Ann Lab Med.  2019 May;39(3):299-310. 10.3343/alm.2019.39.3.299.

Chromosomal Microarray Analysis as a First-Tier Clinical Diagnostic Test in Patients With Developmental Delay/Intellectual Disability, Autism Spectrum Disorders, and Multiple Congenital Anomalies: A Prospective Multicenter Study in Korea

Affiliations
  • 1Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. microkim@catholic.ac.kr
  • 2Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 3Department of Rehabilitation Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea.
  • 4Department of Rehabilitation Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea.
  • 5Department of Rehabilitation Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea.
  • 6Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 7Department of Pediatrics, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea.
  • 8Department of Pediatrics, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 9Department of Laboratory Medicine, Inha University School of Medicine, Incheon, Korea.
  • 10Department of Rehabilitation Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Abstract

BACKGROUND
To validate the clinical application of chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic test and to determine the impact of CMA results on patient clinical management, we conducted a multicenter prospective study in Korean patients diagnosed as having developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA).
METHODS
We performed both CMA and G-banding cytogenetics as the first-tier tests in 617 patients. To determine whether the CMA results directly influenced treatment recommendations, the referring clinicians were asked to complete a 39-item questionnaire for each patient separately after receiving the CMA results.
RESULTS
A total of 122 patients (19.8%) had abnormal CMA results, with either pathogenic variants (N=65) or variants of possible significance (VPS, N=57). Thirty-five well-known diseases were detected: 16p11.2 microdeletion syndrome was the most common, followed by Prader-Willi syndrome, 15q11-q13 duplication, Down syndrome, and Duchenne muscular dystrophy. Variants of unknown significance (VUS) were discovered in 51 patients (8.3%). VUS of genes putatively associated with developmental disorders were found in five patients: IMMP2L deletion, PTCH1 duplication, and ATRNL1 deletion. CMA results influenced clinical management, such as imaging studies, specialist referral, and laboratory testing in 71.4% of patients overall, and in 86.0%, 83.3%, 75.0%, and 67.3% of patients with VPS, pathogenic variants, VUS, and benign variants, respectively.
CONCLUSIONS
Clinical application of CMA as a first-tier test improves diagnostic yields and the quality of clinical management in patients with DD/ID, ASD, and MCA.

Keyword

Chromosomal microarray analysis; Pathogenic; Variant of possible significance; Variant of unknown significance; Benign; Clinical management; Developmental delay; Intellectual disability; Autism spectrum disorders; Multiple congenital anomalies

MeSH Terms

Autism Spectrum Disorder*
Autistic Disorder*
Cytogenetics
Diagnostic Tests, Routine*
Down Syndrome
Humans
Intellectual Disability
Korea*
Microarray Analysis*
Muscular Dystrophy, Duchenne
Prader-Willi Syndrome
Prospective Studies*
Referral and Consultation
Specialization
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