Hypogonadism and pubertal development in Prader-Willi syndrome

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Prader-Willi Syndrome (PWS) is associated with genital abnormalities and pubertal development disorders, including hypogonadism.
• Previous studies on PWS genital findings often lacked genetic confirmation.
• Comprehensive evaluation of these issues in PWS is crucial for diagnosis and management.

Purpose of the Study:

• To describe external genital findings and spontaneous pubertal development in a cohort of genetically confirmed PWS patients.
• To evaluate the prevalence of specific genital abnormalities and pubertal milestones in males and females with PWS.
• To assess the diagnostic significance of hypogonadism in PWS.

Main Methods:

• Study included 84 patients (42 males, 42 females) with PWS, aged 2.1 to 35.4 years.
• Diagnosis of PWS was confirmed using Holm and Cassidy criteria and genetic testing (methylation test and/or FISH).
• Evaluated external genitalia, testicular volume, penile length, age of menarche, menstrual cycle characteristics, and onset of puberty.

Main Results:

• All males exhibited cryptorchidism (86% bilateral); 90% underwent orchidopexy. Small testes (76%) and scrotal hypoplasia (69%) were common.
• In females, 76% showed hypoplasia or absence of labia minora and/or clitoris.
• Spontaneous menarche occurred in 44% after age 15, often with irregular cycles; 56% had primary amenorrhea. Precocious puberty was observed in 3.6%.

Conclusions:

• Hypogonadism is a significant clinical feature in PWS, underscoring its diagnostic importance.
• Cryptorchidism is a universal finding in males with PWS.
• Many PWS patients do not complete puberty spontaneously; hormonal therapy should be individualized.