Prenatal sonographic clues suggestive of hypohidrotic ectodermal dysplasia in a fetus: a case description

Introduction

Hypohidrotic ectodermal dysplasia (HED) is a potentially life-threatening genetic disorder with an estimated incidence of approximately 1 in 10,000 live births. It can affect all tissues derived from the embryonic ectoderm, leading to structural and functional abnormalities. The classic triad of clinical features includes sparse hair, hypodontia/anodontia, and hypohidrosis (1,2). HED is associated with genetic abnormalities (3), with common inheritance patterns including autosomal dominant, autosomal recessive, and X-linked recessive (the most frequent). The majority of affected individuals are male (1). Approximately 30% of patients may die due to hyperthermia and associated infections (2,4). Diagnosis primarily relies on molecular testing, which can be time-consuming, and some genotypes remain unidentified. Treatment is mainly supportive. Patients often experience significant psychological, social, and economic burdens due to masticatory dysfunction and distinctive facial features (5). Therefore, early identification is crucial for genetic counseling and prognosis. This article presents the sonographic features, family history, and postnatal findings in a fetus suggestive of HED, aiming to inform its prenatal diagnosis.

A 27-year-old pregnant woman (G2P0) underwent ultrasound examination at 23 weeks of gestation, which revealed fetal findings including a thin alveolar ridge, an abnormal number of tooth germs, a pointed inferior alveolar arch, slightly everted lips, and a prominent mandible (Figure 1). History investigation indicated non-consanguineous/ marriage and no exposure to known teratogens. In her previous pregnancy, amniocentesis was performed due to similar alveolar anomalies, which identified a heterozygous WNT10A gene mutation (c.511C>T), classified as a variant of uncertain significance. This mutation was determined to be maternal in origin (inherited from the patient’s mother). That pregnancy with a male fetus was terminated. Both the pregnant woman and her mother exhibited clinical features of sparse hair, hypohidrosis, and congenital absence of teeth. Her maternal uncle also presented with similar, but more severe, symptoms. Based on ultrasound and family history, HED was highly suspected. Amniocentesis was recommended but declined by the family, and the pregnancy continued. Late-trimester ultrasound showed no obvious fetal lanugo hair, and a male infant was vaginally delivered at 39 weeks. Follow-up to 3 years of age revealed anodontia, sparse eyebrows and scalp hair, hypohidrosis, dry skin, protruding ears, and mild hypertelorism (Figure 2), with normal intellectual development. The combination of family history, prenatal sonographic features, and postnatal clinical presentation was consistent with the prenatal diagnosis. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Gansu Provincial Maternity and Child Care Hospital (No. 2024GSFY07), and the requirement for individual consent for this retrospective analysis was waived. The study represents an independent analysis of a distinct patient cohort.

Figure 1 Ultrasonographic features of the case compared with a normal gestational-age-matched fetus. (A-D) Ultrasonographic features of the fetus in this case. (A,B) Transverse alveolar ridge views: absent hypoechoic tooth germs, thin/poorly ossified ridges, and a sharply tapered mandibular arch. (C) The midsagittal view revealed a tapered and slightly protrusive mandible. (D) The oblique oral commissure view showed mild lip eversion. (E-H) Compared with a normal gestational-age-matched fetus. (E,F) Well ossified alveolar ridges with hypoechoic tooth germs arranged in an arch. (G,H) Normal mandibular and lip morphology.

Figure 2 Postnatal clinical manifestations of the case. (A) Sparse hair and eyebrows, mildly everted lips, dry skin. (B) Dental aplasia. This image is published with the participant’s consent.

Discussion

Based on suspicion, the prenatal diagnosis of HED is challenging, with limited reports on its sonographic features. This article presents a case of a fetus with prenatal ultrasound findings of alveolar and tooth germ anomalies, along with a clear family history of HED. The postnatal clinical presentation was consistent with the disorder. This case suggests that detailed ultrasonographic assessment of the maxillofacial region may provide crucial clues suggestive of HED. In this case, features such as a thin alveolar ridge, a pointed inferior alveolar arch, an abnormal tooth germ count, everted lips, and a prominent mandible may represent characteristic sonographic signs of HED (2,3,6). The absence or sparseness of fetal lanugo hair in the late trimester may serve as a supportive finding. For individuals with a clear family history, detailed maxillofacial ultrasonography incorporating these assessments should be considered an essential component of prenatal evaluation.

Differential diagnoses should be considered when alveolar ridge or tooth germ abnormalities are detected prenatally. These include other ectodermal dysplasias [e.g., ectodysplasin A (EDA)-related HED, Rapp-Hodgkin syndrome], cleft palate variants with secondary alveolar changes, and isolated dental anomalies without systemic involvement. The presence of additional features such as sparse lanugo hair, everted lips, and a positive family history of hypohidrosis or tooth agenesis may help to distinguish HED from other conditions.

Previous reports on HED have primarily linked it to anomalies in the EDA gene (2,3,7). In addition, WNT10A has been reported to be associated with ectodermal dysplasia (8); the pathogenicity of this specific variant requires further validation through segregation analysis within the family or functional studies. It is also necessary to mention the potential diagnosis of ectodermal dysplasia in the mother, her brother, and her maternal mother, as well as the presence of the heterozygous WNT10A variant in all three affected individuals, in contrast to unaffected relatives who likely do not carry the same variant. Notably, as invasive prenatal diagnosis was not performed for the second fetus, the diagnosis of HED in this case remains a prenatal suspicion.

The highly consistent prenatal sonographic features and postnatal phenotype strongly suggest a familial inheritance pattern (1,8). Therefore, meticulous collection of family history and pedigree verification are crucial for interpreting both sonographic findings and genetic results. Although invasive prenatal diagnosis was not performed in this case, the highly concordant prenatal sonographic features and postnatal phenotype strongly indicate a familial inheritance pattern. Therefore, the meticulous collection of family history and pedigree verification are crucial for accurately interpreting both sonographic findings and genetic results.

Currently, no curative treatment is available for HED, and management is primarily supportive (7); key measures include the following: (I) avoiding hot environments and using air conditioning to prevent hyperthermia; (II) early dental intervention (orthodontics, implants) to restore masticatory function and improve aesthetics; and (III) nutritional support for children with chewing difficulties.

A limitation of this study is the absence of invasive prenatal diagnosis for the second fetus (declined by the pregnant woman and her family). Notably, to optimize clinical management, a standardized approach is essential. A detailed family history via a genetics expert is required to evaluate inheritance and recurrence risk. Besides, when ultrasound anomalies are found alongside a familial WNT10A variant, prenatal testing for the variant should be offered, enabling informed family decisions on pregnancy management and prenatal diagnosis.

Conclusions

Prenatal sonographic suspicion of HED demonstrates a certain degree of specificity. A thin alveolar ridge with reduced echogenicity, an abnormal tooth germ count, along with morphological changes of the lips and mandible, may serve as early sonographic clues raising suspicion for fetal HED. For pregnant women with a relevant family history, prenatal ultrasonographic assessment of the fetal maxillofacial region can serve as an effective screening tool. Genetic testing is recommended for suspected cases to confirm the etiology.

Acknowledgments

None.

Footnote

Funding: This work was supported by the Lanzhou City Science and Technology Plan Project (No. 2022-3-15) and the Gansu Provincial Natural Science Foundation (No. 22JR5RA726).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2026-1-0346/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Gansu Provincial Maternity and Child Care Hospital (No. 2024GSFY07). Written informed consent was obtained from the patient’s legal guardians for the publication of this study and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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