Chromosomal microarray analysis as a first-tier clinical diagnostic test: Estonian experience.

Area of Science:

• Genetics
• Medical Diagnostics

Background:

• Chromosomal microarray analysis (CMA) is the primary cytogenetic test for developmental delay/intellectual disability (DD/ID), multiple congenital anomalies (MCA), and autism spectrum disorders (ASD).
• CMA has been integrated into routine diagnostics in Estonia since 2011, supported by the Estonian Health Insurance Fund.

Purpose of the Study:

• To report the experience and findings of CMA implementation for postnatal and prenatal diagnoses in Estonian patients between 2009 and 2012.
• To evaluate the diagnostic yield and challenges associated with CMA interpretation in a clinical setting.

Main Methods:

• Analysis of 1191 patients (1072 postnatal, 60 prenatal) and 59 family members using CMA.
• Categorization of detected chromosomal abnormalities, including deletions, duplications, long contiguous stretches of homozygosity (LCSH), and aneuploidies.
• Classification of findings based on clinical significance: pathogenic, likely pathogenic, unknown, and benign/likely benign.

Main Results:

• Abnormal results were identified in 25% of patients, with 351 total findings (deletions, duplications, LCSH, aneuploidies).
• Clinically relevant findings were detected in 11% of patients.
• A significant proportion (41%) of findings were variants of unknown clinical significance, predominantly LCSH events.

Conclusions:

• CMA is a powerful tool for detecting chromosomal abnormalities in patients with DD/ID, MCA, and ASD.
• The high rate of variants of unknown clinical significance highlights the need for improved interpretation strategies and further research.
• Close collaboration between clinicians and cytogeneticists is crucial for accurate CMA interpretation and patient management.