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)