Inherited 1q21.1q21.2 duplication and 16p11.2 deletion: a two-hit case with more severe clinical manifestations.

We report paternally inherited duplication of 1q12q21.2 of 5.8 Mb associated with maternally inherited deletion of 16p11.2 of 545 Kb, this latter first identified in a fetus exhibiting an absent nasal bone detected during pregnancy. During the neonatal period, the young boy presented developmental delay, epilepsy, congenital anomalies and overweight. The clinical features of the proband with two rearrangements were more severe than in either of the parents carrying only one or the other mutation. Thus our data support a two-hit model in which the concomitant presence of these two copy-number variations exacerbates the neurodevelopmental phenotype.