Microcephaly & Macrocephaly

Primary prerequisite for the diagnosis of microcephaly/macrocephaly is the proper horizontal head circumference (HC) measurement (frontal-occipital circumference):

• supine position
• glabella – opisthocranion as anchor points
• normocephaly (32-38 cm for a term newborn) => refer to percentile graphs for your hospital, region or country
• percentile graphs for preterm population (Fenton graphs)
• sexual dimorphism at birth (1 cm)

Head circumference at birth is usually proportional to birth length in appropriate-for-gestational-age newborns. For asymmetrical IUGR (intrauterine growth restriction) infants, head circumference and length at birth is usually normal, as compared to their lower birth weight.

Microcephaly = head circumference < 3.percentile in the corresponding percentile growth charts for the specific patient (gestational and postnatal age, sex)

Macrocephaly = head circumference > 97.percentile (see above)

Etiology

Etiology – General

• measurement errors (make sure to measure anthropometric parameters precisely and if needed, perform serial measurements)
• false positive measurements (transient changes to the body area – breech delivery; instrumental delivery; head molding during birth; caput succedaneum; cephalhematoma)

Etiology – Macrocephaly

• hereditary / familiar
• hydrocephalus = abnormal accumulation of cerebrospinal fluid in the intracranial space
  • congenital (CNS malformations – stenosis of the Sylvian aqueduct; Chiari syndromes; Dandy-Walker syndrome; vascular malformations) – congenital hydrocephalus is often diagnosed prenatally (15-18 weeks of gestation)
  • acquired (post-hemorrhagic; post-infectious)
• achondroplasia
• inherited metabolic disorders (Alexander disease; infantile form of Krabbe disease; glutaric acidemia/aciduria I)
• genetic syndromes (neurofibromatosis von Recklinghausen I; Silver-Russell; Sotos; Sturge-Weber-Krabbe)
• scaphocephaly (premature fusion of the sagittal suture)

Etiology – Microcephaly

• hereditary / familiar
• congenital infection (TORCH – cytomegalovirus; herpetic viruses; rubella; varicella; toxoplasmosis)
• teratogens (alcohol – fetal alcohol syndrome; radiation before 15 weeks of gestation; phenytoin (anti-epileptic drug) – fetal hydantoin syndrome)
• congenital CNS anomalies (lissencephaly; cranial encephalocele/meningocele)
• numeric chromosomal abnormalities (Patau – trisomy 13; Edwards – trisomy 18; Down – trisomy 21)
• genetic syndromes (Bloom; Dubowitz; Nijmegen breakage syndrome; Prader-Willi; Rubinstein-Taybi; Seckel; Smith-Lemli-Opitz)
• other causes (maternal hyperphenylalaninemia; complex craniosynostosis)
• intrauterine hypoxic-ischemic insult

Diagnosis

Clinical signs

• Proper and serial head circumference measurement (see above) – rate of growth of HC > + 1.25 cm/week can be abnormal
• Features of deviation from the normal development (facial dysmorphism, other anomalies)
• Medical history (pregnancy; medication; extended family – anthropometric measurements in family)

Laboratory findings

• Biochemistry and hematology
  • inflammatory markers (CRP, procalcitonin, interleukin-6)
  • full blood count
  • biochemistry (urea, creatinine, liver function tests; ammonia; blood gas; phenylalanine in mother
  • inherited metabolic disorders (blood + urine + cerebrospinal fluid)
• Serology (IgM, IgG – blood + cerebrospinal fluid)
• PCR – DNA (TORCH – blood + urine + cerebrospinal fluid)
• Genetics (karyotype; micro-array; prenatal diagnosis can be done also from amniotic fluid or chorionic villi)
• Cerebrospinal fluid (biochemistry, cytology, culture, serology)

Imaging

• Cranial ultrasound (prenatal, postnatal)
• MRI (prenatal, postnatal)
• X-ray of skull
• Ophthalmology (fundus – chorioretinitis with TORCH infection – CMV, Toxoplasma)

Therapy

Surgery

• Craniosynostosis (remodelling to ensure optimal brain growth and to optimise neurocranium shape)
  • indicated and performed between 4-6 months of age
• Hydrocephalus (derivation of cerebrospinal fluid)
  • temporary (external reservoir = Ommaya reservoir)
  • permanent (internal reservoir = ventriculoperitoneal (VP) shunt)

References

① Leibovitz Z, Lerman-Sagie T. Diagnostic approach to fetal microcephaly. Eur J Paediatr Neurol. 2018;22(6):935-943. doi:10.1016/j.ejpn.2018.06.002