Although pure gonadal dysgenesis with male
pseudohermaphroditism is typical, the clinical variability of the external
genitalia ranges from bifid scrotum with micropenis and palpable gonads to
penoscrotal hypospadias with cryptorchidism or clitoral hypertrophy with
labial fusion. Gonadal dysgenesis presents as streak ovaries and dysgenetic
testes, respectively. Usually, patients present in their first year of life
with the typical symptoms of nephrotic syndrome (marked proteinuria with
hypoproteinemia [hypalbuminemia] resulting in recurrent infections, marked
edema, abdominal distension secondary to ascites, hyperlipidemia, and
hypercholesterolemia). Patients may have varying degrees of renal
dysfunction/failure, but glomerular filtration rate usually declines quickly
and results in end-stage renal disease requiring either dialysis or renal
transplantation at approximately age 3 years. Hypertension, failure to
thrive, and delayed psychomotor milestones may develop as a result of renal
failure. Wilms tumor is usually detected at approximately age 2 years and is
most often unilateral (80%). However, bilateral nephrectomy may be
prudent management for unilateral nephropathy to reduce the high likelihood
of developing a Wilms tumor in the contralateral kidney. Elective
gonadectomy can be performed because of the difficulty in screening for
gonadal malignancies. Most associated findings probably are incidental.