Genetic Counseling and Genome Sequencing in Pediatric Rare Disease

Cold Spring Harb Perspect Med. 2020 Mar 2;10(3):a036632. doi: 10.1101/cshperspect.a036632.


Both genome sequencing (GS) and exome sequencing (ES) have proven to be revolutionary in the diagnosis of pediatric rare disease. The diagnostic potential and increasing affordability make GS and ES more accessible as a routine clinical test in some centers. Herein, I review aspects of rare disease in pediatrics associated with the use of genomic technologies with an emphasis on the benefits and limitations of both ES and GS, complexities of variant classification, and the importance of genetic counseling. Indications for testing, the role of genetic counselors in genomic test selection, and the diagnostic potential of ES and GS in various pediatric multisystem disorders are discussed. The neonatal population represents an important cohort in pediatric rare disease. Rapid ES and GS in critically ill neonates can have an immediate impact on medical management and present unique genetic counseling challenges. This work includes reviews of recommendations for genetic counseling for families considering genome-wide sequencing, and issues of access to genetic counseling that affect clinical use and will necessitate implementation of innovative methods such as online decision aids. Finally, this work will also review the challenges of having a child with a rare disease, the impact of results from ES and GS on these families, and the role of various support agencies.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Databases, Genetic
  • Genetic Counseling*
  • Genetic Diseases, Inborn / diagnosis*
  • Genetic Testing*
  • Humans
  • Infant
  • Infant, Newborn
  • Intensive Care Units, Neonatal
  • Pediatrics
  • Practice Guidelines as Topic
  • Rare Diseases / genetics*
  • Whole Exome Sequencing*