Microcephaly generally is due to the diminished size of the largest part of the human brain, the cerebral cortex, and the condition can arise during embryonic and fetal development due to insufficient neural stem cell proliferation, impaired or premature neurogenesis, the death of neural stem cells or neurons, or a combination of these factors. Research in animal models such as rodents has found many genes that are required for normal brain growth. For example, the Notch pathway genes regulate the balance between stem cell proliferation and neurogenesis in the stem cell layer known as the ventricular zone, and experimental mutations of many genes can cause microcephaly in mice, similar to human microcephaly. Mutations of the abnormal spindle-like microcephaly-associated (ASPM) gene are associated with microcephaly in humans and a knockout model has been developed in ferrets that exhibits severe microcephaly. In addition, viruses such as cytomegalovirus (CMV) or Zika have been shown to infect and kill the primary stem cell of the brain—the radial glial cell, resulting in the loss of future daughter neurons. The severity of the condition may depend on the timing of infection during pregnancy. Microcephaly is a feature common to several different genetic disorders arising from a deficiency in the cellular DNA damage response. Individuals with the following DNA damage response disorders exhibit microcephaly: Nijmegen breakage syndrome, ATR-Seckel syndrome, MCPH1-dependent primary microcephaly disorder, xeroderma pigmentosum complementation group A deficiency, Fanconi anemia, ligase 4 deficiency syndrome and Bloom syndrome. These findings suggest that a normal DNA damage response is critical during brain development, perhaps to protect against induction of apoptosis by DNA damage occurring in neurons.
symptom of Angelman syndrome
symptom of Williams syndrome
symptom of Fragile X syndrome
symptom of Kallmann syndrome
symptom of Rotor syndrome
symptom of Buschke–Ollendorff syndrome
symptom of Prader–Willi syndrome
symptom of Lesch–Nyhan syndrome