The Genetics of Primary Microcephaly

Annu Rev Genomics Hum Genet. 2018 Aug 31;19:177-200. doi: 10.1146/annurev-genom-083117-021441. Epub 2018 May 23.


Primary microcephaly (MCPH, for "microcephaly primary hereditary") is a disorder of brain development that results in a head circumference more than 3 standard deviations below the mean for age and gender. It has a wide variety of causes, including toxic exposures, in utero infections, and metabolic conditions. While the genetic microcephaly syndromes are relatively rare, studying these syndromes can reveal molecular mechanisms that are critical in the regulation of neural progenitor cells, brain size, and human brain evolution. Many of the causative genes for MCPH encode centrosomal proteins involved in centriole biogenesis. However, other MCPH genes fall under different mechanistic categories, notably DNA replication and repair. Recent gene discoveries and functional studies have implicated novel cellular processes, such as cytokinesis, centromere and kinetochore function, transmembrane or intracellular transport, Wnt signaling, and autophagy, as well as the apical polarity complex. Thus, MCPH genes implicate a wide variety of molecular and cellular mechanisms in the regulation of cerebral cortical size during development.

Keywords: DNA repair; centrosome; microcephaly; radial glial cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Centrioles / pathology
  • DNA Repair
  • DNA Replication
  • Genetic Predisposition to Disease*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Microcephaly / genetics*
  • Neuroglia / pathology


  • Intracellular Signaling Peptides and Proteins

Supplementary concepts

  • Autosomal Recessive Primary Microcephaly