Prevalence:

• 1 in 1,000 births.
• 80% of affected infants have a normal head circumference at birth and 90% of affected individuals had a normal head circumference in the second trimester.

Ultrasound diagnosis:

• Ultrasound diagnosis is made usually in the late second and third trimesters.
• The fetal head circumference to abdominal circumference ratio is below the 3^rd percentile (2 standards deviations below the normal mean for gestational age).
• There is slopping forehead due to the disproportion of the frontal lobes and the face.
• In most cases presenting in the second trimester there is associated holoprosencephaly or encephalocele and in those presenting in the third trimester there are abnormalities of sulcation or neuronal migration.

Associated abnormalities:

• Chromosomal abnormalities are rare and the most common are trisomies 13, 18 and 21.
• Genetic syndromes are very common, most of them being caused by single gene defects with either autosomal recessive or X linked patterns of inheritance. The most common are: Meckel-Gruber, Walker-Walburg, Miller-Diecker, Smith-Lemli-Opitz, Seckel syndrome.

Investigations:

• Detailed ultrasound examination, including neurosonography.
• Invasive testing for karyotyping and array.
• TORCH test for fetal infections.
• Fetal brain MRI at ≥32 weeks’ gestation for diagnosis of abnormalities of neuronal migration, such as lissencephaly and polymicrogyria.

Follow up:

• Ultrasound scans every 4 weeks to monitor the evolution of head circumference.

Delivery:

• Standard obstetric care and delivery.

Prognosis:

• Isolated: the risk of neurodevelopmental delay inreases with decreasing head circumference from 10% if the circumference is 2 to 3 standard deviations (SD) below the normal mean for gestational age, to 100% if >4 SD's.
• Syndromic: the prognosis depends on the underlying condition.

Recurrence:

• No associated structural defects: 5-10%.
• Familial form of isolated microcephaly: 25%.