(See also Introduction to Congenital Craniofacial and Musculoskeletal Disorders Introduction to Congenital Craniofacial and Musculoskeletal Abnormalities Craniofacial and musculoskeletal abnormalities are common among children. They may involve only a single, specific site (eg, cleft lip, cleft palate, clubfoot) or be part of a syndrome of multiple... read more and Overview of Congenital Craniofacial Abnormalities Overview of Congenital Craniofacial Abnormalities Congenital craniofacial abnormalities are a group of defects caused by abnormal growth and/or development of the head and facial soft-tissue structures and/or bones. (See also Introduction to... read more .)
There are two types of macrocephaly:
Disproportionate macrocephaly
Proportionate macrocephaly
In disproportionate macrocephaly, the head is larger than appropriate for the child's size; affected children are at risk of autism spectrum disorders, developmental disability, and seizures.
In proportionate macrocephaly, the head appears appropriately sized for the body (ie, the large head is associated with a large stature), and an overgrowth syndrome (eg, growth hormone excess Gigantism and Acromegaly Gigantism and acromegaly are syndromes of excessive secretion of growth hormone (hypersomatotropism) that are nearly always due to a pituitary adenoma. Before closure of the epiphyses, the result... read more 
) should be considered.
Abnormal macrocephaly may be due to an enlarged brain (megalencephaly), hydrocephalus Hydrocephalus Hydrocephalus is accumulation of excessive amounts of CSF, causing cerebral ventricular enlargement and/or increased intracranial pressure. Manifestations can include enlarged head, bulging... read more 
, cranial hyperostosis, or other conditions. These conditions may be the result of genetic disorders or disorders the child acquired before or after birth (3 General references Macrocephaly (megacephaly) is a head circumference > 2 standard deviations above the mean for age ( 1, 2). (See also Introduction to Congenital Craniofacial and Musculoskeletal Disorders and... read more ).
General references
1. Cogulu O, Aykut A, Kutukculer N, et al: Two cases of macrocephaly and immune deficiency. Clin Dysmorphol 16(2):81–84, 2007. doi: 10.1097/MCD.0b013e3280464ee6
2. Fenichel, Gerald M: Clinical Pediatric Neurology: A Signs and Symptoms Approach, ed. 6. Philadelphia, Saunders/Elsevier, 2009, p. 369.
3. Strassburg HM: Macrocephaly is not always due to hydrocephalus. J Child Neurol 4 Suppl:S32–S40, 1989. doi: 10.1177/0883073889004001s07
Diagnosis
Prenatally, ultrasound
Postnatally, physical examination, including measurement of head circumference and cranial MRI
Genetic testing
Prenatally, the diagnosis of macrocephaly sometimes is made with routine ultrasonography done in the late second or early third trimester.
Postnatally, evaluation should include a 3-generation family history, developmental and neurologic assessment, 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 one parent has a large head circumference. The diagnoses to be considered include neurofibromatosis type 1 Neurofibromatosis Neurofibromatosis refers to several related disorders that have overlapping clinical manifestations but that are now understood to have distinct genetic causes. It causes various types of benign... read more 
, Fragile X syndrome Fragile X Syndrome Fragile X syndrome is a genetic abnormality on the X chromosome that leads to intellectual disability and behavioral disorders. Diagnosis is with molecular DNA analysis. Treatment is supportive... read more , Sotos syndrome, and lysosomal storage disorders Overview of Lysosomal Storage Disorders Lysosomal enzymes break down macromolecules, either those from the cell itself (eg, when cellular structural components are being recycled) or those acquired outside the cell. Inherited defects... read more .
A clinical geneticist should evaluate affected patients even in cases of apparent isolated congenital anomaly. Chromosomal microarray analysis Diagnosis Chromosomal anomalies cause various disorders. Anomalies that affect autosomes (the 22 paired chromosomes that are alike in males and females) are more common than those that affect sex chromosomes... read more , specific gene tests, or broader gene panel tests should be considered in the evaluation of patients with macrocephaly. If the results of these tests are nondiagnostic, whole exome sequencing analysis is recommended.
Developmental assessment should be done to identify need for any intervention to optimize developmental outcome.
Treatment
Surgical repair
Currently, the majority of these craniofacial anomalies are treated surgically with the goal or restoring function and improving cosmetic appearance. Treatment and management is 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.
