What is the appropriate method to diagnose parental macrocephaly?

Diagnosing Parental Macrocephaly

Measure both parents' occipitofrontal circumference (OFC) using a firm, non-stretchable measuring tape with sufficient tension to compress hair against the skull, recording to the nearest 0.1 cm; parental macrocephaly is defined as OFC ≥2 standard deviations (≥58 cm in adult women, ≥60 cm in adult men) above the mean. 1, 2

Measurement Technique

• Use proper equipment and technique: Apply a firm, non-stretchable measuring tape around the largest circumference of the head, with sufficient tension to compress hair against the skull 1
• Record precisely: Document measurements to the nearest 0.1 cm for accuracy 1
• Measure both parents: This is essential when evaluating an infant with macrocephaly, as recommended by the American Academy of Pediatrics 1

Diagnostic Thresholds

• Macrocephaly definition: OFC ≥2 standard deviations above the mean for age and sex 3
• Specific adult cutoffs: ≥58 cm in adult women and ≥60 cm in adult men represents the 97th percentile (macrocephaly threshold) 3
• Clinical significance: When one or both parents have macrocephaly and the infant also has an enlarged head, this suggests benign familial megalencephaly 1, 2

Confirming Benign Familial Megalencephaly

Once parental macrocephaly is documented, the following features support benign familial megalencephaly in the child:

• Normal fontanels on physical examination 1
• Normal motor development without delays 1
• Absence of signs of increased intracranial pressure (no bulging fontanel, vomiting, lethargy, or papilledema) 1
• Structurally normal brain on MRI - this is mandatory to confirm the diagnosis and exclude hydrocephalus or structural abnormalities 1, 2
• Stable growth trajectory on serial head circumference measurements 1, 2

Critical Pitfalls to Avoid

• Never reassure families based solely on parental measurements: Even with documented parental macrocephaly, MRI is mandatory to exclude pathological causes 1, 2
• Do not skip neuroimaging: A structurally normal brain must be confirmed by MRI according to the American Academy of Neurology 1
• Avoid single measurements: Serial head circumference assessments are essential to ensure stable growth patterns rather than accelerating growth 1, 2
• Measure promptly: Parental head circumferences should be obtained early in the evaluation, as familial patterns are the most common benign cause 2

When Parental Macrocephaly Does NOT Explain the Child's Presentation

Even if parents have macrocephaly, further investigation is warranted when:

• Severe macrocephaly (>3-4 standard deviations above the mean) is present in the child 2
• Dysmorphic features or multiple congenital anomalies are present 2
• Neurocutaneous stigmata (café-au-lait spots, hypopigmented macules, vascular lesions) are identified 2
• Developmental delays or regression occur 4
• Seizures or focal neurological deficits develop 4

In these scenarios, genetic testing (PTEN analysis, chromosomal microarray, or deep sequencing for mTOR pathway genes) should be pursued despite parental macrocephaly 2, 4