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J Med Ultrasound
J Med Ultrasound
JMU
J Med Ultrasound
Journal of Medical Ultrasound
0929-6441
2212-1552
Wolters Kluwer - Medknow India

JMU-32-271
10.4103/jmu.jmu_147_23
Research Letter
Early Prenatal Detection of Recessive Split-hand/Foot Malformation Caused by a Homozygous Variant of WNT10B
Chen Gui-Lan
Zhen Li
Li Dong-Zhi *
Prenatal Diagnostic Center, Guangzhou Women and Children’s Medical Center Affiliated to Guangzhou Medical University, Guangzhou, Guangdong, China
Address for correspondence: Dr. Dong-Zhi Li, Prenatal Diagnostic Center, Guangzhou Women and Children’s Medical Center affiliated to Guangzhou Medical University, Guangzhou, Guangdong, China. E-mail: drlidongzhi2014@sina.com
Jul-Sep 2024
28 8 2024
32 3 271272
14 11 2023
28 12 2023
11 1 2024
Copyright: © 2024 Journal of Medical Ultrasound
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
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pmcDear Editor,

Split-hand/foot malformation (SHFM) is a malformation of the limb involving the central rays of the autopod. It can occur as a single entity or as a part of the syndrome. SHFM is mainly inherited as an autosomal dominant trait with incomplete penetrance, involving different genetic variants.[1] The recessive SHFM has also been described.[2] We report a nonsyndromic fetal case of SHFM due to a homozygous WNT10B variant, which was diagnosed by ultrasound in the first trimester.

A 31-year-old Chinese woman, gravida 2 para 1, came for a routine first-trimester scan at 13 weeks of gestation. Both partners were healthy, in particular, did not show any hand or foot malformation, and their teeth examinations were normal. Both had a nonsignificant family history. They had a healthy 6-year-old daughter. The first-trimester scan identified a nuchal translucency (NT) of 2.0 mm with a crown-rump length of 70 mm. Notably, split defects were seen in both feet, with more severe in the left foot than in the right foot [Figure 1]. Further detailed examination showed a normal appearance of the head, face, heart, stomach, bladder, and hands. Pregnancy termination was required by the parents. Postnatal examination confirmed the prenatal findings. Trio-exome sequencing detected a causative WNT10B (NM_003394.4) variant, homozygous nonsense c. 786G>A, p.(Trp262*) in the fetus. Both parents were carriers for this variant which was classified as likely pathogenic according to the American College of Medical Genetics and Genomics guidelines.

Figure 1 Prenatal sonographic findings in the first trimester and sequence variations of WNT10B in family members. (a) Split defect in both feet, with more severe in the left foot, (b) normal morphology of both hands, (c) chromatograms of the WNT10B variant (c.786G > A), showing the homozygous state in the fetus, heterozygous state in the parents, and free from this variant in the daughter

Autosomal recessive SHFM (Type 6) is caused by WNT10B pathogenic variants.[2] The Trp262* variant in a heterozygous state was first reported in a sporadic Chinese patient with oligodontia as the cause of tooth agenesis.[3] However, no information was available for the dental conditions of that patient’s family members. In the present study, oligodontia was not identified in any family members who carried this variant. Therefore, the Trp262* might be an incidental finding in that study.[4]

Interestingly, only the foot was affected in our case. Indeed, one characteristic of SHFM caused by WNT10B variants is that the feet were more severely affected than the hands.[5] This characteristic is usually reflected in a WNT10B-related SHFM family, in which some siblings have mildly affected hands while all members have relatively severe foot defects. Traditionally, ectrodactyly was detected by sonography in mid-pregnancy. The fingers and feet can be visualized on ultrasound as soon as the long bones begin to ossify at 12 weeks gestation. Therefore, the hands and feet can potentially be visualized late in the first trimester, which is also an ideal time as the fetus has enough room to move for the limbs, and the hands are often open. Accordingly, the diagnosis of a split hand/foot is possibly achieved during the first trimester of pregnancy.[6]

In summary, we first reported the prenatal identification of recessive SHFM at the time of NT measurement. An early diagnosis has allowed the couple to make an informed decision in a timely manner before a viable fetus. Molecular investigation of such defects will be helpful in assessing the recurrent risk for future pregnancies and guide prevention.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that her names and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.
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