Clinical application of CNV-seq for diagnosing abnormal brain development in children

Area of Science:

• Medical Genetics
• Pediatric Neurology
• Genomic Medicine

Background:

• Abnormal brain development (ABD) presents a significant diagnostic challenge in pediatric patients.
• Identifying the genetic etiology is crucial for accurate diagnosis, prognosis, and management.
• Copy number variation sequencing (CNV-Seq) is an emerging tool for detecting genetic abnormalities.

Purpose of the Study:

• To evaluate the diagnostic utility of CNV-Seq in pediatric patients with ABD.
• To compare the detection rates of genetic abnormalities between syndromic (S-ABD) and non-syndromic (NS-ABD) groups.
• To assess the clinical implications of CNV-Seq findings for patient management.

Main Methods:

• Retrospective analysis of 130 pediatric patients diagnosed with ABD.
• Categorization into syndromic (S-ABD) and non-syndromic (NS-ABD) groups.
• Application of CNV-Seq to identify chromosomal aneuploidies and copy number variations (CNVs).

Main Results:

• Overall, 32.3% of patients had detectable genetic abnormalities, including aneuploidies and CNVs.
• Pathogenic CNV (pCNV) detection was significantly higher in the S-ABD group (70.4%) compared to the NS-ABD group (26.7%).
• Non-syndromic ABD cases showed a higher proportion of variants of uncertain significance (VUS) and a lower positive detection rate, posing a risk of underdiagnosis.

Conclusions:

• CNV-Seq is a valuable diagnostic tool for pediatric ABD, with a high yield in syndromic cases.
• The lower detection rate in NS-ABD patients underscores the need for careful clinical evaluation and potentially advanced genetic testing.
• Improved genetic counseling and timely prenatal diagnosis are essential for better clinical outcomes in ABD patients.