Genital abnormalities are common in
Prader-Willi Syndrome (PWS) and are one of the eight major clinical
criteria for diagnosis. Previous reports of the type and frequencies of
these abnormalities were not necessarily from individuals with genetically
confirmed PWS. Crino and associates report data from patients evaluated by
the Genetic Obesity Study Group of the Italian Society of Pediatric
Endocrinology and Diabetology. Eighty-four patients (42 males), mean age
15.8±8.2 years were studied. Sixty-three percent were over 14-years-old.
All satisfied the Holm and Cassidy clinical criteria for the diagnosis of
PWS and the methylation test was positive in all subjects. Microdeletion
of chromosome 15(15q12-13) was demonstrated in 66%, while uniparental
disomy or an imprinting defect was suspected in the others.
All males showed cryptorchidism (86% bilateral). Small testes and
scrotal hypoplasia were observed in 76% and 69%, respectively. Micropenis
was seen in 36%. Twenty-two of 29 males had spontaneous onset of puberty
at 14.0±3.2 years but it was incomplete in all cases. Specifically,
pubertal changes past Tanner 2-3 genital stages were rarely observed.
In females there was hypoplasia of the labia minora and/or of the
clitoris in 71% and 69% of cases. Thirty-four of 39 females had
spontaneous onset of puberty at 12.6±2.7 years, with very slow
progression. Menarche occurred at a mean age of 17.3±5.2 years in 44% of
cases over 14 years of age. Primary amenorrhea was diagnosed in 56%.
Menstrual cycles were seldom regular and secondary amenorrhea occurred in
33% who had spontaneous menarche. Of note, premature pubarche occurred in
12 subjects (6 males) and true precocious puberty in 3. It is suggested
that premature pubarche might have been related to obesity. Genital and
pubertal abnormalities were evenly distributed among subjects with
microdeletion and UPD-imprinting defects. Treatment of various types for
hypogonadism was discussed, including the use of dihydrotestosterone
transdermally. However, no systematic trials on treatment with sex hormone
treatment in adolescents or adults are available.
Crino A et al. Eur J Pediatr 2003;162:327-333.
Editor’s Comment: This paper provides interesting information
concerning genital abnormalities in individuals diagnosed with PWS,
confirmed with genetic testing. The large number of subjects in this
descriptive study and the careful presentation of the findings should
assist all who work with these patients and who must counsel them and
their families in regard to expectations for pubertal development and
fertility. It is interesting that sexual precocity was observed at a
frequency that should be considered high in this group. This suggests that
examination of the genitalia should be performed at each clinical visit.
Whether or not current treatment with exogenous GH, which has been shown
to significantly alter body composition in PWS, will affect pubertal
development remains to be shown.
William L. Clarke, MD
