De novo SHANK3 mutation causes Rett syndrome-like phenotype in a female patient

Am J Med Genet A. 2015 Jul;167(7):1593-6. doi: 10.1002/ajmg.a.36775. Epub 2015 Apr 30.


Rett syndrome (RTT) is a neurodevelopmental disorder predominantly affecting females. Females with the MECP2 mutations exhibit a broad spectrum of clinical manifestations ranging from classical Rett syndrome to asymptomatic carriers. Mutations of genes encoding cyclin-dependent kinase-like 5 (CDKL5) and forkhead box G1 (FOXG1) are also found in early onset RTT variants. Here, we present the first report of a female patient with RTT-like phenotype caused by SHANK3 (SH3 and multiple ankylin repeat domain 3) mutation, indicating that the clinical spectrum of SHANK3 mutations may extend to RTT-like phenotype in addition to (severe) developmental delay, absence of expressive speech, autistic behaviors and intellectual disability.

Keywords: Rett syndrome; SHANK3; de novo; deletion; frameshift; whole-exome sequencing.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Exome / genetics
  • Female
  • Humans
  • Molecular Sequence Data
  • Multiplex Polymerase Chain Reaction
  • Nerve Tissue Proteins / genetics*
  • Phenotype*
  • Rett Syndrome / genetics*
  • Rett Syndrome / pathology*
  • Sequence Analysis, DNA


  • Nerve Tissue Proteins
  • SHANK3 protein, human

Supplementary concepts

  • Rett Syndrome, Atypical