Split hand/foot malformation associated with 20p12.1 deletion: A case report

Lyse Ruaud, Ricarda Flöttmann, Malte Spielmann, Fabienne Escande, Lionel Van Maldergem, Stefan Mundlos, Juliette Piard*

*Corresponding author for this work


Split hand/foot malformation (SHFM) or ectrodactyly is a rare congenital disorder affecting limb development characterized by clinical and genetic heterogeneity. SHFM is usually inherited as an autosomal dominant trait with incomplete penetrance. Isolated and syndromic forms are described. The extent of associated malformations is highly variable and multiple syndromes with clinical and genetic overlap have been described. We report here a 28 year-old man presenting with SHFM, sparse hair and widespread freckles. Array-CGH identified a 450 kb de novo 20p12.1 microdeletion encompassing three exons (exon 6 to 8) of MACROD2. Although MACROD2 mutations have not been associated with limb malformation until now, it is located next to KIF16B, which is involved in fibroblast growth factor receptor (FGFR) signaling. Additionally, the deletion encompassed a histone modification H3K27ac mark, known as a provider of quantitative readout of promoter and enhancer activity during human limb development. Altogether, these findings suggest that the 20p12.1 CNV is causative of SHFM in the present case through disturbance of regulatory elements functioning.

Original languageEnglish
Article number103805
JournalEuropean Journal of Medical Genetics
Issue number4
Pages (from-to)103805
Publication statusPublished - 04.2020

Research Areas and Centers

  • Centers: Center for Rare Diseases (ZSE)
  • Research Area: Medical Genetics

DFG Research Classification Scheme

  • 205-03 Human Genetics


Dive into the research topics of 'Split hand/foot malformation associated with 20p12.1 deletion: A case report'. Together they form a unique fingerprint.

Cite this