Macrocephaly is defined as a head circumference greater than 3 SD above the mean for age and sex. The terms macroencephaly and megaloencephaly have been used interchangeably with macrocephaly, which indicates an increased brain volume in the absence of hydrocephalus (Gooskens et al., 1988). It may be associated with subdural hematoma, other space-occupying lesions, an unduly thickened skull, or a large brain (Lorber and Priestley, 1981). Normal brains of adults usually weigh less than 1500 g. Weights above this are considered abnormal and macrocephalic. At birth the normal brain weighs approximately 370 g. Almost all cases of macrocephaly represent normal variants with a normal large brain (Lorber and Priestley, 1981).

The most common variety of this condition is benign familial macrocephaly, accounting for at least 50% of cases. It is usually associated with an autosomal dominant pattern of inheritance (DeMeyer, 1972). There is a male to female preponderance of 4:1 (Lorber and Priestley, 1981). Isolated sporadic macrocephaly without evidence of a familial disorder is less common (DeMeyer, 1972; Pettit et al., 1980). Macrocephaly may also be associated with generalized disorders of overgrowth, such as cerebral gigantism (Sotos syndrome), Beckwith–Wiedemann syndrome, Weaver syndrome, and achondroplasia (Ott and Robinson, 1969; Dodge et al., 1983) (see Chapter 124) (Figure 18-1).

Several neurocutaneous disorders are associated with macrocephaly. It is seen most consistently with multiple hemangiomatosis syndrome (Riley and Smith, 1960) and Bannayan–Riley–Ruvalcaba syndrome (Gorlin et al., 1992). Hypotonia associated with gross motor and developmental delay is also common (DiLiberti, 1992). In one series of 14 children with hypotonia and macrocephaly, 13 demonstrated evidence of lipid storage myopathy on muscle biopsy (DiLiberti, 1992). All 13 children had clinical examinations consistent with either benign familial macrocephaly or the Bannayan–Riley–Ruvalcaba syndrome. Although macrocephaly is generally a benign condition, in several series it has been associated with intellectual impairment. A syndrome of X-linked mental retardation associated with macrocephaly, coarse facies, hypertelorism, and macro-orchidism has been reported (Atkin et al., 1985). The affected males were moderately intellectually impaired, and there was some expression in heterozygotes. In another report, three sisters with moderate to severe intellectual impairment together with macrocephaly and distinctive facies were described, and it was suggested that this was either a dominant condition or the heterozygous expression of an X-linked entity (Fryns et al., 1988). In a subsequent report, a family with X-linked mental retardation was described in which the affected members had macrocephaly with heterozygous expression (Turner et al., 1994).

Unilateral macrocephaly is an unusual variant of macrocephaly, in which there is enlargement of only one cerebral hemisphere. It is due to abnormal neuronal cell migration in utero. It is usually associated with severe seizures during the neonatal period. The term macrocephaly is rather simplistic in such cases, as the anomaly is more typical of a hamartomatous malformation than a simple hypertrophy (Bignami et al., 1968; Townsend et al., 1975). Unilateral macrocephaly seems to be equally distributed between the right and left sides (King et al., 1985; Robain et al., 1988).

Macrocephaly is an unusual prenatal finding with an unknown incidence.

Macrocephaly should be suspected in the presence of abnormally large head measurements (greater than 3 SD above the mean for gestational age), without evidence of hydrocephalus or intracranial masses. Sonography should confirm the absence of other fetal anomalies, particularly hydrocephalus, by the identification of a normal fetal lateral ventricle:hemisphere ratio. Magnetic resonance imaging (MRI) can be used as an adjunct to determine if the macrocephaly is isolated or complicated by other brain malformations (Parazzini et al., 2005).

Benign familial macrocephaly has rarely been diagnosed in utero. In one case report, the abnormally large head circumference was first noted at 32 weeks’ gestation, at which time the biparietal diameter was consistent with a gestational age of 39 weeks (DeRosa et al., 1989). As the pregnancy progressed, the head size increased proportionately with other fetal biometric parameters.

Sonographic findings in unilateral macrocephaly include enlargement of one cerebral hemisphere, a shift of the midline structures, and mild ipsilateral ventriculomegaly (Sandri et al., 1991; Ramirez et al., 1994).