The epidemiology, perinatal risk factors, and major neurologic comorbidity of 42 children with hydrocephalus were studied in a community-based clinic for children with neurodevelopmental disabilities at the Institute for Child Development, Tel Aviv, Israel. Of 4,309 children examined, 62 (1.4%) had macrocephaly (HC >98th percentile), of whom 42 (1%) had macrocephaly not associated with hydrocephalus. Of the 42, 3 had familial macrocephaly and 15 had comorbid diagnoses: generalized macrosomia in 6, of whom 3 had cerebral gigantism (Soto’s syndrome), migration defects (2), holoprosencephaly (1), neurofibromatosis type 1 (1), achondroplasia (2), myotonic dystrophy (1), and other (2). In comparison with normocephalic disabled controls, children with macrocephaly without hydrocephalus had an increased incidence of neonatal respiratory distress (9.5% vs 3.6%, p=0.042); other perinatal complications were not significantly different in the 2 groups. In the 42 patients with macrocephaly without hydrocephalus the risk of developing epilepsy or febrile seizures was significantly increased compared with controls (24% and 10% [p<0.001 and p=0.026] respectively). Macrocephaly was a significant risk factor for febrile seizures (odds ratio = 3.1, p<0.001) and epilepsy (odds ratio = 7.7, p<0.001), but not for mental retardation (odds ratio =1.1, p=0.78) or cerebral palsy (odds ratio = 1.3, p=0.67). [1]

COMMENT. Macrocephaly in children with diabilities, even when not associated with hydrocephalus, is associated with an increased risk of seizures. In addition to hydrocephalus, causes for macrocephaly include true megalencephaly, subdural effusion, pseudotumor cerebri, and familial variant. Megalencephaly may be a hamatomatous malformation, or is associated with metabolic CNS diseases (leukodystrophies and lipidoses), neurocutaneous syndromes, Sotos’ syndrome, and achondroplasia.

Lorber (1981) reported on a series of 510 children hospitalized because of macrocephaly. Of these, 75% had increased intracranial pressure, and 20% had primary megalencephaly. In children with megalencephaly, the male to female ratio was 4 to 1, familial incidence was 50%, and intellectual retardation and abnormal neurologic findings occurred in 13%. Abnormal head growth occurred mainly in the first 4 months.

Macrocephaly and epidural mass with acute lymphoblastic leukemia are reported in a 2-year-old female. Chemotherapy led to remission of ALL and MRI resolution of the mass. Macrocephaly may be a rare and early manifestation of leukemia. [2]