Adrenal Hypoplasia, Congenital

Alternative Names

  • AHC
  • Adrenal Hypoplasia, Congenital, with Hypogonadotropic Hypogonadism
  • AHCH
  • Addison Disease, X-Linked
  • AHX
  • AHC with HHG
  • Cytomegalic Adrenocortical Hypoplasia
  • AHC with Isolated Gonadotropin Deficiency
  • Adrenal Insufficiency, Progressive, and Hypogonadotropic Hypogonadism
  • Mineralocorticoid Deficiency, Isolated
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Other congenital malformations

OMIM Number

300200

Mode of Inheritance

X-linked recessive

Gene Map Locus

Xp21.2

Description

Congenital Adrenal Hypoplasia (AHC) is a genetic disorder that results from a number of causes, ranging from deficiency in functioning of the Adrenocorticotropic Hormone (ACTH) to defects in the ACTH receptor. Primary Congenital Adrenal Hypoplasia is caused due to defects in the development and differentiation of the adrenal cortex. Affected children present with vomiting, feeding difficulties, dehydration, failure to thrive, salt wasting, hypoglycemic convulsions, and hyperpigmentation in the first months of life. They show no response to ACTH stimulation, and plasma concentrations of mineralocorticoids and glucocorticoids are decreased. Some patients have undescended testes, and may have micropenis, hypospadias or cryptorchidism. Histologically, the adrenal glands lack the definitive zone of the adrenal cortex and are characterized by large vacuolated cells resembling fetal adrenocortical cells.

Diagnosis of AHC can be made based on the clinical signs. Abdominal CT can be useful for diagnosis, except in the case of infants, since the fetal adrenal zone is preserved in them. In infants, abdominal ultrasound may be more useful. Early diagnosis of the condition is essential for effective management. Initial management involves stabilizing salt and glucose levels. Patients are treated with glucocorticoids and mineralocorticoids, and should have enough sodium and fluids in their diet. Some patients may develop hypogonadotropic hypogonadism, while some may develop sensorineural hearing loss.

Molecular Genetics

Congenital Adrenal Hypoplasia can be transmitted in either an X-linked, autosomal recessive, or autosomal dominant fashion. The X-linked form of the condition is caused due to mutations in the DAX1 (DSS-AHC Critical Region on the X Chromosome 1) gene. The protein encoded by this gene belongs to the nuclear hormone receptor superfamily. However, the ligand for this receptor is unknown, making it an orphan receptor. The DAX1 protein acts as a co-regulatory protein that inhibits the transcriptional activity of other nuclear receptors. It also appears to function as an antitestis gene by acting antagonistically to the sex-determining region. However, the precise role of this protein in hypothalamic and adrenal cortical development remains unclear.

In some patients, the mutation involved is a large deletion in the X-chromosome involving the DAX1 gene and the contiguous gene loci for Duchenne Muscular Dystrophy, and Glycerol Kinase Deficiency.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
300200.1.1United Arab EmiratesMaleYesYes Congenital adrenal hypoplasia; Death in...NM_000475.4:c.1130A>GHomozygousAutosomal, RecessiveWalker et al. 2012
300200.1.2United Arab EmiratesMaleYesYes Congenital adrenal hypoplasiaNM_000475.4:c.1130A>GHomozygousAutosomal, RecessiveWalker et al. 2012 Brother of 300200.1....
300200.1.3United Arab EmiratesMaleYesYes Congenital adrenal hypoplasiaNM_000475.4:c.1130A>GHomozygousAutosomal, RecessiveWalker et al. 2012 First cousin of 3002...
300200.1.4United Arab EmiratesMaleYesYes Congenital adrenal hypoplasia; Death in...NM_000475.4:c.1130A>GHomozygousAutosomal, RecessiveWalker et al. 2012 Uncle of 300200.1.1
300200.1.5United Arab EmiratesMaleYesYes Congenital adrenal hypoplasia; Death in...NM_000475.4:c.1130A>GHomozygousAutosomal, RecessiveWalker et al. 2012 Uncle of 300200.1.1
300200.1.6United Arab EmiratesMaleYesYes Congenital adrenal hypoplasia; ;NM_000475.4:c.1130A>GHomozygousAutosomal, RecessiveWalker et al. 2012 First cousin, once r...
300200.1.7United Arab EmiratesMaleYesYes Congenital adrenal hypoplasia; ;NM_000475.4:c.1130A>GHomozygousAutosomal, RecessiveWalker et al. 2012 First cousin, once r...
300200.2.1OmanMaleYesYes Congenital adrenal hypoplasia; ;NM_000475.4:c.857_862delHomozygousAutosomal, RecessiveWalker et al. 2012
300200.2.2OmanMaleYesYes Congenital adrenal hypoplasia; ;NM_000475.4:c.857_862delHomozygousAutosomal, RecessiveWalker et al. 2012 Brother of 300200.2....
300200.2.3OmanMaleYesYes Congenital adrenal hypoplasia; ;NM_000475.4:c.857_862delHomozygousAutosomal, RecessiveWalker et al. 2012 Brother of 300200.2....
300200.2.4OmanMaleYesYes Congenital adrenal hypoplasia; ;NM_000475.4:c.857_862delHomozygousAutosomal, RecessiveWalker et al. 2012 Brother of 300200.2....
300200.G.1OmanMaleYesYes Congenital adrenal hypoplasia; Death in...NM_000475.4:c.857_862delHomozygousAutosomal, RecessiveWalker et al. 2012 Relatives of 300200....
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