Genotype/phenotype correlations in 538 congenital adrenal hyperplasia patients from Germany and Austria: discordances in milder genotypes and in screened versus prescreening patients
Open accessAbstract
Congenital adrenal hyperplasia (CAH) due to CYP21A2 gene mutations is associated with a variety of clinical phenotypes (salt wasting, SW; simple virilizing, SV; nonclassical, NC) depending on residual 21-hydroxylase activity. Phenotypes and genotypes correlate well in 80-90% of cases. We set out to test the predictive value of CAH phenotype assignment based on genotype classification in a large multicenter cohort. A retrospective evaluation of genetic data from 538 CAH patients (195 screened) collected from 28 tertiary centers as part of a German quality control program was performed. Genotypes were classified according to residual 21-hydroxylase activity (null, A, B, C) and assigned clinical phenotypes correlated with predicted phenotypes, including analysis of Prader stages. Ultimately, concordance of genotypes with clinical phenotypes was compared in patients diagnosed before or after the introduction of nationwide CAH-newborn screening. Severe genotypes (null and A) correlated well with the expected phenotype (SW in 97 and 91%, respectively), whereas less severe genotypes (B and C) correlated poorly (SV in 45% and NC in 57%, respectively). This was underlined by a high degree of virilization in girls with C genotypes (Prader stage >1 in 28%). SW was diagnosed in 90% of screening-positive babies with classical CAH compared with 74% of prescreening patients. In our CAH series, assigned phenotypes were more severe than expected in milder genotypes and in screened vs prescreening patients. Diagnostic discrimination between phenotypes based on genotypes may prove overcome due to the overlap in their clinical presentations.
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Females outnumber males in some but not all retrospective studies in which CAH was clinically diagnosed without neonatal screening.
“Females do outnumber males in some(12,240,241) although not all (242) retrospective studies in which CAH was clinically diagnosed without neonatal screening.”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [241]
Citation (242) is attached to “not all,” offering this study as an example of a retrospectively studied, clinically diagnosed prescreening group without a female majority. The Results (Eligible patients; page unavailable) say the opposite: females made up 64% of the prescreening group. The approximately equal sex distribution was in the screened group, which does not fit that clause. (LLM, conf=0.88)
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Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management
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Self-citationCharacteristics of In2G Variant in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency
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- Authors
- Riedl, S., Röhl, F.-W., Bonfig, W., Brämswig, J., Richter-Unruh, A., Fricke-Otto, S., Bettendorf, M., Riepe, F., Kriegshäuser, G., Schönau, E., Even, G., Hauffa, B., Dörr, H.-G., Holl, R. W., Mohnike, K., & _, _.
- Affiliations
- St Anna Children's Hospital (AT)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Klinikum Wels-Grieskirchen (AT)
- University of Münster (DE)
- 6Department of Pediatrics, Pediatric Endocrinology, Helios Klinikum Krefeld, Krefeld, Germany
- Heidelberg University (DE)
- 8Pediatric Endocrinology, Kronshagen, Kiel, Germany
- 9Institute of Clinical Chemistry and Laboratory Medicine, General Hospital Steyr, Steyr, Austria
- 10Department of Pediatrics, Pediatric Endocrinology, Universität zu Köln, Cologne, Germany
- University of Cologne (DE)
- University of Duisburg-Essen (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Universität Ulm (DE)
- Corresponding author
- Riedl, Stefan
- ORCID
- Venue
- Endocrine Connections
- Publisher
- Bioscientifica
- Published
- 2019-02
- Volume
- 8
- Issue
- 2
- Pages
- 86-94
- ISSN
- 2049-3614 (ISSN-L)
- PMC
- PMC6365666
- OpenAlex
- W2910390930
- Cited by
- 69
- References
- 33
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 8 · 2023: 10 · 2022: 8 · 2021: 17 · 2020: 7 · 2019: 4
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Endocrine Connections (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- congenital adrenal hyperplasia, CYP21A2 mutations, genotype-phenotype correlation, newborn screening, salt wasting, simple virilizing CAH, genotype classification
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