![]() Measurement of 17-hydroxyprogesterone (17-OHP) with or without ACTH stimulation establishes the diagnosis of CAH due to 21-OHD. Nonclassic: 46,XY variable degrees of genital ambiguity, adrenal insufficiency.Ĭholesterol side-chain cleavage enzyme deficiencyĬlassic: phenotypic female (46,XX or 46,XY sex reversal), adrenal insufficiency, salt-wasting.Ībbreviations: CAH, congenital adrenal hyperplasia CAH-X, congenital adrenal hyperplasia with tenascin-X impairment StAR, steroidogenic acute regulatory protein Post-natal virilization does not occur.Ĭlassic: phenotypic female (46,XX or 46,XY sex reversal), adrenal insufficiency, severe salt-wasting Possible skeletal malformations (Antley-Bixler syndrome). Partial: 46,XY variable degrees of genital ambiguity.Ĥ6, XX variable development of secondary sexual characteristics.ģβ-hydroxysteroid dehydrogenase type 2 deficiencyĬlassic: 46,XX and 46,XY ambiguous genitalia, adrenal insufficiency, salt-wasting.Ĥ6,XX and 46,XY ambiguous genitalia, adrenal insufficiency, severe salt-wasting, possible maternal virilization during pregnancy. May be asymptomatic.Ĭlassic: female phenotype (46,XX or 46,XY sex reversal), hypertension, pubertal delay with absence of secondary sexual characteristics. Nonclassic: hyperandrogenism during childhood or early adulthood. Nonclassic: hyperandrogenism during childhood or early adulthood may be asymptomatic.ĬAH-X: In addition to the above, joint hypermobility, joint pain, multiple joint dislocations, midline defects including possible cardiac structural abnormalities.Ĭlassic: 46,XX ambiguous genitalia, postnatal virilization, hypertension. 4 Other less common forms of CAH include: 3β-hydroxysteroid dehydrogenase type 2 deficiency, 17α-hydroxylase deficiency that is more commonly seen in Mennonite descendants of Dutch Frieslander and the Brazilian population congenital lipoid adrenal hyperplasia that is more commonly seen in the Japanese and Korean populations side-chain cleavage enzyme deficiency that is most commonly found in Turkey and cytochrome P450 oxidoreductase deficiency (ORD), the only variant that can manifest with skeletal malformation.Ĭlassic: 46,XX ambiguous genitalia, adrenal insufficiency, salt-wasting, postnatal virilization. 3 The second most common form of CAH, 11-hydroxylase deficiency (11-OHD), occurs in 1 in 100,000 live births in the general population and accounts for approximately 5% of cases. 2 NCCAH is one of the most common autosomal recessive disorders in humans and affects approximately 1 in 1,000 individuals. 1 The classic type affects approximately 1 in 16,000 live births. 21-OHD is classified into 3 subtypes according to clinical severity: classic salt-wasting (SW), classic simple virilizing (SV), and nonclassic (NCCAH, mild or late-onset). Over 95% of all cases of CAH are caused by 21- hydroxylase deficiency (21-OHD). The severity and clinical features of CAH vary depending on the enzymatic defect, its residual activity, age of presentation, and genotype.ĬAH represents a continuous phenotypic spectrum ( Table 1). The biochemical defects in CAH translate to a spectrum of clinical consequences, which include adrenal insufficiency, genital ambiguity or disordered sex development (DSD), infertility, short stature, hypertension, and an increased risk of metabolic syndrome during adolescence and adulthood. This leads to defective cortisol synthesis, shunting of the accumulated steroid precursors through alternative pathways, and often adrenal gland hyperplasia. Consequently, overproduction of corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) from the hypothalamus and pituitary glands, respectively, results in an increase and accumulation of various steroid precursors proximal to the block. In this article, we provide an in-depth discussion on the genetics of CAH, including genetic diagnosis, molecular analysis, genotype-phenotype relationships and counseling of patients and their families.Ĭongenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive disorders that impair cortisol biosynthesis. Several pitfalls in the genetic diagnosis of patients with CAH exist. Certain ethnic groups have a predilection to certain genotypes, which may have resulted from an ancient founder effect, a hot spot in the gene, unequal crossing over during meiosis or gene conversion of point mutations from a pseudogene. The genes for the various variants of CAH are well characterized, and mutation analysis is widely available. ![]() Genotyping is an important tool in confirming the diagnosis or carrier state, provides prognostic information on disease severity, and is essential for genetic counseling. ![]() CAH represents a continuous phenotypic spectrum with over 95% of all cases caused by 21-hydroxylase deficiency. Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive disorders due to single gene defects in the various enzymes required for cortisol biosynthesis.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |