IMAGe and Related Undergrowth Syndromes: The Complex Spectrum of Gain-of-Function CDKN1C Mutations

Pediatr Endocrinol Rev. 2017 Mar;14(3):289-297. doi: 10.17458/per.vol14.2017.SKHD.imageandrelatedundergrowth.

Abstract

CDKN1C is a cyclin-dependent kinase Inhibitor and negative regulator of cellular proliferation. Recently, gain-of-function mutations in the PCNA domain of CDKN1C have been reported as the genetic basis of various growth-retarded syndromes including IMAGe syndrome, Russell Silver syndrome as well as a novel undergrowth syndrome that additionally exhibited early adulthood onset diabetes. This review summarizes the key clinical features and the molecular advances that have contributed to our understanding of this complex phenotypic spectrum.

Keywords: Adrenal hypoplasia; CDKN1C; IMAGe syndrome; Intrauterine growth restriction.

Publication types

  • Review

MeSH terms

  • Adrenal Insufficiency / classification
  • Adrenal Insufficiency / genetics*
  • Adrenal Insufficiency / pathology*
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics*
  • Fetal Growth Retardation / classification
  • Fetal Growth Retardation / genetics*
  • Fetal Growth Retardation / pathology*
  • Growth Disorders / genetics*
  • Humans
  • Male
  • Mutation
  • Osteochondrodysplasias / classification
  • Osteochondrodysplasias / genetics*
  • Osteochondrodysplasias / pathology*
  • Phenotype
  • Syndrome
  • Urogenital Abnormalities / classification
  • Urogenital Abnormalities / genetics*
  • Urogenital Abnormalities / pathology*

Substances

  • CDKN1C protein, human
  • Cyclin-Dependent Kinase Inhibitor p57

Supplementary concepts

  • Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, And Genital Anomalies