Nonsyndromic Microcephaly: An Overview

Abstract

Microcephaly is the term customarily used by clinicians to refer to a patient’s head size significantly below the mean for ageand sex-appropriate reference values for occipitofrontal circumference (OFC). It is not a specific diagnosis but merely a clinical sign, a finding on physical examination, which is causally very heterogeneous. Microcephaly is rarely a parental complaint, and it is often unrecognized by the physician, as clinical inspection may be misleading and objective measurements are, unfortunately, commonly omitted. Microcephaly is either the consequence of different developmental anomalies or inborn errors of metabolism that adversely affect the intracranial central nervous system (CNS), or of its disruption by various environmental factors. Irrespective of its cause and pathogenesis, microcephaly results from lack of expansive growth of the brain. The normal prenatal and postnatal increase in size of the human skull is in part a component of normal skeletal growth, but most importantly, a phenomenon dependent on intensive brain growth in infancy and early childhood. Usually, microcephaly is associated with moderate to severe mental retardation (MR) and often with other CNS dysfunctions. Paradoxically, only about one quarter of patients with MR, irrespective of associated CNS dysfunction, have true microcephaly. Because of its complex etiology, micro-