A prenatal case of split-hand malformation associated with 17p13.3 triplication - a dilemma in genetic counseling

Eur J Med Genet. 2014 Feb;57(2-3):81-4. doi: 10.1016/j.ejmg.2013.12.005. Epub 2013 Dec 28.


Copy number gain of 17p13.3 has been shown to be associated with developmental delay/autism and Split-Hand-Foot malformation. We report a case of fetus with bilateral split-hand malformation detected on prenatal ultrasound. Array comparative genomic hybridization detected 2 maternally inherited copy number gains in the 17p13.3 region with one of them involving the BHLHA9 gene and part of the YWHAE gene. The mother is normal in intelligence with mild right foot anomaly only. Although the BHLHA9 copy gain is known to be associated with split-hand-foot malformation, the penetrance and expressivity is highly variable. More challenging is the effect of partial YWHAE copy number gain on neurodevelopment is inconclusive based on current literature. This case highlights the difficulties of prenatal genetic counseling in array comparative genomic hybridization findings in clinical situation with incomplete understanding of genotype-phenotype correlation.

Keywords: 17p13.3 copy number gain; Autism; Developmental delay; Prenatal diagnosis; Split hand malformation.

Publication types

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

MeSH terms

  • Adult
  • Autopsy
  • Chromosomes, Human, Pair 17*
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations
  • Female
  • Genetic Counseling
  • Hand Deformities, Congenital / diagnosis
  • Hand Deformities, Congenital / genetics*
  • Humans
  • Phenotype
  • Pregnancy
  • Trisomy*
  • Ultrasonography, Prenatal