22q11.2 Microduplication in Two Patients with Bladder Exstrophy and Hearing Impairment

Abstract

Purpose Bladder exstrophy is a congenital malformation of the bladder occurring in about 1 in 35 000 newborns. A few cases of bladder exstrophy patients have been described to carry chromosomal aberrations and in addition the recurrence risk in higher among relatives of bladder exstrophy cases than in the general population. This speaks in favour of a genetic contribution to the pathogenesis of bladder exstrophy. Material and Methods We have performed array-CGH analysis of 36 Swedish bladder exstrophy patients in order to look for submicroscopic chromosomal aberrations. Results The analysis revealed a 22q11.21 microduplication in two unrelated cases with bladder exstrophy and hearing impairment consistent with the recently described 22q11.2 microduplication syndrome. This finding was confirmed by multiplex ligation-dependent probe amplification (MLPA) and FISH analysis. Subsequent MLPA analysis of this chromosomal region in 33 bladder exstrophy patients did not reveal any deletion/duplication within this region. MLPA analysis of 171 anonymous control individuals revealed one individual carrying this microduplication. Conclusions Chromosomal rearrangements of 22q11.2 are implicated in several genomic disorders i.e. DiGeorge/velocardiofacial- and cat-eye syndrome. Deletions within this chromosomal region are relatively common while duplications of 22q11.2 are much less frequently observed. An increasing number of reports of microduplications of this region describe a highly variable phenotype. This is the first report of 22q11.2 microduplication associated with bladder exstrophy and hearing impairment. The finding of one carrier among a cohort of normal controls further highlights the variable phenotype linked to this microduplication syndrome.