Last reviewed 01/2018

Genetic factors leading to congenital limb anomalies

The advent of genome-wide screening has facilitated the discovery of a variety of genes that may be implicated or causal in the development of congenital limb anomalies. Analysis of genes in more primitive organisms such as the fruit fly has facilitated the discovery of analogous pathways in human limb development.

The genetic defect can be classified according to the protein molecule that is deranged:

• transcription factors:
  • Saethre-Chotzen Syndrome: TWIST gene located on chromosome 7p21
  • Holt-Oram Syndrome: TBX5 gene on chromosome 12q24.1
  • synpolydactyly: HOXD13 gene on choromosome 2q31-q32
  • Waardenburg's Syndrome type 1 and 3: PAX3 gene on chromosome 2q35
  • hand-foot-genital syndrome: HOXA13 gene on chromosome 7p15-p14.2
• signaling protein:
  • Hunter-Thompson Syndrome: CDMP1 gene on chromosome 20q11.2
  • Aarskog Syndrome: FGD1 gene on chromosome Xp11.2
• receptor proteins:
  • Apert's Syndrome: FGFR2 gene on chromosome 10q26
  • Pfeiffer's Syndrome: FGFR1 and FGFR2 genes on chromosomes 8p11.2-p11.1
  • Jackson-Weiss Syndrome: FGFR2 gene on chromosome 10q26
• indeterminate:
  • Nager's Syndrome: chromosome allele 9q32