Etiologic classification of severe hypospadias: implications for prognosis and management.
OBJECTIVE
Classification of severe hypospadias employing a broad array of diagnostic tools. Standardization of a diagnostic approach to children with hypospadias. Indentification of patients at risk of having malignancies and endocrine problems.


METHODS
Retrospective analysis of patients in a single-center study.


METHODS
Thirty-three patients with severe (scrotal or penoscrotal) hypospadias, aged 1 to 18 years.


METHODS
Clinical assessment, ultrasonography, karyotyping, endocrine evaluation including adrenal steroid concentrations, sex hormone-binding globulin test for androgen sensitivity, human chorionic gonadotropin stimulation with determination of testosterone and dihydrotestosterone concentrations to exclude 5 alpha-reductase deficiency, and molecular genetic analysis of the androgen receptor gene and the 5 alpha-reductase gene.


RESULTS
In 12 patients the cause was clarified. Diagnoses included Drash syndrome with Wilms tumor in infancy (3 patients), partial androgen insensitivity resulting from androgen receptor mutations (2), true hermaphroditism (2), chromosomal aberration (1), deficiency of antimüllerian hormone (1), gonadal dysgenesis (1), partial 5 alpha-reductase deficiency caused by a novel point mutation (1), and XX-male syndrome (1). Twelve patients had associated findings such as cardiac malformations (3 patients), rectal atresia (1), dilation of urinary tract (2), cystinuria (1), and others.


CONCLUSIONS
Patients with severe hypospadias should be submitted to a standardized set of diagnostic procedures in infancy. A stepwise diagnostic study avoids unnecessary, invasive, and expensive testing. A high proportion of classified causes can be expected. Patients at risk of having malignancies or hormonal disorders must remain under close surveillance.
Albers
N
N
Department of Pediatrics, University of Bonn, Germany.
Ulrichs
C
C
Glüer
S
S
Hiort
O
O
Sinnecker
G H
GH
Mildenberger
H
H
Brodehl
J
J
D000293:Adolescent; D000465:Algorithms; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003663:Decision Trees; D003937:Diagnosis, Differential; D012734:Disorders of Sex Development / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D007021:Hypospadias / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index