Neurocutaneous Disorders
The possibility of a neurocutaneous disorder should be considered in every neonate with macrocephaly. The evaluation of every neonate with macrocephaly should include a careful cutaneous examination. The two neurocutaneous disorders most often associated with macrocephaly are hypomelanosis of Ito and linear nevus sebacceous syndrome.

Soto Syndrome
Neonates with Soto syndrome are born with borderline macrocephaly. The diagnosis of this disorder is established by the presence of a growth spurt beyond the normal range during the first 3 years of life. This excessive growth spurt causes the infant to become larger than normal, especially the head. Plasma somatomedin levels are usually elevated during the growth spurt. Soto syndrome is usually a sporadic condition, although familial cases have been reported. Estrogen may reduce growth in girls.

Metabolic Megalencephalies
Metabolic megalencephalies do not usually present in the neonatal period. The exceptions to this are glutaric acidemia type I, Canavan disease, and Alexander disease.