Recurrence of split hand/foot malformation, cleft lip/palate, and severe urogenital abnormalities due to germline mosaicism for TP63 mutation

Am J Med Genet A. 2016 Sep;170(9):2372-6. doi: 10.1002/ajmg.a.37816. Epub 2016 Jun 28.

Abstract

We describe two sibling fetuses with urogenital abnormalities detected by prenatal ultrasound, in which post-delivery examination showed split hand and foot malformation, and bilateral cleft lip and palate. These findings are consistent with ectrodactyly-ectodermal dysplasia-cleft lip with or without cleft palate syndrome (EEC). Both fetuses were found to have the same missense mutation in TP63 (c.1051G > A; p.D351N). Parental clinical examinations and lymphocyte DNA analyses were normal. This report illustrates the potential severity of urogenital defects in TP63-related disorders, which may be detectable with fetal ultrasonography. It highlights the need to counsel for the possibility of germline mosaicism in TP63-associated disorders. © 2016 Wiley Periodicals, Inc.

Keywords: TP63; cleft lip; cleft palate; congenital limb deformities; ectodermal dysplasia; germline mosaicism; split hand/foot malformation; urogenital abnormalities.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Abortion, Induced
  • Adult
  • Child, Preschool
  • Cleft Lip / diagnosis
  • Cleft Lip / genetics*
  • Cleft Palate / diagnosis
  • Cleft Palate / genetics*
  • Comparative Genomic Hybridization
  • Female
  • Genetic Association Studies
  • Germ-Line Mutation*
  • Humans
  • Limb Deformities, Congenital / diagnosis
  • Limb Deformities, Congenital / genetics*
  • Male
  • Mosaicism*
  • Phenotype
  • Sequence Analysis, DNA
  • Syndrome
  • Transcription Factors / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Ultrasonography, Prenatal
  • Urogenital Abnormalities / diagnosis
  • Urogenital Abnormalities / genetics*

Substances

  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins

Supplementary concepts

  • Split hand foot deformity