Microcephaly

Key Features

• Head circumference more than 2 standard deviations below the mean for age and sex

• Nearly always associated with developmental delay and learning difficulties

• Primary microcephaly is present at birth

• Secondary microcephaly develops postnatally

Clinical Findings

• May be suspected in the full-term newborn and in infants up to age 6 months whose chest circumference exceeds the head circumference (unless the child is very obese)

• May be discovered when the child is examined because of delayed developmental milestones or neurologic problems, such as seizures or spasticity

• May be a marked backward slope of the forehead (as in familial microcephaly) with narrowing of the bitemporal diameter

• Eye, cardiac, and bone abnormalities may also be clues to congenital infection

Diagnosis

• Laboratory findings vary with the cause

• In the newborn, congenital infection may be assessed by

  • IgM antibody titers for toxoplasmosis, rubella, cytomegalovirus (CMV), herpes simplex virus, and syphilis

  • Urine culture for CMV

• Genetic testing can be targeted based on history and physical examination

• Most metabolic disorders present either as congenital syndromic microcephaly (ie, dysmorphisms present on examination) or with postnatal microcephaly and global developmental delay

• Nonsyndromic microcephaly presenting at birth may be due to

  • Maternal PKU (maternal serum with elevated phenylalanine)

  • Phosphoglycerate dehydrogenase deficiency (disorder of L-serine biosynthesis)

  • Amish lethal microcephaly (elevated urine alpha-ketoglutaric acid)

• CT or MRI scans

  • May demonstrate calcifications, malformations, or atrophic patterns that suggest specific congenital infections or genetic syndromes

  • MRI is most helpful in definitive diagnosis, prognosis, and genetic counseling

• Plain skull radiographs are of limited value

Treatment

• Genetic counseling should be offered to the family of any infant with significant microcephaly

• Individuals may need screening for vision and hearing abnormalities as well as supportive therapies for developmental delay