Developmental Neuropathology
Chapter 3: Microcephaly
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Microcephaly: small head; also used to mean small brain regardless of head circumference.


Signals for cell proliferation and cell death are important in the sculpting of the size of the brain. Many genes involved in neuroblast differentiation, neuronal fate, axon guildance, dendritic polarization and growth, and synaptic development.

Primary microcephaly

Head circumference >3 standard deviations below age and sex related mean, without any associated malformations or triggers.

Micro(en)cephaly vera and microcephaly with simplified gyral pattern

Micro(en)cephaly vera: small brains with no gross abnormalities. Depletion of germinal periventricular cells and neurons in cortical layers II and III. Could be due to premature exhaustion of neuronal progenitors in the germinal layer.

Micro(en)cephaly with abnormal or simplified gyral pattern: oligogyric microcephaly, micro-lissencephaly. Abnormal allocortical architechture, cmmon periventricular heterotopia.

Primary autosomal recessive microcephaly (MCPH)

Primary autosomal dominant microcephaly

Several families with normal intelligence reported.

X-linked microcephaly

Microcephaly in chromosomal syndromes

Other syndromes with congenital microcephaly

A number of autosomal recessive conditions have microcephaly. Some examples:

Genetic disorders with post-natal progressive microcephaly

Normal at birth, develop neurological symptoms and progressive microcephaly. Includes a number of metabolic disorders.

Secondary (non-genetic) microcephaly


Lissencephaly, holoprosencephaly, and other cerebral malformations usually result in microcephaly.

Clinical features

Variable, from normal intelligence to profound mental retardation. Need to look for consanguinity, risk factors during pregnancy and postnatally.

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