# Chromosomal microarray testing yield in 829 cases of microcephaly: a clinical characteristics-based analysis for prenatal and postnatal cases

## TL;DR

This study shows that chromosomal microarray testing finds genetic abnormalities in 4.6% of prenatal and 15% of postnatal microcephaly cases, with higher detection rates when other symptoms are present.

## Contribution

The study provides a clinical characteristics-based analysis of CMA testing yield in microcephaly cases, comparing prenatal and postnatal outcomes.

## Key findings

- Prenatal microcephaly cases had a 4.6% CMA yield, higher than low-risk pregnancies.
- Postnatal cases had a 15.0% CMA yield, with higher detection when combined with dysmorphism, hypotonia, and other symptoms.
- No specific recurrent CNVs were found, and 3.9% of results were variants of unknown significance.

## Abstract

Microcephaly, characterized by abnormal head growth, can often serve as an initial indicator of congenital, genetic, or acquired disorders. In this study, we sought to evaluate the effectiveness of chromosomal microarray (CMA) testing in detecting abnormalities in both prenatal and postnatal cases of microcephaly.

CMA Testing: We conducted CMA testing on 87 prenatally-detected microcephaly cases and 742 postnatal cases at a single laboratory. We evaluated the CMA yield in relation to specific clinical characteristics.

In prenatal cases, pathogenic and likely pathogenic (LP) results were identified in 4.6% of cases, a significantly higher rate compared to low-risk pregnancies. The male-to-female ratio in this cohort was 3, and the CMA yield was not influenced by gender or other clinical parameters. For postnatal cases, the CMA yield was 15.0%, with a significantly higher detection rate associated with dysmorphism, hypotonia, epilepsy, congenital heart malformations (CHM), learning disabilities (LD), and a history of Fetal growth restriction (FGR). No specific recurrent copy number variations (CNVs) were observed, and the rate of variants of unknown significance was 3.9%.

The yield of CMA testing in prenatal microcephaly is lower than in postnatal cases (4.6% vs. 15%). The presence of microcephaly, combined with dysmorphism, hypotonia, epilepsy, CHD, LD, and FGR, significantly increases the likelihood of an abnormal CMA result.

The online version contains supplementary material available at 10.1007/s00404-024-07388-3.