Severe manifestations of hand-foot-genital syndrome associated with a novel HOXA13 mutation

Am J Med Genet A. 2014 Sep;164A(9):2398-402. doi: 10.1002/ajmg.a.36648. Epub 2014 Jun 16.


We report on a girl with absent nails, short/absent distal phalanges of the second to fifth fingers and toes, short thumbs, absent halluces, and carpo-tarsal coalition who also had genitourinary malformations. Trio-based whole exome sequencing identified a novel de novo mutation (c.1102A>T, p.Ile368Phe) in the HOXA13 gene. Heterozygous HOXA13 mutations have been previously reported in hand-foot-genital syndrome and Guttmacher syndrome, which are variably associated with small nails, short distal and middle phalanges, short thumbs and halluces, but not absent nails. Considering the molecular data, the phenotype in the present patient was defined as the severe end of hand-foot-genital and Guttmacher syndrome spectrum. Our observation expands the clinical spectrum caused by heterozygous HOXA13 mutations and reinforces the difficulty of differential diagnosis on clinical grounds for the disorders with short distal phalanges, short thumbs, and short halluces.

Keywords: Guttmacher syndrome; HOXA13; genotype-phenotype correlation; hand-foot-genital syndrome.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / diagnostic imaging
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology*
  • Amino Acid Sequence
  • Base Sequence
  • Child
  • Female
  • Foot Deformities, Congenital / diagnostic imaging
  • Foot Deformities, Congenital / genetics*
  • Foot Deformities, Congenital / pathology*
  • Genetic Predisposition to Disease*
  • Hand Deformities, Congenital / diagnostic imaging
  • Hand Deformities, Congenital / genetics*
  • Hand Deformities, Congenital / pathology*
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Molecular Sequence Data
  • Mutation / genetics*
  • Radiography
  • Urogenital Abnormalities / diagnostic imaging
  • Urogenital Abnormalities / genetics*
  • Urogenital Abnormalities / pathology*


  • Homeodomain Proteins
  • homeobox protein HOXA13

Supplementary concepts

  • Hand foot uterus syndrome