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5-Alpha-Reductase Deficiency Clinical Presentation

  • Author: Jill E Emerick, MD; Chief Editor: Stephen Kemp, MD, PhD  more...
 
Updated: May 29, 2014
 

History

Diagnosis of 5-alpha-reductase type 2 deficiency (5-ARD) is usually made in the newborn period when the infant presents with ambiguous genitalia.[12] No risk factors or clinical markers in pregnancy are known. Genital ambiguity is occasionally diagnosed prenatally when an infant who is demonstrated by amniocentesis or chorionic villus sampling to have XY karyotype fails to have a demonstrable penis on ultrasonography.

If 5-alpha-reductase deficiency is considered in a newborn, a broad approach to ambiguous genitalia should be taken.[1, 11] The utmost care should be taken not to assign a gender to the child before evaluation and consultation with an experienced, multidisciplinary team. The first words spoken to the parents are likely to be remembered and should focus on the overall health of the infant. A sensitive discussion about the uncertainty of the child's gender and explanation of the child's genital anatomy can be aided by online developmental Web sites, such as the ones available on the Sick Kids and DSD Guidelines sites. See Ambiguous Genitalia and Intersexuality for more in depth discussion

Initial evaluation should begin with a careful history.[1] Assess prenatal and maternal past medical and family history. Specific questions should be asked regarding relatives with disorders of sexual development (DSDs), neonatal deaths, amenorrhea, or infertility and consanguinity. Parental consanguinity increases the child's risk for autosomal recessive disorders including 5-alpha reductase type 2 deficiency.

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Physical

Workup of ambiguous genitalia must include careful physical examination to characterize the degree of virilization on the Prader scale (see the image below), presence of palpable gonadal tissue, and overall health of the child.[11]

Prader scale reflecting the degree of virilization Prader scale reflecting the degree of virilization of the external genitalia. The internal genitalia reflect the changes in the urogenital sinus in response to the presence or absence of mullerian inhibiting hormone (MIH)

Neonatal presentation

Phenotypic findings in a newborn are limited to the genitalia.[12, 19] The spectrum of findings ranges from minimal undervirilization presenting with normal male anatomy, except for isolated micropenis or hypospadias, to severe undervirilization presenting as normal female external genitalia with mild clitoral enlargement as the only physical finding. In a recent study, a cohort of 55 patients with 5-alpha-reductase type 2 deficiency displayed varied phenotypes in the neonatal period. In this cohort, clitoromegaly was the most common phenotype in 49% of patients, followed by microphallus with varying degrees of hypospadias in 33% of patients.[20]

Most commonly, the external genitalia exhibit labial appearance to the labioscrotal folds with some mild rugation or pigmentation present in some patients.

The phallus is indeterminate in size. Its length falls between 1 cm (ie, usual maximum for a clitoris) and 2 cm (ie, lower limit of normal for a penis).

The urethra may empty anywhere from the tip of the phallus to the perineum, with the latter observed more often.

The testes are usually in the inguinal canals bilaterally; however, in some individuals with 5-alpha-reductase type 2 deficiency, the testes can be found in the labioscrotal folds or retained in the abdomen.

A pseudovaginal blind-ending introitus is usually present with a normal hymen.

Because the uterus is absent, rectal examination results are negative for a cervical mass.

The rest of the examination findings are within normal limits.

Presentation of 46XY males at puberty

Clear signs of virilization predominate at this age. The escutcheon is male in distribution. The phallus exhibits definite enlargement. The shoulders are relatively broad and the hips are narrow.

Muscularity and body hair may increase. Generally, no breast development is present. A prominentia laryngea (Adam's apple) may start to develop. In addition, facial hair develops and the child's voice may begin to deepen.

The mucosa of the vaginal introitus remains atrophic in appearance (remaining red) rather than the thickened pink of estrogen-stimulated mucosa.

Presentation of 46XX females

Females homozygous for 5-alpha-reductase type 2 deficiency have very subtle manifestations, such as delayed menarche, minimal acne, and minimal body hair.[21] Fertility is normal in females.

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Causes

The cause of 5-alpha-reductase type 2 deficiency is the deficiency of the type 2 isozyme of 5-alpha-reductase.

As with most single enzyme disorders, 5-alpha-reductase type 2 deficiency is an autosomal recessive trait and sex limited because the clinical syndrome only affects genetic males, with very subtle phenotypic findings in homozygous females.[22]

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Contributor Information and Disclosures
Author

Jill E Emerick, MD Staff Pediatric Endocrinologist, Walter Reed National Military Medical Center, Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences

Jill E Emerick, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Andrew J Bauer, MD Director, The Thyroid Center, Division of Endocrinology, The Children's Hospital of Philadelphia

Andrew J Bauer, MD is a member of the following medical societies: American Academy of Pediatrics, American Thyroid Association, Pediatric Endocrine Society, Endocrine Society

Disclosure: Nothing to disclose.

Noelle Summers Larson, MD Fellow in Pediatric Endocrinology, Uniformed Services University of the Health Sciences; Attending Physician, Department of Pediatrics, Walter Reed Army Medical Center/National Naval Medical Center

Noelle Summers Larson, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Medical Association, Endocrine Society, Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Ruth S Faircloth, MD Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences; Fellow in Pediatric Endocrinology, Walter Reed National Military Medical Center

Ruth S Faircloth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Barry B Bercu, MD Professor, Departments of Pediatrics, Molecular Pharmacology and Physiology, University of South Florida College of Medicine, All Children's Hospital

Barry B Bercu, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Pediatric Endocrine Society, Society for Pediatric Research, Southern Society for Pediatric Research, Society for the Study of Reproduction, American Federation for Clinical Research, Pituitary Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD Former Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Phyllis W Speiser, MD Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's Medical Center of New York; Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine at Hofstra University

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

References
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Biochemical effects of 5-alpha-reductase type 2 deficiency in testosterone biosynthesis. Typically levels of testosterone are elevated, whereas levels of dihydrotestosterone (DHT) are significantly decreased, leading to male undervirilization.
Prader scale reflecting the degree of virilization of the external genitalia. The internal genitalia reflect the changes in the urogenital sinus in response to the presence or absence of mullerian inhibiting hormone (MIH)
 
 
 
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