Sengers syndrome is characterized by a constellation of congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, and lactic acidosis. Two forms of the disease have been described: a fatal neonatal form, and a more benign form in which patients live into their second or third decades. With the exception of time to death, no findings have distinguished these two forms. We present 3 cases of neonatal Sengers syndrome with significant central nervous system involvement, a finding not previously described. We suggest that the fatal neonatal form of Sengers syndrome would be more accurately described as a mitochondrial encephalomyopathy. Cranial imaging may help distinguish the two types of this syndrome.