A 3-hour-old newborn is being evaluated in the nursery. The patient was born at 37 weeks gestation via spontaneous vaginal delivery to a 32-year-old woman. The mother had regular prenatal care and no complications during the pregnancy or delivery. Family history is unremarkable. The patient measures at the 50th percentile for weight and head circumference. Length is at the 75th percentile. Examination shows a vigorously crying newborn who soothes easily. The anterior fontanelle is open, soft, and flat. The patient has a strong suck reflex, and the neck appears normal. The eyes appear normally spaced. Chest examination is normal with equal breath sounds bilaterally. The abdomen is soft and has no organomegaly. Urogenital examination shows curvature of an underdeveloped phallus with the urethral meatus at the base. Labioscrotal folds are fused, and the gonads are not palpable. The 17-hydroxyprogesterone level is elevated. Which of the following is the most likely karyotype in this patient?
Classic congenital adrenal hyperplasia | |
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*Clinical symptoms & electrolyte abnormalities develop at age 1-2 weeks. | |
This patient has ambiguous genitalia and elevated 17-hydroxyprogesterone (17-OHP), findings characteristic of congenital adrenal hyperplasia (CAH). CAH is most commonly due to a deficiency of 21-hydroxylase, an enzyme whose substrate is 17-OHP. Deficiency results in decreased cortisol production and increased 17-OHP and androgen production. Excess androgen leads to virilization in female (46,XX) infants; male (46,XY) infants are phenotypically normal or hypervirilized (eg, enlarged phallus) (Choice B).
Signs of female virilization include clitoral enlargement, which can appear as an underdeveloped phallus with an ectopic urethral meatus (ie, hypospadias), as seen in this patient. Labioscrotal folds may be partially or completely fused. Gonads are nonpalpable because female patients with CAH have internal female organs and do not have testes.
Initial evaluation of ambiguous genitalia includes karyotype to confirm genotype and pelvic ultrasound to assess for presence of female internal organs. Serum electrolytes should be obtained to screen for salt-wasting forms of CAH, which can result in life-threatening adrenal crisis.
(Choice A) Neonates with Turner syndrome (45,X) may have lymphedema of the hands and feet, a broad chest, and webbed neck, not seen in this patient. Primary amenorrhea due to gonadal dysgenesis or short stature may be presenting signs. Virilization is not seen.
(Choice D) Most boys with Klinefelter syndrome (47,XXY) are phenotypically normal at birth. After puberty, patients classically have small testes and infertility. An underdeveloped phallus, hypospadias, and elevated 17-OHP level would not be seen.
(Choice E) XYY syndrome (47,XYY) may be asymptomatic or present with tall stature, severe acne, and learning disabilities in adolescents. Infants with this syndrome have normal male genitalia and bilateral descended testes. In contrast, no gonads are palpable in this patient.
Educational objective:
Congenital adrenal hyperplasia is most commonly due to 21-hydroxylase deficiency, which results in decreased cortisol and increased 17-hydroxyprogesterone and androgen production. Excess androgen leads to virilization (eg, underdeveloped phallus, hypospadias) in female (46,XX) infants.