Macrocephaly - Causes

Causes

Macrocephaly may be pathologic, but many people with an unusually large head are healthy. Pathologic macrocephaly may be due to megalencephaly (enlarged brain), hydrocephalus (water on the brain), cranial hyperostosis (bone overgrowth), and other conditions. Pathologic macrocephaly is called "syndromic" when it is associated with any other noteworthy condition, and "nonsyndromic" otherwise. Pathologic macrocephaly can be caused by congenital anatomic abnormalities, genetic conditions, or by environmental events.

Many genetic conditions are associated with macrocephaly, including familial macrocephaly, autism, PTEN mutations such as Cowden disease, neurofibromatosis type 1, and tuberous sclerosis; overgrowth syndromes such as Sotos syndrome (cerebral gigantism), Weaver syndrome, Simpson-Golabi-Behmel syndrome (bulldog syndrome), and macrocephaly-capillary malformation (M-CMTC) syndrome; neurocardiofacial-cutaneous syndromes such as Noonan syndrome, Costello syndrome, and cardiofaciocutaneous syndrome; Fragile X syndrome; leukodystrophies (brain white matter degeneration) such as Alexander disease, Canavan disease, and megalencephalic leukoencephalopathy with subcortical cysts; and glutaric aciduria type 1 and D-2-hydroxyglutaric aciduria.

At one end of the genetic spectrum, duplications of chromosomes have been found to be related to autism and macrocephaly; at the other end, deletions of chromosomes have been found to be related to schizophrenia and microcephaly.

Environmental events associated with macrocephaly include infection, neonatal intraventricular hemorrhage (bleeding within the infant brain), subdural hematoma (bleeding beneath the outer lining of the brain), subdural effusion (collection of fluid beneath the outer lining of the brain), and arachnoid cysts (cysts on the brain surface).