Microcephaly a­nd M­eg­alencephaly: Disorders of Brain Size

An understanding of human brain size begins with studies of normal head growth in childhood. The occipitofrontal circumference (OFC) of full-term infants measures 32-37cm at birth and increases by ~0.4cm per week during the first several months, by ~1cm per month during the remainder of the first year, and ~0.2cm per month during the second year of life. With normal growth, OFC reaches ~80% of adult size by 1 year and ~86% by 2 years of age and eventually reaches the adult human OFC of 52-57.5cm for females and 54-59.7cm for males. Evaluating head size in children represents a conundrum. Normal head growth is traditionally defined as 2 standard deviations (SD) above or below the mean for age and sex. Head size follows a normal distribution so that ~2.3% of individuals have a head size above +2SD and another ~2.3% head size below -2SD, groups that include many developmentally normal individuals. Not surprisingly, ~1% of referrals to Pediatric Neurology request evaluation of microcephaly (MIC). Thus disorders of brain size—MIC (small head and brain), macrocephaly (MAC, large head), and megalencephaly (MEG; large brain)—need to be reconsidered. Most experts including the author define clinically significant MIC and MAC-MEG as OFC of 3SD or more below or above the mean. Individuals with OFC of 2 to less than 3SD above or below the mean are then designated as mild or borderline MIC (bMIC) or MAC-MEG, an important distinction as many individuals in these groups have normal intelligence quotient (IQ). When no birth data are available, OFC of 4SD or more below the mean should be used for congenital MIC. Even using this stricter definition, MIC and MEG are common. Given a normal distribution, ~0.1% of individuals have a head size more than 3SD above or below the mean. This implies that at least ~96,000 of the 71.8 million children living in the United States as of 2020 have MIC. The same argument applies for MAC-MEG, but this criterion includes any cause of a large head size, including hydrocephalus and other causes addressed elsewhere in the book.