Macrocephaly is a head circumference > 2 standard deviations above the mean for age (1). Megalencephaly is enlargement of the brain parenchyma itself.
(See also Overview of Congenital Craniofacial Anomalies.)
Macrocephaly may be benign and hereditary, but it can also be associated with underlying brain anomalies, vascular anomalies, and numerous genetic syndromes.
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 (2).
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. 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 cranial MRI
Genetic testing
Prenatally, the diagnosis of macrocephaly and megalencephaly sometimes is made with a routine ultrasound done 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, so at least 1 parent has a large head circumference. 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. If the results of these tests are nondiagnostic, whole exome sequencing analysis may be recommended.
Developmental assessment should be done to identify the need for any intervention and to optimize developmental outcome.
Treatment of Macrocephaly
Surgical repair
Currently, most cases of macrocephaly are treated surgically with the goal of 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.
