Chapter 8. Abnormalitiesof Head Size: Microcephaly and Macrocephaly

Definitions and Epidemiology

Head size is an easily measured clinical finding that can be followed over time. The head circumference is measured around the forehead and the occipital protuberance. Microcephaly is defined by a head circumference more than two standard deviations below the mean for a given demographic (age, gender, race). Small head size is an indication of the underlying brain size except in cases of craniosynostosis, or premature closure of the bony sutures.

The posterior fontanelle should close by age 3 months and anterior fontanelle by 20 months. Fibrous union of the suture lines occurs by about age 6 months. The craniobasal bones are ossified by age 8 years. The remaining sutures are visible on x-ray until approximately age 20 years but can resist elevated intracranial pressure by age 12 years.1

Pathogenesis

Primary Microcephaly

Primary microcephaly occurs because of genetic or environmental factors that produce small brain size (micrencephaly). The genetic form of primary microcephaly can be inherited by either autosomal dominant or autosomal recessive mechanisms.2 A variety of neuronal migrational disorders—lissencephaly, schizencephaly, agensesis of the corpus callosum, and polymicrogyria—can be associated with microcephaly. Incomplete neurogenesis can also cause microcephaly secondary to insufficient neuronal production. Disorders such as anencephaly can also result in microcephaly (Figure 8-1). While the inheritance for microcephaly has been linked to chromosomes 1, 9, and 19, linkages are likely to be found with genes mapping to a number of other chromosomes.3–5 Chromosomal disorders including Down syndrome and other trisomy disorders can produce microcephaly.

Exposure to ionizing radiation during the first two trimesters can result in microcephaly.6,7 It does not appear that exposure to low levels of radiation associated with diagnostic imaging (x-ray, CT, MRI) pose any significant increased risk for the development of microcephaly.

Prenatal infections do, however, increase the risk for microcephaly. Cytomegalovirus (CMV), rubella virus, and toxoplasmosis are the most well-known causes of microcephaly, but numerous infections in utero can increase this risk.8

Fetal exposure to certain chemicals during neuronal induction or cellular migration also increases the risk of microcephaly.

Secondary Microcephaly

As opposed to disorders interrupting cerebral development associated with primary microcephaly, secondary microcephaly arises following neuronal injury. Prenatal cerebral infarction, meningitis, encephalitis, trauma, hypoxia, and metabolic disorders can result in this neuronal injury.

Craniosynostosis is premature closure of at least one of the cranial bony sutures.9 Primary craniosynostosis is caused by abnormalities of the mesenchymal matrix. Secondary craniosynostosis can occur in association with a number of hematologic, metabolic, and in some cases mechanical disorders.

Craniosynostosis is associated with a number of genetic disorders including Aperts syndrome, Crouzon syndrome, Jackson-Weiss syndrome, ...