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

STUDY QUESTION: Is gonadal function affected in males and females with Silver-Russell Syndrome (SRS)? SUMMARY ANSWER: Sertoli cell dysfunction is more common in males with SRS, with 11p15 LOM, but gonadal function seems to be unaffected in females with SRS. WHAT IS KNOWN ALREADY: Males with SRS have an increased risk for genital abnormalities such as cryptorchidism and hypospadias, which could be associated with reproductive problems in later life. In SRS females, an association has been described with Mayer-Rokitansky-Küster-Hauser syndrome, which might compromise their reproductive function. STUDY DESIGN, SIZE, DURATION: Longitudinal follow-up study, involving 154 subjects, over a time period of 20 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Thirty-one SRS patients (14 males) and 123 non-SRS patients born at same gestational age (SGA; 65 males). All received growth hormone and 27.3% received additional gonadotropin-releasing hormone analog treatment (GnRHa). MAIN RESULTS AND THE ROLE OF CHANCE: Mean age at onset of puberty was 11.5 years in SRS males versus 11.6 years in non-SRS males (P = 0.51), and 10.5 years in SRS females versus 10.7 years in non-SRS females (P = 0.50). Four of the 14 SRS males had a post-pubertal inhibin-B level below the fifth percentile compared to healthy controls, and two of them an FSH above the 95th percentile, indicating Sertoli cell dysfunction. One of them had a history of bilateral cryptorchidism and orchiopexy. All SRS females had AMH, LH and FSH levels within the reference range. Pubertal duration to Tanner stage five was similar in SRS and non-SRS. Pubertal height gain was better in SRS patients who additionally received GnRHa (P < 0.01). Mean age at menarche was 13.1 years in SRS versus 13.3 years in non-SRS (P = 0.62). One SRS female had primary amenorrhea due to Müllerian agenesis. LIMITATIONS, REASONS FOR CAUTION: As this is a rare syndrome, the SRS group had a small size. WIDER IMPLICATIONS OF THE FINDINGS: As gonadal function is not affected in females with SRS, it is likely that reproductive function is also not affected. Sertoli cell dysfunction in males with SRS could cause impaired reproductive function and should be assessed during pubertal development. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for the study. The authors have no conflicts of interest.

[A toddler with a swelling of his penis]. / Een kleuter met een zwelling aan zijn penis.

A 4-year-old boy presented with a subcutaneous, yellowish swelling of 0.8 by 1.5 cm on his penis. We made the diagnosis of a smegma retention cyst. This cyst is the result of a physiologic phenomenon that originates from the separation of the foreskin.

Long-Term Results of GH Treatment in Silver-Russell Syndrome (SRS): Do They Benefit the Same as Non-SRS Short-SGA?

CONTEXT: Silver-Russell syndrome (SRS) is a genetically heterogeneous syndrome characterized by low birth weight, severe short stature, and variable dysmorphic features. GH treatment is a registered growth-promoting therapy for short children born small for gestational age, including SRS, but there are limited data on the GH response in SRS children and on differences in response among the (epi)genetic SRS subtypes (11p15 aberrations, maternal uniparental disomy of chromosome 7 [mUPD7], and idiopathic SRS). OBJECTIVES: To compare growth and adult height between GH-treated small for gestational age children with and without SRS (non-SRS), and to analyze the difference in GH response among SRS genotypes. DESIGN AND SETTING: A longitudinal study. PARTICIPANTS: Sixty-two SRS and 227 non-SRS subjects. INTERVENTION: All subjects received GH treatment (1 mg/m(2)/d). MAIN OUTCOME MEASURES: Adult height and total height gain. RESULTS: The SRS group consisted of 31 children with 11p15 aberrations, 11 children with mUPD7, and 20 children with idiopathic SRS. At the start of GH treatment, mean (SD) height standard deviation score [SDS] was significantly lower in SRS (-3.67 [1.0]) than in non-SRS (-2.92 [0.6]; P < .001). Adult height SDS was lower in SRS (-2.17 [0.8]) than in non-SRS (-1.65 [0.8]; P = .002), but the total height gain SDS was similar. There was a trend toward a greater height gain in mUPD7 than in 11p15 (P = .12). CONCLUSION: Children with SRS have a similar height gain during GH treatment as non-SRS subjects. All (epi)genetic SRS subtypes benefit from GH treatment, with a trend toward mUPD7 and idiopathic SRS having the greatest height gain.