Genomic micro-array and whole exome sequencing

Policy context

Genomic micro-array and whole exome sequencing (WES) tests may identify, or confirm the presence of chromosome abnormalities. Whether results from genetic sequencing can improve diagnosis, treatment decisions and health outcomes in some situations remains uncertain.

Status: Decision completed

Primary criteria ranking

  • Safety = Medium
  • Efficacy = High
  • Cost = High

Assessment timeline

  • Draft key questions published: August 16, 2017
  • Public comment period: August 16 to August 29, 2017
  • Final key questions published: September 14, 2017
  • Draft report published: November 9, 2017
  • Public comment period: November 9 to December 8, 2017
  • Final report published: December 22, 2017
  • HTCC public meeting: January 19, 2018


Chromosomes, the genetic structures of a cell, are constructed of deoxyribose nucleic acid (DNA) and the proteins and other elements that protect, regulate, and package the DNA. Humans normally have 23 pairs of chromosomes, with half inherited from each parent. During cell replication, chromosomes are sometimes lost or gained, or broken and rearranged. Rearrangements vary in size and complexity, and may be balanced, with no loss or gain of genetic material, or unbalanced.

Unbalanced chromosomal rearrangements that are present at conception or that occur during fetal development have profound consequences for the developing fetus, resulting in fetal death, structural defects, genetic diseases, or intellectual impairment.5 Chromosomal abnormalities occur in 43.8 per 10,000 births that survive to 20 weeks gestation or later.6 Trisomies 21, 18, and 13; 45, X, and other sex chromosome abnormalities account for most abnormalities. Excluding these, the prevalence of more rare abnormalities is 7.4 per 10,000 births.6 Small pathological duplications or deletions occur in 1 of 270 pregnancies.7 Studies examining the prevalence of chromosomal abnormalities have focused on the prenatal period,6 the prevalence at birth,8 or the prevalence among individuals with specific structural defects9 or developmental disabilities.10  The number of living children or adults with a chromosomal abnormality is unknown. Although the life expectancy for individuals with a chromosomal abnormality may be significantly shortened by birth defects and other conditions, the life span of affected individuals has increased in recent years.

In 2010, the International Standard Cytogenomic Array (ISCA) Consortium released a consensus statement that chromosomal (also known as genomic) microarray should replace G-banded karyotype as a first-tier test for the diagnosis of individuals with developmental disabilities or congenital anomalies.{Miller} In 2013, the American College of Medical Genetics (ACMG) recommended that chromosomal microarray replace G-band karyotype for the clinical evaluation of autism spectrum disorders.{Schaefer} These statements, combined with the increasing prevalence of autism{Van Naarden Braun, 2015 #15}, could greatly increase orders for genomic microarrays. GA results in increased diagnostic yield of GA compared to karyotype, which underlies the ISCA and ACMG consensus statements.{Miller; Schaefer} However, the circumstances in which these tests are most useful, and their contribution to the medical and educational management of affected children is unclear.