7q35q36.3 deletion and concomitant 20q13.2q13.33 duplication in a newborn: familiar case

Abstract

Objective: Array-CGH is a powerful tool in identifying and characterizing complex genomic rearrangements smaller than 5-10 megabase (Mb), for which classical cytogenetic approaches are not sensitive enough. The use of Array-CGH has increased of 10-20% the detection rate of unbalanced cryptic rearrangements, such as deletions and/or duplications.

Patients and methods: We present here the first report of a patient with 7q35q36.3 microdeletion and concomitant 20q13.2q13.33 microduplication detected by array-CGH and confirmed by reiterative FISH experiments associated with dysmorphism, development delay, Long QT syndrome (LQTS), complex congenital heart disease, pulmonary hypertension, hypotonia, respiratory distress, cognitive deficit.

Results: We proved that this unbalanced rearrangement was due to an adjacent-1 segregation that occurred in the mother, carrier of a balanced translocation between chromosomes 7 and 20. The same unbalanced rearrangements were also found in the proband's maternal uncle, who had been given a clinical diagnosis of Dandy-Walker/Rubinstein-Taybi syndromes in the past. Given the above-mentioned observations, the proband's uncle is not affected by Dandy-Walker/Rubinstein-Taybi syndromes, but by a genomic syndrome highlighted by array-CGH.

Conclusions: The Array-CGH allowed us to understand that the loss of several genes is expressed with clinical manifestations due to the concomitance of several syndromes, each related to the malfunction of a "specific disease gene". For these reasons, the genotype-phenotype correlation in these cases is more complex. This study confirms that the array-CGH is useful in identifying pathologies that were considered idiopathic until a few years ago.