Natural history of X-linked hypohidrotic ectodermal dysplasia: a 5-year follow-up study
Abstract Background X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by pathogenic variants of the gene EDA disrupting the prenatal development of ectodermal derivatives. Cardinal symptoms are hypotrichosis, lack of teeth, and hypo- or anhidrosis, but the disease may also evoke other cli...
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| Format: | Article |
| Language: | English |
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BMC
2020-01-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-019-1288-x |
| _version_ | 1828891549254025216 |
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| author | Sigrun Wohlfart Ralph Meiller Johanna Hammersen Jung Park Johannes Menzel-Severing Volker O. Melichar Kenneth Huttner Ramsey Johnson Florence Porte Holm Schneider |
| author_facet | Sigrun Wohlfart Ralph Meiller Johanna Hammersen Jung Park Johannes Menzel-Severing Volker O. Melichar Kenneth Huttner Ramsey Johnson Florence Porte Holm Schneider |
| author_sort | Sigrun Wohlfart |
| collection | DOAJ |
| description | Abstract Background X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by pathogenic variants of the gene EDA disrupting the prenatal development of ectodermal derivatives. Cardinal symptoms are hypotrichosis, lack of teeth, and hypo- or anhidrosis, but the disease may also evoke other clinical problems. This study aimed at investigating the clinical course of XLHED in early childhood as the basis for an evaluation of the efficacy of potential treatments. Methods 25 children (19 boys and 6 girls between 11 and 35 months of age) with genetically confirmed XLHED were enrolled in a long-term natural history study. Clinical data were collected both retrospectively using parent questionnaires and medical records (pregnancy, birth, infancy) and prospectively until the age of 60 months. General development, dentition, sweating ability, ocular, respiratory, and skin involvement were assessed by standardized clinical examination and yearly quantitative surveys. Results All male subjects suffered from persistent anhidrosis and heat intolerance, although a few sweat ducts were detected in some patients. Sweating ability of girls with XLHED ranged from strongly reduced to almost normal. In the male subjects, 1–12 deciduous teeth erupted and 0–8 tooth germs of the permanent dentition became detectable. Tooth numbers were higher but variable in the female group. Most affected boys had no more than three if any Meibomian glands per eyelid, most girls had fewer than 10. Many male subjects developed additional, sometimes severe health issues, such as obstructive airway conditions, chronic eczema, or dry eye disease. Adverse events included various XLHED-related infections, unexplained fever, allergic reactions, and retardation of psychomotor development. Conclusions This first comprehensive study of the course of XLHED confirmed the early involvement of multiple organs, pointing to the need of early therapeutic intervention. |
| first_indexed | 2024-12-13T13:18:55Z |
| format | Article |
| id | doaj.art-0150e33520264ab79bca69a84cac4ccc |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-13T13:18:55Z |
| publishDate | 2020-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-0150e33520264ab79bca69a84cac4ccc2022-12-21T23:44:26ZengBMCOrphanet Journal of Rare Diseases1750-11722020-01-0115111110.1186/s13023-019-1288-xNatural history of X-linked hypohidrotic ectodermal dysplasia: a 5-year follow-up studySigrun Wohlfart0Ralph Meiller1Johanna Hammersen2Jung Park3Johannes Menzel-Severing4Volker O. Melichar5Kenneth Huttner6Ramsey Johnson7Florence Porte8Holm Schneider9Center for Ectodermal Dysplasias & Department of Pediatrics, University Hospital ErlangenDepartment of Ophthalmology, University of Erlangen-NürnbergCenter for Ectodermal Dysplasias & Department of Pediatrics, University Hospital ErlangenCenter for Ectodermal Dysplasias & Department of Pediatrics, University Hospital ErlangenDepartment of Ophthalmology, University of DüsseldorfCenter for Ectodermal Dysplasias & Department of Pediatrics, University Hospital ErlangenEdimer PharmaceuticalsEdimer PharmaceuticalsEspeRare FoundationCenter for Ectodermal Dysplasias & Department of Pediatrics, University Hospital ErlangenAbstract Background X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by pathogenic variants of the gene EDA disrupting the prenatal development of ectodermal derivatives. Cardinal symptoms are hypotrichosis, lack of teeth, and hypo- or anhidrosis, but the disease may also evoke other clinical problems. This study aimed at investigating the clinical course of XLHED in early childhood as the basis for an evaluation of the efficacy of potential treatments. Methods 25 children (19 boys and 6 girls between 11 and 35 months of age) with genetically confirmed XLHED were enrolled in a long-term natural history study. Clinical data were collected both retrospectively using parent questionnaires and medical records (pregnancy, birth, infancy) and prospectively until the age of 60 months. General development, dentition, sweating ability, ocular, respiratory, and skin involvement were assessed by standardized clinical examination and yearly quantitative surveys. Results All male subjects suffered from persistent anhidrosis and heat intolerance, although a few sweat ducts were detected in some patients. Sweating ability of girls with XLHED ranged from strongly reduced to almost normal. In the male subjects, 1–12 deciduous teeth erupted and 0–8 tooth germs of the permanent dentition became detectable. Tooth numbers were higher but variable in the female group. Most affected boys had no more than three if any Meibomian glands per eyelid, most girls had fewer than 10. Many male subjects developed additional, sometimes severe health issues, such as obstructive airway conditions, chronic eczema, or dry eye disease. Adverse events included various XLHED-related infections, unexplained fever, allergic reactions, and retardation of psychomotor development. Conclusions This first comprehensive study of the course of XLHED confirmed the early involvement of multiple organs, pointing to the need of early therapeutic intervention.https://doi.org/10.1186/s13023-019-1288-xHypohidrotic ectodermal dysplasiaNatural historyEctodysplasin AOligodontiaDry eyeHeat intolerance |
| spellingShingle | Sigrun Wohlfart Ralph Meiller Johanna Hammersen Jung Park Johannes Menzel-Severing Volker O. Melichar Kenneth Huttner Ramsey Johnson Florence Porte Holm Schneider Natural history of X-linked hypohidrotic ectodermal dysplasia: a 5-year follow-up study Orphanet Journal of Rare Diseases Hypohidrotic ectodermal dysplasia Natural history Ectodysplasin A Oligodontia Dry eye Heat intolerance |
| title | Natural history of X-linked hypohidrotic ectodermal dysplasia: a 5-year follow-up study |
| title_full | Natural history of X-linked hypohidrotic ectodermal dysplasia: a 5-year follow-up study |
| title_fullStr | Natural history of X-linked hypohidrotic ectodermal dysplasia: a 5-year follow-up study |
| title_full_unstemmed | Natural history of X-linked hypohidrotic ectodermal dysplasia: a 5-year follow-up study |
| title_short | Natural history of X-linked hypohidrotic ectodermal dysplasia: a 5-year follow-up study |
| title_sort | natural history of x linked hypohidrotic ectodermal dysplasia a 5 year follow up study |
| topic | Hypohidrotic ectodermal dysplasia Natural history Ectodysplasin A Oligodontia Dry eye Heat intolerance |
| url | https://doi.org/10.1186/s13023-019-1288-x |
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