From the Guidelines
Macrocephaly is a condition that requires prompt medical evaluation to determine its underlying cause, as it can be associated with various conditions, including hydrocephalus, brain tumors, or genetic disorders, and its prognosis depends entirely on the underlying cause. Macrocephaly is typically defined as a head circumference above the 97th or 98th percentile for age and sex [ 1 ]. It can be benign and familial, or it may indicate an underlying condition that requires medical attention. When macrocephaly is identified, a medical evaluation is recommended, particularly in children, to determine the cause. This evaluation typically includes measuring head circumference accurately, reviewing growth patterns, and possibly neuroimaging studies like MRI or CT scans [ 1 ].
Causes and Associations
Macrocephaly can be associated with various conditions, including:
- Hydrocephalus
- Brain tumors
- Genetic disorders, such as PTEN mutations [ 1 ]
- Megalencephaly, which refers to an increase in size of the brain [ 1 ]
- Skeletal dysplasia [ 1 ]
Diagnostic Work-up
The diagnostic work-up for macrocephaly may include:
- Measuring head circumference accurately
- Reviewing growth patterns
- Neuroimaging studies, such as MRI or CT scans [ 1 ]
- Genetic testing, such as testing for PTEN mutations [ 1 ]
Prognosis and Management
The prognosis for macrocephaly depends entirely on the underlying cause. Benign familial macrocephaly has an excellent prognosis, while other causes may require specific treatments addressing the underlying condition [ 1 ]. Regular monitoring of head growth and development is important for children with macrocephaly to ensure early intervention if needed. In some cases, macrocephaly may be associated with an increased risk of malignancies, particularly in the context of overgrowth syndromes, such as PTEN hamartoma tumor syndrome [ 1 ].
Recent Recommendations
Recent consensus recommendations suggest that the diagnostic work-up for malformations of cortical development, including macrocephaly, should include a standardized workflow, including genetic testing and neuroimaging studies [ 1 ]. The identification of the underlying cause of macrocephaly is crucial for determining the prognosis and management of the condition.
From the Research
Definition and Classification of Macrocephaly
- Macrocephaly is defined as a head circumference above the 98th percentile or greater than +2SD above the mean for gestational age 2.
- It can be primary, due to increased brain tissue (megalocephaly), or secondary, due to various causes such as hydrocephalus, cerebral edema, or brain tumors 2, 3.
- Megalocephaly can be syndromic or non-syndromic, with gyral and structural CNS anomalies common in the former 2.
Causes and Diagnosis of Macrocephaly
- The cause of macrocephaly can be benign in many cases, but it can also be life-threatening, and prompt recognition and timely diagnosis are crucial for a better prognosis 4.
- The differential diagnosis for macrocephaly is broad and includes conditions such as communicating or non-communicating hydrocephalus, cerebral edema, and brain tumors 2, 3.
- Neuroimaging plays an important role in the evaluation of macrocephaly, especially in the metabolic subtype, which may not be overtly apparent clinically 3.
- A systematic approach to pediatric macrocephaly involves identifying which of the four components of the cranium (cerebrospinal fluid, blood and vasculature, brain parenchyma, or calvarium) has an increased volume 5.
Genetic Disorders Associated with Macrocephaly
- Macrocephaly is associated with many genetic disorders, including familial macrocephaly, autism spectrum disorders, leukodystrophies, and organic acidurias 6.
- The genetic macrocephaly conditions cover a broad spectrum of gene disorders, and their related proteins have diverse biological functions 6.
- Genetic testing may be necessary for some cases of macrocephaly, especially those with a family history or suspicious clinical features 6, 5.
Evaluation and Management of Macrocephaly
- A clinicoradiological algorithm for evaluation of macrocephaly involves considering patient age, additional imaging findings, and clinical symptoms 3.
- Multiple imaging modalities, including US, CT, and MRI, are complementary in evaluating macrocephaly 5.
- The degree of macrocephaly is important, with mild macrocephaly ≤2.5SD carrying a good prognosis, especially when one of the parents has macrocephaly and normal development 2.