Genetic disorders associated with postnatal microcephaly

Am J Med Genet C Semin Med Genet. 2014 Jun;166C(2):140-55. doi: 10.1002/ajmg.c.31400. Epub 2014 May 16.


Several genetic disorders are characterized by normal head size at birth, followed by deceleration in head growth resulting in postnatal microcephaly. Among these are classic disorders such as Angelman syndrome and MECP2-related disorder (formerly Rett syndrome), as well as more recently described clinical entities associated with mutations in CASK, CDKL5, CREBBP, and EP300 (Rubinstein-Taybi syndrome), FOXG1, SLC9A6 (Christianson syndrome), and TCF4 (Pitt-Hopkins syndrome). These disorders can be identified clinically by phenotyping across multiple neurodevelopmental and neurobehavioral realms, and enough data are available to recognize these postnatal microcephaly disorders as separate diagnostic entities in their own right. A second diagnostic grouping, comprised of Warburg MICRO syndrome, Cockayne syndrome, and Cerebral-oculo-facial skeletal syndrome, share similar features of somatic growth failure, ophthalmologic, and dysmorphologic features. Many postnatal microcephaly syndromes are caused by mutations in genes important in the regulation of gene expression in the developing forebrain and hindbrain, although important synaptic structural genes also play a role. This is an emerging group of disorders with a fascinating combination of brain malformations, specific epilepsies, movement disorders, and other complex neurobehavioral abnormalities.

Keywords: Angelman syndrome; CASK; CDKL5; Christianson syndrome; FOXG1; MECP2-related disorder; Pitt-Hopkins syndrome; Rubinstein-Taybi syndrome; Warburg MICRO syndrome, Cockayne syndrome, Cerebral-oculo-facial skeletal syndrome; postnatal microcephaly.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Angelman Syndrome / genetics*
  • Animals
  • Ataxia / genetics
  • Cataract / congenital*
  • Cataract / genetics
  • Cockayne Syndrome / genetics
  • Cornea / abnormalities*
  • Epilepsy / genetics
  • Facies
  • Genetic Diseases, X-Linked / genetics
  • Humans
  • Hyperventilation / genetics
  • Hypogonadism / genetics*
  • Intellectual Disability / genetics*
  • Microcephaly / genetics*
  • Mutation
  • Ocular Motility Disorders / genetics
  • Optic Atrophy / genetics*
  • Rett Syndrome / genetics*

Supplementary concepts

  • Mental Retardation, X-Linked, Syndromic, Christianson Type
  • Pitt-Hopkins syndrome
  • Warburg Sjo Fledelius syndrome