ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Hum Reprod. 2018 Nov 1;33(11):2122–2130

This longitudinal study of 31 patients (14 males) with Silver-Russell syndrome (SRS) and 123 non-SRS small-for-gestational-age (SGA) patients (65 males) shows that Sertoli cell dysfunction is more common in SRS males, with 11p15 loss of methylation (LOM), but gonadal function seems to be unaffected in SRS females.

Literature describes that SRS males have an increased risk of genital abnormalities (1, 2) while SRS in females is associated with Mayer–Rokitansky–Küster–Hauser syndrome (3). However, data on gonadal function and fertility in patients with SRS are lacking.

These authors describe a longitudinal study, which analyzed gonadal function and pubertal progression in SRS patients from childhood until early adulthood. These data were compared to those of patients born SGA without SRS. Onset and progression of puberty were similar in SRS and non-SRS SGA children. However, Sertoli cell dysfunction was more common in SRS males than non-SRS SGA males: >25% of SRS males had a low post-pubertal inhibin B level <5th percentile on normal references; two SRS males also had a high FSH level >95th percentile. Gonadal function did not seem to be impaired in females with SRS.

This is the first study looking at gonadal function in patients with SRS. More research is warranted to investigate the etiology of Sertoli cell dysfunction in SRS males, especially those with a loss of methylation in 11p15, who appear to have an increased risk of gonadal dysfunction.

References: 1. Price SM, Stanhope R, Garrett C, Preece MA, Trembath RC. 1999 The spectrum of Silver-Russell syndrome: a clinical and molecular genetic study and new diagnostic criteria. J Med Genet. 36:837–842.

2. Bruce S, Hannula-Jouppi K, Peltonen J, Kere J, Lipsanen-Nyman M. 2009 Clinically distinct epigenetic subgroups in Silver-Russell syndrome: the degree of H19 hypomethylation associates with phenotype severity and genital and skeletal anomalies. J Clin Endocrinol Metab. 94:579–587.

3. Abraham MB, Carpenter K, Baynam GS, Mackay DJ, Price G, Choong CS. 2014 Report and review of described associations of Mayer–Rokitansky– Kuster–Hauser syndrome and Silver–Russell syndrome. J Paediatr Child Healt. 51:555–560.

4. Bellver-Pradas J, Cervera-Sanchez J, Boldo-Roda A, Martin-Cortes A, Ferreres-Gomez L, Serra-Serra V, Romeu-Sarrio A. 2001 Silver-Russell syndrome associated to Mayer–Rokitansky–Kuster–Hauser syndrome, diabetes and hirsutism. Arch Gynecol Obstet. 265: 155–157.