Overlap of PIV syndrome, VACTERL and Pallister-Hall syndrome: clinical and molecular analysis

Clin Genet. 2000 Jul;58(1):28-30. doi: 10.1034/j.1399-0004.2000.580105.x.

Abstract

The polydactyly, imperforate anus, vertebral anomalies syndrome (PIV, OMIM 174100) was determined as a distinct syndrome by Say and Gerald in 1968 (Say B, Gerald PS. Lancet 1968: 2: 688). We noted that the features of PIV overlap with the VATER association and Pallister-Hall syndrome (PHS, OMIM 146510), which includes polydactyly, (central or postaxial), shortened fingers, hypoplastic nails, renal anomalies, imperforate anus, and hypothalamic hamartoma. Truncation mutations in GL13, a zinc finger transcription factor gene, have been shown to cause PHS. We performed a molecular evaluation on a patient diagnosed with PIV, whose mother, grandfather, and maternal aunt had similar malformations. We sequenced the GLI3 gene in the patient to determine if she had a mutation. The patient was found to have a deletion in nucleotides 2188-2207 causing a frameshift mutation that predicts a truncated protein product of the gene. Later clinical studies demonstrated that the patient also has a hypothalamic hamartoma, a finding in PHS. We concluded that this family had atypical PHS and not PIV. This result has prompted us to re-evaluate the PIV literature to see if PIV is a valid entity. Based on these data and our examination of the literature, we conclude that PIV is not a valid diagnostic entity. We conclude that patients diagnosed with PIV should be reclassified as having VACTERL, or PHS, or another syndrome with overlapping malformations.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Anus, Imperforate / genetics*
  • Base Sequence
  • DNA / blood
  • DNA-Binding Proteins / genetics
  • Exons
  • Female
  • Frameshift Mutation
  • Humans
  • Infant, Newborn
  • Introns
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins / genetics
  • Pedigree
  • Polydactyly / genetics*
  • Polymerase Chain Reaction
  • Repressor Proteins*
  • Sequence Analysis, DNA
  • Sequence Deletion
  • Spine / abnormalities*
  • Syndrome
  • Transcription Factors / genetics
  • Xenopus Proteins*
  • Zinc Finger Protein Gli3

Substances

  • DNA-Binding Proteins
  • GLI3 protein, Xenopus
  • GLI3 protein, human
  • Gli3 protein, mouse
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • Repressor Proteins
  • Transcription Factors
  • Xenopus Proteins
  • Zinc Finger Protein Gli3
  • DNA