Head circumference below the 3rd percentile for age and sex

Specialty: Pediatrics.

• Infantile microcephaly
• decreased cranial size in children

Why it occurs

• Autosomal recessive genetic primary microcephaly (intrinsic disorder of neurodevelopment and cortical neurogenesis due to mutations in genes that regulate the mitotic spindle and centrosome during the division of neuronal progenitors)
• Congenital infections of the TORCH group (fetal infection by Cytomegalovirus, Toxoplasmosis, Rubella, Zika virus or Herpes Simplex, which produce destruction of the developing brain parenchyma, intracranial calcifications and secondary brain atrophy)
• Prenatal exposure to teratogenic or toxic substances (Fetal Alcohol Syndrome or FAS, use of cocaine, methotrexate, phenytoin or elevated levels of maternal phenylalanine due to poorly controlled phenylketonuria)
• Severe perinatal hypoxic-ischemic encephalopathy or intrauterine vascular insult (diffuse cortical neuronal necrosis with progressive loss of brain mass and secondary poor cranial bone growth)
• Complex syndromic craniosynostosis or microcephaly due to extreme sensory deprivation.

Initial workup

Precise measurement of the child's head circumference using a flexible, non-extendable measuring tape and comparison of the results with the WHO growth curves for age and sex (as well as the mandatory measurement of the head circumference of both parents to rule out autosomal dominant benign familial microcephaly). High-resolution Brain Magnetic Resonance (MRI) (the study of choice to assess cortical morphology, neuronal migration patterns, thickness of the corpus callosum, myelination and presence of calcifications or brain atrophy). Maternal and infant serologies for TORCH and Zika virus (IgM/IgG antibodies, urine PCR for CMV in the first 21 days of life). Molecular genetic study through comparative genomic hybridization by arrays (Array-CGH) or targeted sequencing panels.

Standard management

• There is no pharmacological treatment to stimulate the growth of the brain or cranial cavity; the pillar of treatment is based on multidisciplinary early care — physiotherapy, speech therapy, cognitive stimulation and occupational therapy). If epileptic seizures are associated: Phenobarbital (anticonvulsant of choice in the neonatal period; loading dose of 20 mg/kg IV, followed by maintenance doses of 3 to 5 mg/kg/day orally or IV
• Levetiracetam — anticonvulsant of choice in infants; dose of 10 to 60 mg/kg/day divided every 12 hours
• Valproic acid (dose of 15 to 40 mg/kg/day, monitoring liver function and ammonia).