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.
Singh et al. (Fri,) studied this question.
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