Megalencephaly, hydrocephalus and cortical dysplasia in severe dwarfism mimicking leprechaunism

Abstract

This report concerns an autopsy case of megalencephaly exhibiting a unique combination of physical and brain malformations. A 4-year-old boy had a peculiar face, a severe reduction of subcutaneous adipose tissue, severe growth failure and frequent hypoglycemic episodes. These clinical features were compatible with leprechaunism; however, the absence of hyperinsulinemia and insulin resistance prevented the diagnosis of leprechaunism. The autopsy disclosed complex cardiac and brain malformations. Although hydrocephalus coexisted, the brain weight after complete removal of the cerebrospinal fluid was 2260 g, which was greater than the average brain weight of normal Japanese children of the same age. The neuronal density in the cerebral cortex was decreased, while the surface area of the cerebral cortex and white matter were greater than those in an age-matched control. There was cortical dysplasia in the frontal and parietal lobes. Endocrine tests and immunohistochemical analysis of the brain did not demonstrate any abnormalities in the hypothalamus-pituitary system. Megalencephaly can be associated with dwarfism, and this case is important for consideration of the interrelationship between neuronal proliferation and physical growth.