Abstract
BackgroundIn countries where comparative genomic hybridization arrays (aCGH) and next generation sequencing are not widely available due to accessibility and economic constraints, conventional 400–500-band karyotyping is the first-line choice for the etiological diagnosis of patients with congenital malformations and intellectual disability. Conventional karyotype analysis can rule out chromosomal alterations greater than 10 Mb. However, some large structural abnormalities, such as derivative chromosomes, may go undetected when the analysis is performed at less than a 550-band resolution and the size and banding pattern of the interchanged segments are similar. Derivatives frequently originate from inter-chromosomal exchanges and sometimes are inherited from a parent who carries a reciprocal translocation.Case presentationWe present two cases with derivative chromosomes involving a 9.1 Mb 5p deletion/14.8 Mb 10p duplication in the first patient and a 19.9 Mb 5p deletion/ 18.5 Mb 9p duplication in the second patient. These long chromosomal imbalances were ascertained by aCGH but not by conventional cytogenetics. Both patients presented with a deletion of the Cri du chat syndrome region and a duplication of another genomic region. Each patient had a unique clinical picture, and although they presented some features of Cri du chat syndrome, the phenotype did not conclusively point towards this diagnosis, although a chromosomopathy was suspected.ConclusionsThese cases highlight the fundamental role of the clinical suspicion in guiding the approach for the etiological diagnosis of patients. Molecular cytogenetics techniques, such as aCGH, should be considered when the clinician suspects the presence of a chromosomal imbalance in spite of a normal karyotype.
Highlights
ConclusionsThese cases highlight the fundamental role of the clinical suspicion in guiding the approach for the etiological diagnosis of patients
In countries where comparative genomic hybridization arrays and generation sequencing are not widely available due to accessibility and economic constraints, conventional 400–500-band karyotyping is the first-line choice for the etiological diagnosis of patients with congenital malformations and intellectual disability
These cases highlight the fundamental role of the clinical suspicion in guiding the approach for the etiological diagnosis of patients
Summary
The phenotype of the patients with a derivative chromosome are unique, since it combines the clinical features of both the partial deletion and the partial duplication. The typical gestalt is modified by non-classical manifestations resulting from the new genome created by the chromosomal rearrangement, and the clinical diagnosis is not apparent. Patients presented here are clear examples in which large chromosomal rearrangements go unnoticed by experienced cytogeneticists when using conventional cytogenetics. These cases highlight the importance of performing complementary analyses in patients with developmental delay or ID associated with CM using molecular cytogenetics techniques. The clinician’s suspicion of a chromosomal etiology for the patient’s condition, despite a normal conventional karyotype, is fundamental to support the need and demand the funding to perform further molecular cytogenetic testing that could positively impact the patient’s diagnosis, and to provide information regarding the biology of the disease
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