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Congenital adrenal hyperplasia caused by compound heterozygosity of two novel CYP11B1 gene variants

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Abstract

Background

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by pathogenic variants in seven genes involved in the cortisol and aldosterone biosynthetic pathway. The second most common cause, 11β-hydroxylase deficiency (11βOHD), is attributed to pathogenic variants in the CYP11B1 gene encoding for the enzyme 11β-hydroxylase (11βOH).

Case presentation

A 13-year-old girl was referred to the pediatric endocrinologist due to a syncopal episode. She is the third child of non-consanguineous parents. She presented with premature adrenarche at the age of 6 years and menarche at the age of 12 years. On physical examination, her height was 154.5 cm and weight 50 kg, while she presented with acne, hirsutism, clitoromegaly, and normal blood pressure. Laboratory investigation revealed increased androgen levels and poor cortisol response to the ACTH stimulation test. From the family history, the mother was diagnosed with CAH at the age of 10 years and was under treatment with methylprednisolone. Previous molecular investigation of the CYP21A2 gene was negative. Due to the increased androstenedione levels in the index patient, the suspicion of 11βOH was raised, and she was investigated for 11-deoxycortisol, 11-deoxycorticosterone, and CYP11B1 gene pathogenic variants. The patient and her mother were found to be compound heterozygous for two novel variants of the CYP11B1 gene.

Conclusion

We present a case of CAH due to compound heterozygosity of two novel pathogenic variants of the CYP11B1 gene, emphasizing the importance of molecular investigation in order to confirm clinical diagnosis and allow proper genetic counseling of the family.

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Acknowledgements

The authors would like to thank the family for participating in this study. The authors would also like to thank Mrs. Eleni Golfinopoulou for her expert technical assistance.

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Authors and Affiliations

  1. Division of Endocrinology, Diabetes and Metabolism, Center for Rare Paediatric Endocrine Diseases, First Department of Paediatrics, Medical School, National and Kapodistrian University of Athens, Agia Sophia” Children’s Hospital, Athens, Greece

    I. Fylaktou, P. Smyrnaki, A. Sertedaki, M. Dracopoulou & Ch. Kanaka-Gantenbein

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  1. I. Fylaktou
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  2. P. Smyrnaki
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  3. A. Sertedaki
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  4. M. Dracopoulou
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Contributions

I.F.: genetic analysis and writing of the manuscript. P.S: referred the patient and provided the clinical information. A.S.: genetic analysis, reviewing and editing of the manuscript. M.D.: design of the genetic study and genetic analysis. Ch.K.G: reviewing and editing of the manuscript.

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Correspondence to A. Sertedaki.

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Fylaktou, I., Smyrnaki, P., Sertedaki, A. et al. Congenital adrenal hyperplasia caused by compound heterozygosity of two novel CYP11B1 gene variants. Hormones 21, 155–161 (2022). https://doi.org/10.1007/s42000-021-00322-1

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