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Congenital adrenal insufficiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency

MedGen UID:
462405
Concept ID:
C3151055
Disease or Syndrome
Synonyms: Adrenal insufficiency, congenital, with 46,XY sex reversal, partial or complete; Congenital adrenal insuffiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency; P450scc DEFICIENCY
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): CYP11A1 (15q24.1)
 
Monarch Initiative: MONDO:0013400
OMIM®: 613743
Orphanet: ORPHA168558

Definition

P450scc deficiency is a rare disorder that can present as acute adrenal insufficiency in infancy or childhood. ACTH and plasma renin activity are grossly elevated and adrenal steroids are inappropriately low or absent; the 46,XY patients have female external genitalia, sometimes with clitoromegaly. The phenotypic spectrum ranges from prematurity, complete underandrogenization, and severe early-onset adrenal failure to term birth with clitoromegaly and later-onset adrenal failure (summary by Kim et al., 2008). Although hormonal and phenotypic features can resemble those of congenital lipoid adrenal hyperplasia (lipoid CAH; 201710), no patient with P450scc deficiency has been described with the massive adrenal enlargement typical of lipoid CAH (summary by Sahakitrungruang et al., 2011). [from OMIM]

Clinical features

From HPO
Renal salt wasting
MedGen UID:
375868
Concept ID:
C1846347
Finding
A high concentration of one or more electrolytes in the urine in the presence of low serum concentrations of the electrolyte(s).
Sex reversal
MedGen UID:
868596
Concept ID:
C4022995
Finding
Development of the reproductive system is inconsistent with the chromosomal sex.
Adrenocorticotropic hormone excess
MedGen UID:
866773
Concept ID:
C4021124
Pathologic Function
Overproduction of adrenocorticotropic hormone (ACTH), which generally leads secondarily to overproduction of cortisol by the adrenal cortex.
Hyperpigmentation of the skin
MedGen UID:
57992
Concept ID:
C0162834
Pathologic Function
A darkening of the skin related to an increase in melanin production and deposition.
Adrenal insufficiency
MedGen UID:
1351
Concept ID:
C0001623
Disease or Syndrome
Insufficient production of steroid hormones (primarily cortisol) by the adrenal glands.
Increased circulating aldosterone concentration
MedGen UID:
6960
Concept ID:
C0020428
Disease or Syndrome
Overproduction of the mineralocorticoid aldosterone by the adrenal cortex.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCongenital adrenal insufficiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency
Follow this link to review classifications for Congenital adrenal insufficiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency in Orphanet.

Recent clinical studies

Etiology

Parajes S, Chan AO, But WM, Rose IT, Taylor AE, Dhir V, Arlt W, Krone N
Eur J Endocrinol 2012 Dec;167(6):881-5. Epub 2012 Sep 11 doi: 10.1530/EJE-12-0450. PMID: 22968487Free PMC Article
Idkowiak J, O'Riordan S, Reisch N, Malunowicz EM, Collins F, Kerstens MN, Köhler B, Graul-Neumann LM, Szarras-Czapnik M, Dattani M, Silink M, Shackleton CH, Maiter D, Krone N, Arlt W
J Clin Endocrinol Metab 2011 Mar;96(3):E453-62. Epub 2010 Dec 29 doi: 10.1210/jc.2010-1607. PMID: 21190981Free PMC Article

Diagnosis

Matusik P, Gach A, Zajdel-Cwynar O, Pinkier I, Kudela G, Gawlik A
Int J Environ Res Public Health 2021 Jul 5;18(13) doi: 10.3390/ijerph18137186. PMID: 34281122Free PMC Article
Kim A, Fujimoto M, Hwa V, Backeljauw P, Dauber A
Horm Res Paediatr 2018;89(3):205-210. Epub 2018 Mar 22 doi: 10.1159/000487638. PMID: 29566378Free PMC Article
Ravel C, Hyon C, Siffroi JP, Christin-Maitre S
Ann Endocrinol (Paris) 2014 May;75(2):126-7. Epub 2014 Apr 21 doi: 10.1016/j.ando.2014.03.003. PMID: 24751136
Idkowiak J, O'Riordan S, Reisch N, Malunowicz EM, Collins F, Kerstens MN, Köhler B, Graul-Neumann LM, Szarras-Czapnik M, Dattani M, Silink M, Shackleton CH, Maiter D, Krone N, Arlt W
J Clin Endocrinol Metab 2011 Mar;96(3):E453-62. Epub 2010 Dec 29 doi: 10.1210/jc.2010-1607. PMID: 21190981Free PMC Article
Smyk M, Berg JS, Pursley A, Curtis FK, Fernandez BA, Bien-Willner GA, Lupski JR, Cheung SW, Stankiewicz P
Hum Genet 2007 Aug;122(1):63-70. Epub 2007 May 15 doi: 10.1007/s00439-007-0373-8. PMID: 17503084

Therapy

Ravel C, Hyon C, Siffroi JP, Christin-Maitre S
Ann Endocrinol (Paris) 2014 May;75(2):126-7. Epub 2014 Apr 21 doi: 10.1016/j.ando.2014.03.003. PMID: 24751136
Yüksel B, Kulle AE, Gürbüz F, Welzel M, Kotan D, Mengen E, Holterhus PM, Topaloğlu AK, Grötzinger J, Riepe FG
Horm Res Paediatr 2013;80(3):163-9. Epub 2013 Aug 1 doi: 10.1159/000354086. PMID: 23920000
Idkowiak J, O'Riordan S, Reisch N, Malunowicz EM, Collins F, Kerstens MN, Köhler B, Graul-Neumann LM, Szarras-Czapnik M, Dattani M, Silink M, Shackleton CH, Maiter D, Krone N, Arlt W
J Clin Endocrinol Metab 2011 Mar;96(3):E453-62. Epub 2010 Dec 29 doi: 10.1210/jc.2010-1607. PMID: 21190981Free PMC Article

Clinical prediction guides

Joshi R, Das D, Tamhankar P, Shaikh S
Indian Pediatr 2014 May;51(5):399-400. PMID: 24953586

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