Prenatal disruptive injuries within one or both cerebellar hemispheres, which are mostly caused by hemorrhages, are well known. Primary disruptive lesions of the brainstem, however, are exceptional. Here we report on clinical and neuroimaging findings, as well as outcome of four male infants with prenatal brainstem disruptions that have been seen between 2005 and 2015. Two infants with extensive brainstem defects (from the midbrain to the medulla) had respiratory insufficiency and died at the age of 12 weeks and 22 months, respectively. Two patients had smaller, unilateral/asymmetrical lesions in the pontomesencephalic and medullary regions, respectively, and presented with permanent multiple cranial nerve deficits and long-tract signs. Recognition of prenatal brainstem disruptions and distinction from malformations are essential for the management and the estimation of a recurrence risk.