(5):749–764. - PMC - PubMed

[2] Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic testing for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010;86(5):749–764. - PMC - PubMed

[3] Manning M, Hudgins L. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med 2010;12(11):742–745. - PMC - PubMed

[4] Manning M, Hudgins L. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med 2010;12(11):742–745. - PMC - PubMed

[5] Michelson DJ, Shevell MI, Sherr EH, et al. Evidence report: genetic and metabolic testing on children with global developmental delay: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2011;77(17):1629–1635. - PubMed

[6] Michelson DJ, Shevell MI, Sherr EH, et al. Evidence report: genetic and metabolic testing on children with global developmental delay: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2011;77(17):1629–1635. - PubMed

[7] Turner G, Boyle J, Partington MW, et al. Restoring reproductive confidence in families with X-linked mental retardation by finding the causal mutation. Clin Genet 2008;73(2):188–190. - PubMed

[8] Turner G, Boyle J, Partington MW, et al. Restoring reproductive confidence in families with X-linked mental retardation by finding the causal mutation. Clin Genet 2008;73(2):188–190. - PubMed

[9] Saam J, Gudgeon J, Aston E, Brothman AR. How physicians use array comparative genomic hybridization results to guide patient management in children with developmental delay. Genet Med 2008;10(3):181–186. - PubMed

[10] Saam J, Gudgeon J, Aston E, Brothman AR. How physicians use array comparative genomic hybridization results to guide patient management in children with developmental delay. Genet Med 2008;10(3):181–186. - PubMed

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Yield of additional genetic testing after chromosomal microarray for diagnosis of neurodevelopmental disability and congenital anomalies: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Affiliations

Yield of additional genetic testing after chromosomal microarray for diagnosis of neurodevelopmental disability and congenital anomalies: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

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