Background
Macrocephaly is defined as head circumference more than two standard deviations (SD) above the mean value for a given age and gender. [1] It has to be differentiated from megalencephaly, which is defined as increase in the size of the brain parenchyma. Head circumference is measured to monitor head growth in infants and children. It is also known as occipitofrontal circumference (OFC) and it denotes the size of the cranium. Macrocephaly can be the first manifestation of various congenital and acquired neurologic conditions or may be just a familial trait. [2] The images below show an infant with this condition.
Pathophysiology
Macrocephaly can result from enlargement of the skull bones or an increase in the volume of the intracranial structures like cerebrospinal fluid, blood, or the brain parenchyma itself (megalencephaly). It may be secondary to raised intracranial pressure or space-occupying lesions. It can also be a feature of various congenital syndromes and is then referred to as syndromic macrocephaly. The pathogenesis is therefore cause-dependent.
Epidemiology
Macrocephaly is a relatively rare condition but has multiple etiologies, therefore the incidence and prevalence has not been documented by many studies. However, one community-based study in Israel quoted a prevalence of 1.4%. [3] There is no gender or racial predisposition.
Currently, World Health Organization (WHO) growth charts may incorrectly indicate high rates of macrocephaly in Inuit children from Nunavut, Canada, leading to unnecessary medical evaluations and travel burdens. Research suggests that using population-specific growth curves for Inuit children could lead to more accurate diagnoses of microcephaly and reduce overdiagnosis of macrocephaly. This finding highlights the importance of considering population-specific growth patterns in medical assessments, especially for Indigenous populations. [4]
Prognosis
The outcome and prognosis of macrocephaly depends on the cause. The prognosis is quite favorable in children with benign familial macrocephaly.
Patient Education
The following link is provided to assist you in educating your patients about their condition. This resource can be used as a starting point to help your patients learn about their health and make informed care decisions.
Etiology
The etiology of macrocephaly is diverse. [5] The most common cause is benign familial macrocephaly characterized by enlargement of the subarachnoid spaces and accounts for almost 50% of cases.
Other causes are described below.
Enlargement of skull bones
- Hyperostosis cranii - associated with disorders such as osteogenesis imperfecta, achondroplasia, and osteopetrosis
- Secondary enlargement due to bone marrow expansion - as seen in thalassemia major
Increase in volume of cerebrospinal fluid
- Hydrocephalus
- Choroid plexus papilloma
- Benign familial macrocephaly
Megalencephaly
- Leukodystrophies - Canavan disease, Alexander disease, megalencephalic leukoencephalopathy with subcortical cysts
- Lysosomal storage disorders - Tay-sachs, mucopolysaccharoidosis, gangliosidosis
- Neurocutaneous disroders - Tuberous sclerosis, Sturge-weber syndrome, neurofibromatosis, Gorlin syndrome
- Autism spectrum disorder
- Other syndromes - Fragile X syndrome, Cowden syndrome, Sotos syndrome
Increased intracranial pressure (ICP)
- CNS infections
- Pseudotumor cerebri
- Subdural collections including hygromas
Mass lesions and increase in volume of blood
- Tumor
- Intraventricular hemorrhage, subdural hematoma, arteriovenous malformation
-
A 1-year-old boy with macrocephaly. The image illustrates the increased head circumference (large head).
-
A 1-year-old boy with macrocephaly. The image illustrates the increased head circumference (large head).
-
A 1-year-old boy with macrocephaly. The image illustrates the increased head circumference (large head).
-
Antero-posterior and lateral views on skull radiographs of a 1-year-old boy with macrocephaly.
-
Antero-posterior view on skull radiograph of a 1-year-old boy with macrocephaly.
-
Lateral view on skull radiograph of a 1-year-old boy with macrocephaly. The increased antero-posterior diameter can be appreciated.
-
Noncontrast CT scan of brain of a 2-year-old boy showing gross hydrocephalus with paper thin brain tissue (coronal view).
-
Noncontrast CT scan of brain of a 2-year-old boy showing gross hydrocephalus with paper thin brain tissue (coronal view).
-
Noncontrast CT scan of brain of a 2-year-old boy showing gross hydrocephalus with paper thin brain tissue (coronal view).
-
Noncontrast CT scan of brain of a 2-year-old boy showing gross hydrocephalus with paper thin brain tissue (coronal view).
-
Ventriculoperitoneal shunt in situ.