Background Array comparative genomic hybridisation (aCGH) represents a major advance in the ability to detect chromosomal imbalances (CI). A recent meta-analysis recommended aCGH for replacing karyotyping for patients with unexplained disabilities. However, favouring aCGH over karyotyping must be based on solid evidence due to the major implications of selecting a preferential diagnostic tool.

Methods and results A prospective study of 376 samples was conducted to assess the relevance of karyotyping after a first-tier aCGH in patients with unexplained disabilities. aCGH detected CI in 28.7% of the cases. Out of 376 patients, 288 had undergone parallel karyotyping testing: 69.8% (201/288) showed similar results for both aCGH and karyotyping. For patients with a CI detected by aCGH, 7.9% (7/89) showed similar results for both aCGH and karyotyping. Among 20 patients with abnormal karyotyping, 13 showed dissimilar results compared to aCGH analysis: 4 patients (1.4%) had balanced rearrangements and 9 patients (3.1%) had additional chromosomal anomalies unseen using aCGH. This rate of unseen chromosomal anomalies is far superior to the previously estimated 0.5–0.78% prevalence and affects 10.1% (9/89) of patients with CI detected by aCGH in the tested population.

Conclusions Since the clinical significance of CI identified by aCGH might be influenced by such discrepancies between the two methods, these may in turn have an impact on clinical diagnosis and patient counselling. It is proposed that each genetic laboratory should evaluate the relevance of karyotyping for all first-tier abnormal aCGH results in order to include the genomic (chromosomal) aspects of the aCGH findings in the diagnosis.