C-17 Hydroxylase Deficiency Clinical Presentation

Updated: Feb 01, 2018
  • Author: Gabriel I Uwaifo, MD; Chief Editor: George T Griffing, MD  more...
  • Print


Typically, 17-hydroxylase deficiency is first recognized in puberty, with the discovery of hypertension, hypokalemia, and hypogonadism. Patients present as phenotypic females, with sexual infantilism and primary amenorrhea. Patients with the condition who are genetic males (XY) typically present with complete male pseudohermaphroditism; they are characterized by external female genitalia, with a blind-ending vagina, but no uterus or fallopian tubes, present. These patients tend to have intra-abdominal testes. Less severely affected XY patients may present earlier in life with ambiguous genitalia due to underproduction of androgens. Typically, male patients have been raised as females, with the condition being identified only during puberty, when the expected pubertal changes have not occurred (and have therefore led to an in-depth investigation).

  • Approximately 90% of patients are hypertensive or hypokalemic at presentation.

  • Less commonly, the presentation may include malignant hypertension. [15]

  • Severe hypokalemia associated with muscle weakness, abdominal distension, or intestinal obstruction may be a predominant feature.

  • In classic 17-hydroxylase deficiency, patients with XX or XY karyotypes are phenotypic females. Both present with lack of secondary sexual development.

    • The testes of 46,XY patients do not produce testosterone in utero, resulting in absence of masculinization of the external genitalia. However, normal production of müllerian inhibitory substance occurs, resulting in müllerian duct regression. Thus, these patients have a blind vagina, absence of müllerian structures (fallopian tubes, uterus, and upper one third of vagina), and female external genitalia.

    • Patients with 46,XY karyotype and incomplete deficiency may present with ambiguous genitalia. Occasionally, these patients may be misdiagnosed with androgen insensitivity or other defects in androgen production.

  • Because this syndrome is autosomal recessive, a screening history of potentially affected pedigrees needs to exclude the possibility of consanguinity, closed communities with significant inbreeding, and the possibility of a founder effect.

  • Partial 17-hydroxylase deficiency (nonclassic variant) has been described in a few families in the setting of consanguinity. [16]

    • The clinical phenotype is less severe, and XY patients may present with microphallus, perineoscrotal hypospadias, scrotal testes, and mild hypertension.

    • XX patients typically are infertile and have hypertension, irregular menses or primary amenorrhea, and hypoplastic breasts.

    • The hypogonadism associated with the condition is associated with bone age retardation and osteoporosis.

    • Patients fail to have a distinct adrenarche or pubarche.



In the classic variants, 46,XY and 46,XX patients present as phenotypic females.

  • XX and XY patients

    • Hypertension is common. [15]

    • Secondary sexual characteristics, including axillary and pubic hair, are absent.

    • Breasts and genitalia are infantile.

    • Patients may be tall, with eunuchoid proportions due to a lack of sex steroids (and thus, delayed fusion of epiphysis).

  • Patients who are 46,XX - Internal female genitalia are normal but underdeveloped.

  • Patients who are 46,XY

    • The external genitalia are female, but they do not have the corresponding internal müllerian structures (eg, uterus, fallopian tubes, ovaries).

    • In utero, these patients do not have significant testosterone production, but the production of müllerian inhibitory factor from the testes is normal, preventing the development of female internal structures.

    • Patients may have inguinally located testes that may present as inguinal hernias.



The human CYP17 gene codes for the 508 amino acid enzyme, which has a molecular weight of approximately 57,000.

  • The enzyme has 17,20-lyase and 17-alpha-hydroxylase activities. [13]

  • The gene consists of 8 exons.

Most of the described clinical cases of 17-hydroxylase deficiency are associated with small base substitutions or insertions, resulting in premature peptide termination, on the gene located in the 10q24-25 band. Single or multiple codon deletions, as well as large deletions, nonsense mutations, and missense mutations, have also been described. [17] Overall, about 40 different mutations of the gene have been described so far. No strong genotype-phenotype correlation exists in 17-hydroxylase deficiency.

As with other variants of congenital adrenal hyperplasia, 17-hydroxylase deficiency is an autosomal recessive disease.

Most mutations are random and spontaneous.

  • Clusters of patients with the same mutation have been identified in Holland, Brazil, and Japan, suggesting a founder effect.

  • Mutations that retain partial enzymatic activity also have been described.

  • A very rare variant featuring combined CYP21A2 and CYP17 deficiency has been described; it appears to result from mutations in the gene for P450 oxidoreductase rather than from mutations in either the CYP17 or CYP21A2 genes.