Society Statements on Whole-Genome Sequencing for Rare Disease
The promise of WGS to improve diagnosis and management of rare disease is being validated in clinical practice and recognized by societies. In 2021, the American College of Medical Genetics and Genomics (ACMG) released guidance recommending the use of whole-exome sequencing or whole-genome sequencing as first- or second-tier tests in patients with one or more congenital anomalies prior to one year of age or intellectual disabilities/developmental delay prior to eighteen years of age. Medical societies across the world also recommend whole-genome sequencing as a first or second-tier diagnostic test for rare disease.
ACMG – American College of Medical Genetics and Genomics
Patients with one or more congenital anomalies prior to one year of age OR with intellectual disability with onset prior to age 18.
NSGC – National Society of Genetic Counselors
Genetic testing is strongly recommended for all individuals with unexplained epilepsy, without limitation of age, with exome/genome sequencing and/or a multi-gene panel (>25 genes) as first-tier testing followed by chromosomal microarray, with exome/genome sequencing conditionally recommended over multi-gene panel.
ESHG – European Society of Human Genetics
It is recommended to introduce WGS analysis in a diagnostic setting when it is a relevant improvement on quality, efficiency and/or diagnostic yield.
RACP – Royal Australasian College of Physicians, Paediatric and Child Health Division
Any child < 10 years with: facial dysmorphism AND ≥ 1 congenital structural anomaly; OR global developmental delay/ intellectual disability (moderate to severe); Test must be requested by clinical geneticist OR pediatrician following consultation with clinical Geneticist.
CMDA – Chinese Medical Doctor Association, Medical Genetics Branch
Non-specific phenotype associated with intellectual disability and/or developmental delay; multiple congenital anomalies.
Clear clinical diagnosis associated with high level of genetic heterogeneity. Previously negative WES or CMA.
National Projects Evaluating the Clinical and Cost-Effectiveness of WGS in Practice
The following special projects were designed to evaluate the clinical and economic impacts of rapid WGS for critically ill children. These pioneering initiatives are generating evidence of clinical utility and economic benefits that will make it easier for other institutions to follow.
Project Baby Deer
Five hospitals across Michigan offering rapid WGS to newborns and children up to 18 years.
Focus: Decreased hospital stays for NICU patients, which led Michigan to be the first state to mandate Medicare coverage of rapid WGS.
Clinical utility research is ongoing