Microcephaly usually begins with too few brain stem cells in the womb
A smaller-than-normal head is the visible sign, but the underlying story of microcephaly is about the cerebral cortex failing to grow. Too few neural stem cells, neurons made too early, or stem cells destroyed by viruses such as Zika can all leave the developing brain short of the cells it needs.
Microcephaly, from Greek words meaning small head, may be present at birth or appear in the first years of life. Definitions vary, but it is usually diagnosed when head circumference falls more than two standard deviations below the average for age and sex; some researchers argue for a stricter threshold of three. In the United States it is reported in somewhere between 1 in 800 and 1 in 5,000 births. Outcomes range widely, from severe intellectual disability and seizures to, occasionally, normal intelligence alongside a persistently small head.
Most cases trace back to genes, though often no specific cause is found. A family of genes labelled MCPH, named after the first, microcephalin, governs brain size; when one is mutated, the result can be primary microcephaly with few other symptoms. One of them, ASPM, has been knocked out in ferrets, producing severe microcephaly. Common, harmless variants in some of the same genes are linked to normal differences in cortical surface area and brain volume on MRI scans. Several disorders of DNA repair also cause the condition, hinting that developing neurons need strong protection against genetic damage.
Outside influences matter too. Alcohol in pregnancy and infections passed from mother to fetus can disrupt brain growth. Cytomegalovirus and Zika can infect and kill radial glial cells, the brain's main stem cells, so the neurons they would have produced never form. Health bodies including the US Centers for Disease Control and Prevention linked the spread of mosquito-borne Zika to rising rates of congenital microcephaly. Radiation is another cause: of 11 women who were 11 to 17 weeks pregnant and within 1.2 km of the Hiroshima blast, 7 had children with microcephaly.
No treatment restores normal head size, and care focuses on symptoms, although cases linked to amino acid deficiencies have improved with supplements. History was often cruel: in the 19th and early 20th centuries, people with the condition were sold to freak shows and billed as missing links.
Source: Microcephaly
