Microcephaly can only be diagnosed when the head circumference is more than 2 standard deviations (S.D.) below that of normal children.

There are many causes of microcephaly. Various harmful factors during early pregnancy (infection, malnutrition, poisoning, radiation) may affect the development of the fetal brain. Metabolic abnormalities, chromosomal aberrations (such as trisomy 21, trisomy 18, trisomy 13, or other abnormalities) are often associated with microcephaly, as are some familial hereditary forms. Various causes at birth or postnatally (hypoxia, infection, trauma) can also lead to brain injury and atrophy, resulting in a smaller head circumference, known as secondary microcephaly.

In some cases of microcephaly, the brain is small but morphologically normal, while in others, there are obvious malformations or enlarged ventricles.

Affected children have a small and pointed vertex, narrow forehead, small cranial vault, flat occiput, and relatively large facial features and ears. The anterior fontanelle and sutures close prematurely, and there may be interosseous ridges.

Children with microcephaly often exhibit delayed physical and intellectual development, though not all cases are associated with intellectual disability. Approximately 7.5% of children with a head circumference 2–3 standard deviations below normal have normal intelligence. Some children may also experience seizures and/or cerebral palsy. CT scans may reveal brain atrophy, widened ventricles, and subarachnoid spaces, or simply a small brain volume with otherwise normal structures.

Another syndrome that can also present with a small head is Rett syndrome. According to the diagnostic criteria established at the 1984 Vienna International Symposium, the features are as follows: (1) Affects girls; (2) Normal prenatal and perinatal periods, with normal neuropsychiatric and motor development for the first 6–18 weeks after birth; (3) Essentially normal head circumference at birth, followed by progressive developmental delay leading to microcephaly between 6 months and 4 years of age; (4) Gradual intellectual regression and reduced social interaction between 1.5 and 4 years of age; (5) Loss of acquired hand skills between 1 and 4 years, accompanied by repetitive, stereotyped hand-wringing, washing, or twisting movements, along with episodes of hyperventilation, teeth grinding, or staring; (6) Reduced walking, altered gait, or ataxia; (7) The course may include stable periods, followed by the onset of epilepsy and pyramidal signs. The disease cause of this syndrome is unclear, and there is no specific treatment.