Details of Disease

General Information of Disease (ID: DISMTRY0)

• Disease Name: Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency
• Synonyms: 21 hydroxylase deficiency; CYP21 deficiency; congenital adrenal hyperplasia due to 21-hydroxylase deficiency; adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency; adrenal hyperplasia 3; hyperandrogenism, Nonclassic type, due to 21-Hydroxylase deficiency; 21-hydroxylase deficiency; adrenal hyperplasia, congenital, due to 21-HYDROXYLASE deficiency; congenital adrenal hyperplasia 1; 21-OHD; classic 21-OHD CAH; classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency
• Definition: The most common form of congenital adrenal hyperplasia (CAH), characterized by simple virilizing or salt wasting forms that can manifest with genital ambiguity in females and with adrenal insufficiency (in both sexes), and that presents with dehydration, hypoglycemia in the neonatal period (that can be lethal if untreated), and hyperandrogenia.
• Disease Hierarchy:
  DIS7W23Z: Reproductive system disorder
  DISG873W: Congenital adrenal hyperplasia
  DISMTRY0: Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency
• Disease Identifiers:
  MONDO ID: MONDO_0008728
  MESH ID: C535979
  UMLS CUI: C2936858
  OMIM ID: 201910
  MedGen ID: 424833
  Orphanet ID: 90794

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GLO1	TTV9A7R	Limited	Genetic Variation	[1]
CYP11B1	TTIQUX7	Strong	Genetic Variation	[2]
CYP2B6	TTMH124	Strong	Genetic Variation	[3]
HSD17B1	TTIWB6L	Strong	Genetic Variation	[4]
IDS	TTNY2AP	Strong	Biomarker	[5]

This Disease Is Related to 4 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
HSD3B2	DEN0GVQ	Limited	Biomarker	[6]
CYP3A7	DERD86B	Strong	Biomarker	[7]
HSD3B1	DERDQWN	Strong	Altered Expression	[8]
CYP21A2	DE0JMZ5	Definitive	Autosomal recessive	[9]

This Disease Is Related to 5 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
C4A	OTXMOYXU	moderate	Genetic Variation	[10]
CAPN10	OTS9LJW4	Strong	Genetic Variation	[11]
CFC1	OT5DHGI8	Strong	Biomarker	[12]
GRB7	OTF8Y9XY	Strong	Genetic Variation	[13]
CYP21A2	OTN0UDVP	Definitive	Autosomal recessive	[9]

References

• [1] Extended MHC haplotypes in 21-hydroxylase-deficiency congenital adrenal hyperplasia: shared genotypes in unrelated patients.Lancet. 1983 Jan 22;1(8317):152-6. doi: 10.1016/s0140-6736(83)92757-5.
• [2] Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: functional consequences of four CYP11B1 mutations.Eur J Hum Genet. 2014 May;22(5):610-6. doi: 10.1038/ejhg.2013.197. Epub 2013 Sep 11.
• [3] Extraadrenal 21-hydroxylation by CYP2C19 and CYP3A4: effect on 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2009 Jan;94(1):89-95. doi: 10.1210/jc.2008-1174. Epub 2008 Oct 28.
• [4] A Single Nucleotide Variant in the Promoter Region of 17-HSD Type 5 Gene Influences External Genitalia Virilization in Females with 21-Hydroxylase Deficiency.Horm Res Paediatr. 2016;85(5):333-8. doi: 10.1159/000445684. Epub 2016 Apr 16.
• [5] Autopsy diagnosis of 21-hydroxylase deficiency CAH in a case of apparent SIDS.Pediatr Dev Pathol. 2005 May-Jun;8(3):397-401. doi: 10.1007/s10024-005-0004-0. Epub 2005 Jul 14.
• [6] Severe Salt-Losing 3-Hydroxysteroid Dehydrogenase Deficiency: Treatment and Outcomes of HSD3B2 c.35G>A Homozygotes.J Clin Endocrinol Metab. 2015 Aug;100(8):E1105-15. doi: 10.1210/jc.2015-2098. Epub 2015 Jun 16.
• [7] The effect of fetal androgen metabolism-related gene variants on external genitalia virilization in congenital adrenal hyperplasia.Clin Genet. 2013 Nov;84(5):482-8. doi: 10.1111/cge.12016. Epub 2012 Oct 8.
• [8] A case of 3beta-hydroxysteroid dehydrogenase type II (HSD3B2) deficiency picked up by neonatal screening for 21-hydroxylase deficiency: difficulties and delay in etiologic diagnosis.Horm Res. 2007;68(4):204-8. doi: 10.1159/000102593. Epub 2007 May 10.
• [9] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [10] The immunological detection of a 21-OH deficiency mutation HLA supratype.Am J Hum Genet. 1986 May;38(5):688-98.
• [11] Monogenic and polygenic models detected in steroid 21-hydroxylase deficiency-related paediatric hyperandrogenism.Horm Res. 2009 Jan;71(1):28-37. doi: 10.1159/000173739. Epub 2008 Nov 27.
• [12] Genetic and hormonal characterization of cryptic 21-hydroxylase deficiency.J Clin Endocrinol Metab. 1981 Dec;53(6):1193-8. doi: 10.1210/jcem-53-6-1193.
• [13] The HLA-A3, Cw6,B47,DR7 extended haplotypes in salt losing 21-hydroxylase deficiency and in the Old Order Amish: identical class I antigens and class II alleles with at least two crossover sites in the class III region.Tissue Antigens. 1995 Sep;46(3 ( Pt 1)):163-72. doi: 10.1111/j.1399-0039.1995.tb03115.x.