Congenital Adrenal Hyperplasia
Congenital Adrenal Hyperplasia (CAH) is a group of diseases that are associated with variants or mutations in the genes that are involved in hormone production.
Overview
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Congenital Adrenal Hyperplasia (CAH) is a group of diseases that are associated with variants or mutations in the genes that are involved in hormone production. Specifically, CAH occurs when there is an excess of hormones in the adrenal gland.
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The classical form presents with prenatal onset of virilization caused by enzyme deficiency. Additionally, there is an imbalance of body hormones which could have severe effects throughout and individual’s lifetime including problems with fertility, obesity and hypertension.
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The nature of the genetic variants and genes associated with CAH means that testing for the condition is not straight forward. CAH can be tested for in three ways – CYP21A2 gene sequencing, CYP21A2 del/dup by MLPA and a gene panel associated with CAH not including the CYP21A2 gene. This condition is associated with recessive inheritance and is usually diagnosed at birth.
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The Igenomix Congenital Adrenal Hyperplasia Precision Panel can be used to make a directed and accurate differential diagnosis of ambiguous genitalia ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of treatment with a multidisciplinary team for pharmacologic treatment of lacking hormones, corrective surgery, specialist referral and dietary modifications.
- Risk assessment of asymptomatic family members according to the mode of inheritance.
Genes & Diseases
| GENE | OMIM DISEASES | INHERITANCE* | % GENE COVERAGE (20X) | HGMD** |
| ARMC5 | ACTH-Independent Macronodular Adrenal Hyperplasia, Cushing Syndrome Due To Macronodular Adrenal Hyperplasia | AD | 99.97% | 52 of 53 |
| CYP11A1 | 46,XY Disorder Of Sex Development-Adrenal Insufficiency Due To Cyp11A1 Deficiency, Congenital Adrenal Insufficiency | 100% | 39 of 39 | |
| CYP11B1 | Congenital Adrenal Hyperplasia Due To Steroid 11-Beta-Hydroxylase Deficiency,Familial Hyperaldosteronism Type I, Glucocorticoid-Remediable Aldosteronism | AD,AR | 100% | 144 of 144 |
| CYP11B2 | Corticosterone Methyloxidase Type I Deficiency, Corticosterone Methyloxidase Type II Deficiency, Familial Hyperaldosteronism Type I, Familial Hypoaldosteronism | AR | 100% | 42 of 42 |
| CYP17A1 | 46,XY Disorder Of Sex Development Due To Isolated 17,20-Lyase Deficiency, Congenital Adrenal Hyperplasia Due To 17-Alpha-Hydroxylase Deficiency | AR | 100% | 127 of 127 |
| CYP21A2 | Congenital Adrenal Hyperplasia Due To 21-Hydroxylase Deficiency | AR | 99.98% | 278 of 280 |
| HSD3B2 | Congenital Adrenal Hyperplasia Due To 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency, Congenital Adrenal Hyperplasia Due To 3-Beta-Hydroxysteroid Dehydrogenase Deficiency | AR | 100% | 70 of 70 |
| PDE11A | Pigmented Nodular Adrenocortical Disease, Primary Pigmented Nodular Adrenocortical Disease | AD | 99.98% | 17 of 17 |
| PDE8B | Autosomal Dominant Striatal Neurodegeneration, Pigmented Nodular Adrenocortical Disease, Primary Pigmented Nodular Adrenocortical Disease | AD | 99.98% | 10 of 10 |
| POR | Antley-Bixler Syndrome With Genital Anomalies And Disordered Steroidogenesis, Congenital Adrenal Hyperplasia Due To Cytochrome P450 Oxidoreductase Deficiency, Disordered Steroidogenesis Due To Cytochrome P450 Oxidoreductase | AD,AR | 99.98% | 67 of 68 |
| PRKAR1A | Acrodysostosis, Acute Promyelocytic Leukemia, Carney Complex, Familial Atrial Myxoma, Pigmented Nodular Adrenocortical Disease, Primary Pigmented Nodular Adrenocortical Disease | AD | 95.93% | 165 of 171 |
| STAR | Familial Glucocorticoid Deficiency, Lipoid Congenital Adrenal Hyperplasia | AR | 100% | 80 of 80 |
*Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial.
**Number of clinically relevant mutations according to HGMD
References
Narasimhan, M. L., & Khattab, A. (2019). Genetics of congenital adrenal hyperplasia and genotype-phenotype correlation. Fertility and sterility, 111(1), 24–29. https://doi.org/10.1016/j.fertnstert.2018.11.007
El-Maouche, D., Arlt, W., & Merke, D. P. (2017). Congenital adrenal hyperplasia. Lancet (London, England), 390(10108), 2194–2210. https://doi.org/10.1016/S0140-6736(17)31431-9
Merke, D. (2008). Approach to the Adult with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. The Journal Of Clinical Endocrinology & Metabolism, 93(3), 653-660. doi: 10.1210/jc.2007-2417
Hannah-Shmouni, F., Chen, W., & Merke, D. P. (2017). Genetics of Congenital Adrenal Hyperplasia. Endocrinology and metabolism clinics of North America, 46(2), 435–458. https://doi.org/10.1016/j.ecl.2017.01.008
Stratakis, C. A., & Rennert, O. M. (1999). Congenital adrenal hyperplasia: molecular genetics and alternative approaches to treatment. Critical reviews in clinical laboratory sciences, 36(4), 329–363. https://doi.org/10.1080/10408369991239222
