An MRI of a patient with benign familial macrocephaly (male with head circumference > 60cm)
|Classification and external resources|
Macrocephaly (derived from the ancient Greek adjective μακροκέφαλος makroképhalos, "long-headed", composed of the words μακρός makros, "long" + κεφαλή kephalé, "head"), occurs when the head is abnormally large (2.5 standard deviations above normal for weight and gender) ; this includes the scalp, the cranial bone, and the contents of the cranium.
Macrocephaly may be pathologic, but many people with an unusually large head and large skull 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 related to the holgate gene, 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).
Macrocephaly is customarily diagnosed if head circumference is greater than two standard deviations (SDs) above the mean. Relative macrocephaly occurs if the measure is less than two SDs above the mean, but is disproportionately above that when ethnicity and stature are considered. In research, cranial height or brain imaging is also used to determine intracranial volume more accurately.
- Williams CA, Dagli A, Battaglia A (2008). "Genetic disorders associated with macrocephaly". Am J Med Genet A 146A (16): 2023–37. doi:10.1002/ajmg.a.32434. PMID 18629877.
- http://www.pnas.org/content/107/suppl.1/1736.full Crespi et al. Comparative genomics of autism and schizophrenia; 1736-1741; PNAS; January 26, 2010; vol. 107; suppl. 1
- Rare chromosomal deletions and duplications increase risk of schizophrenia; The International Schizophrenia Consortium; Nature 455, 237-241 (11 September 2008) | doi:10.1038/nature07239; Received 14 May 2008; Accepted 8 July 2008; Published online 30 July 2008
- L. Dumas and J.M. Sikela; DUF1220 Domains, Cognitive Disease, and Human Brain Evolution; Advance 2009, doi:10.1101/sqb.2009.74.025; Cold Spring Harbor Laboratory Press
- GeneReviews/NCBI/NIH/UW entry on PTEN Hamartoma Tumor Syndrome (PHTS)
- GeneReviews/NCBI/NIH/UW entry on 9q22.3 Microdeletion