Macrocephaly is a head circumference > 2 standard deviations above the mean for age and sex (1). Megalencephaly is enlargement of the brain parenchyma itself.
The prevalence of macrocephaly at or near birth using the World Health Organization (WHO) reference standards is approximately 7% but varies widely by geographic region (1 to 10%) (2). Macrocephaly may be benign and hereditary, but it can also be associated with underlying brain anomalies, vascular anomalies, and numerous genetic syndromes (3, 4). (See also Overview of Congenital Craniofacial Anomalies.)
Megalencephaly is due to an enlarged brain that results from an increased number of neuronal cells (eg, an overgrowth syndrome) or from abnormal accumulation of substances in the brain (eg, metabolic disorders) (1). Hydrocephalus, cranial hyperostosis, autism spectrum disorder, increased intra-cranial pressure, seizures, and other conditions can occur with megalencephaly. These conditions may be the result of genetic disorders or disorders the child acquired before or after birth (5).
General references
1. Tan AP, Mankad K, Gonçalves FG, Talenti G, Alexia E. Macrocephaly: Solving the Diagnostic Dilemma. Top Magn Reson Imaging. 2018;27(4):197-217. doi:10.1097/RMR.0000000000000170
2. Hui LL, Ho FK, Wright CM, et al. World variation in head circumference for children from birth to 5 years and a comparison with the WHO standards. Arch Dis Child. 2023;108(5):373-378. doi:10.1136/archdischild-2022-324661
3. Shinar S, Chitayat D, Shannon P, Blaser S. Fetal macrocephaly: Pathophysiology, prenatal diagnosis and management. Prenat Diagn. 2023;43(13):1650-1661. doi:10.1002/pd.6473
4. Guerrini R, Dobyns WB. Malformations of cortical development: clinical features and genetic causes. Lancet Neurol. 2014;13(7):710-726. doi:10.1016/S1474-4422(14)70040-7
5. Williams CA, Dagli A, Battaglia A. Genetic disorders associated with macrocephaly. Am J Med Genet A. 2008;146A(15):2023–2037. doi:10.1002/ajmg.a.32434
Diagnosis of Macrocephaly
Prenatally, ultrasound
Postnatally, physical examination, including measurement of head circumference and sometimes cranial MRI or ultrasound
Sometimes genetic testing
Prenatally, the diagnosis of macrocephaly and megalencephaly sometimes is made with a routine ultrasound performed in the late second or early third trimester.
Postnatally, the diagnosis depends on accurate measurements of the head circumference (measured at the most prominent part on the back of the occiput and just above the supraorbital ridges). Evaluation should include a 3-generation family history, developmental and neurologic assessment, dysmorphology examination, examination for limb asymmetry and cutaneous lesions, and brain MRI. Sometimes disproportionate macrocephaly is familial and not associated with other anomalies, complications, or developmental delays; this form is transmitted in an autosomal dominant pattern, and may not need imaging (1, 2). Ultrasound may also be useful as an imaging modality (3). There are numerous diagnoses to be considered, including neurofibromatosis type 1, Fragile X syndrome, Sotos syndrome, metabolic disorders, and lysosomal storage disorders.
A clinical geneticist should evaluate affected patients even in cases of apparent isolated congenital anomaly. Chromosomal microarray analysis, specific gene tests, or broader gene panel tests should be considered in the evaluation of patients with macrocephaly or megalencephaly. Clinical exome sequencing is the first-tier test if there is underlying developmental delay or intellectual disability (4). If negative, clinical genome sequencing analysis may be recommended.
Developmental assessment should be performed to identify the need for early intervention and to optimize developmental outcome.
Diagnosis references
1. Sampson MA, Berg AD, Huber JN, Olgun G. Necessity of Intracranial Imaging in Infants and Children With Macrocephaly. Pediatr Neurol. 2019;93:21-26. doi:10.1016/j.pediatrneurol.2018.10.018
2. Haws ME, Linscott L, Thomas C, Orscheln E, Radhakrishnan R, Kline-Fath B. A Retrospective Analysis of the Utility of Head Computed Tomography and/or Magnetic Resonance Imaging in the Management of Benign Macrocrania. J Pediatr. 2017;182:283-289.e1. doi:10.1016/j.jpeds.2016.11.033
3. Thomas CN, Kolbe AB, Binkovitz LA, McDonald JS, Thomas KB. Asymptomatic macrocephaly: to scan or not to scan. Pediatr Radiol. 2021;51(5):811-821. doi:10.1007/s00247-020-04907-7
4. Rodan LH, Stoler J, Chen E, Geleske T; Council on Genetics. Genetic Evaluation of the Child With Intellectual Disability or Global Developmental Delay: Clinical Report. Pediatrics. 2025;156(1):e2025072219. doi:10.1542/peds.2025-072219
Treatment of Macrocephaly
Treatment of the cause
Sometimes surgical repair
Surgical treatment of macrocephaly depends upon the cause. For example, hydrocephalus requires a shunt; brain tumors may require resection. Benign familial macrocephaly does not typically require surgical treatment (1, 2).
When treated surgically the goals are restoring function and improving cosmetic appearance. Treatment and management are best done in tertiary medical centers by multidisciplinary teams capable of addressing all symptoms caused by the congenital anomaly.
Secondary complications (eg, increased intracranial pressure, amblyopia, dental misalignments, speech difficulties) should be managed by the appropriate specialists. Targeted medications may be used depending on the underlying cause of the macrocephaly.
There is no cure for megalencephaly, but treatment can help with seizures or other symptoms.
Treatment references
1. Haws ME, Linscott L, Thomas C, Orscheln E, Radhakrishnan R, Kline-Fath B. A Retrospective Analysis of the Utility of Head Computed Tomography and/or Magnetic Resonance Imaging in the Management of Benign Macrocrania. J Pediatr. 2017;182:283-289.e1. doi:10.1016/j.jpeds.2016.11.033
2. Thomas CN, Kolbe AB, Binkovitz LA, McDonald JS, Thomas KB. Asymptomatic macrocephaly: to scan or not to scan. Pediatr Radiol. 2021;51(5):811-821. doi:10.1007/s00247-020-04907-7
