Gonadal function and pubertal development in patients with Silver-Russell syndrome

Area of Science:

• Endocrinology
• Reproductive Medicine
• Genetics

Background:

• Silver-Russell Syndrome (SRS) is a rare genetic imprinting disorder characterized by intrauterine and postnatal growth retardation.
• Previous studies suggest potential reproductive challenges in both males and females with SRS, including genital abnormalities and associations with conditions like Mayer-Rokitansky-Küster-Hauser syndrome.

Purpose of the Study:

• To investigate the impact of Silver-Russell Syndrome (SRS) on gonadal and pubertal development in both males and females.
• To assess reproductive function in SRS patients, particularly in relation to growth hormone and gonadotropin-releasing hormone analog treatments.

Main Methods:

• A longitudinal follow-up study was conducted over 20 years with 154 subjects.
• The study included 31 SRS patients (14 males) and 123 non-SRS patients born at the same gestational age (SGA).
• Hormonal levels (Inhibin-B, FSH, AMH, LH) and pubertal milestones (age of onset, duration, menarche) were analyzed.

Main Results:

• Pubertal onset and duration were similar between SRS and non-SRS groups for both males and females.
• Four out of 14 SRS males exhibited Sertoli cell dysfunction (low inhibin-B or high FSH), with one having a history of cryptorchidism.
• All SRS females had normal AMH, LH, and FSH levels; one experienced primary amenorrhea due to Müllerian agenesis.

Conclusions:

• Gonadal function appears unaffected in females with Silver-Russell Syndrome (SRS), suggesting preserved reproductive potential.
• Sertoli cell dysfunction is present in a subset of males with SRS, indicating a potential risk for impaired reproductive function that warrants monitoring.
• Growth hormone treatment, especially with adjunctive GnRHa, may improve pubertal height gain in SRS patients.