Clinical and molecular cytogenetic characterization of four unrelated patients carrying 2p14 microdeletions

We report the clinical and molecular cytogenetic characterization of four unrelated patients from France and Spain, carrying 2p14 microdeletions and presenting with intellectual disability and dysmorphisms. 2p14 microdeletions are very rare. Seven patients have been reported so far harboring deletions including 2p14p15 and encompassing OTX1, whose haploinsufficiency is frequently associated with genitourinary defects. To date, only one patient has been reported carrying a more proximal 2p14 microdeletion which does not include OTX1. Here, we report three further patients carrying proximal 2p14 microdeletions not including OTX1 and one patient carrying a more distal 2p14p15 microdeletion including this gene, providing new insights into the associated phenotypic spectrum. First, our study and a review of the literature showed that 3/4 patients carrying proximal 2p14 microdeletions had sensorineural hearing loss, suggesting the presence of a previously unreported deafness-causing gene in this chromosomal region. Second, one patient developed a progressive cardiomyopathy, suggesting that a cardiac follow-up should be systematically warranted even in the absence of congenital heart disease. We speculate that ACTR2 and MEIS1 might respectively play a role in the pathogenesis of the observed deafness and cardiomyopathy. Third, we observed other previously unreported features such as glaucoma, retinopathy, and mild midline abnormalities including short corpus callosum, hypospadias and anteriorly placed anus. Finally, the patient carrying a 2p14p15 deletion including OTX1 had normal kidneys and genitalia, thus confirming that OTX1 haploinsufficiency is not invariably associated with genitourinary defects. In conclusion, our study contributes significantly to delineate the phenotypic spectrum of 2p14 microdeletions.