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DOI: 10.1055/s-0045-1814130
Uncovering the Genetic Basis of Recurrent Split Hand/Foot Malformation: A Case Report and Review
Authors
Abstract
Split hand/foot malformation (SHFM) is a clinically and genetically heterogeneous condition, characterized by variable severity due to reduced penetrance and variable expressivity. We report a family in which the husband and several other family members exhibited non-syndromic SHFM. The couple experienced three pregnancies affected by severe SHFM, leading to pregnancy terminations. An autopsy performed on one of the fetuses revealed features consistent with isolated SHFM. Whole exome sequencing of the husband did not identify any pathogenic variants. However, chromosomal microarray analysis revealed a 481-kb likely pathogenic duplication of the 10q24.31q24.32 region on chromosome 10, associated with SHFM type 3. While SHFM can be detected on ultrasound, genetic evaluation is essential for families with a history of this condition and a high risk of recurrence. This evaluation is particularly beneficial if the couple opts for in vitro fertilization with preimplantation genetic testing to avoid multiple pregnancy terminations.
Publication History
Article published online:
12 December 2025
© 2025. Society of Fetal Medicine. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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