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KEY POINTS

Key Points

  • Macrocephaly is defined as a head circumference greater than three standard deviations (SDs) above the mean for age and sex.

  • This disorder is rare, and the exact incidence is unknown.

  • The antenatal natural history has not been elucidated.

  • During the antepartum period, other causes of macrocephaly should be excluded such as hydrocephalus or intracranial space-occupying lesion.

  • The diagnosis of macrocephaly should not alter prenatal care with regard to timing of delivery or mode of delivery.

  • Long-term outcome regarding macrocephaly is sparse. The majority of cases appear to do well; however, it appears to be associated with an increased risk for autism. Unilateral macrocephaly seems to be associated with poor outcomes.

  • The inheritance pattern of benign macrocephaly is autosomal dominant with incomplete penetrance with a male to female preponderance of 4:1. Differential diagnosis should include consideration of overgrowth syndromes, which may be due to single-gene disorders.

CONDITION

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).

Figure 18-1

Nine-year-old boy who exhibits macrocephaly as part of an overgrowth syndrome. His head circumference is 4 SD above the mean. (Photograph courtesy of Dr. Patricia Wheeler.)

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 ...

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