Pubertal timing in children with Silver Russell syndrome compared to those born small for gestational age

Abstract

ContextData on pubertal timing in Silver Russell syndrome (SRS) are limited.Design and methodsRetrospective observational study including twenty-three SRS patients [11p15 loss of methylation, (11p15 LOM, n=10) and maternal uniparental disomy of chromosome 7 (mUPD7, n=13)] and 21 small for gestational age (SGA). Clinical (thelarche in females; testis volume ≥ 4 ml in males; pubarche), BMI SD trend from the age of 5 to 9 years to the time of puberty, biochemical parameters of puberty onset [Luteinizing hormone (LH), 17-β-estradiol, testosterone], and bone age progression were evaluatedResultsPubertal onset and pubarche occurred significantly earlier in children with SRS than in SGA (p 0.03 and p 0.001, respectively) and clinical signs of puberty onset occurred earlier in mUPD7 than in 11p15LOM group (p 0.003). Five SRS children experienced central precocious puberty and LH, 17-β-estradiol, testosterone were detected earlier in SRS than in SGA (p 0.01; p 0.0001). Bone age delay in SRS children was followed by rapid advancement; the delta between bone age and chronological age in SRS group became significantly higher than in SGA group at the age of 9-11 years (p 0.007). 11p15LOM patients were underweight at the age of 5 years and showed a progressive normalization of BMI that was significantly higher than in mUPD7 (p 0.04) and SGA groups (p 0.03) at puberty onset.ConclusionTiming of puberty is affected in SRS and occurred earlier in mUPD7 compared to 11p15LOM. The impact of early puberty on adult height and metabolic status deserves long-term evaluation.

Pubertal growth in children born small for gestational age (SGA) with persistent short stature (SGA-SS). Growth hormone treatment outcomes from data of the Czech countywide REPAR database

“…(28) Puberta nastává jednoznačně časně u obou podskupin dětí se syndromem Silvera-Russella -zejména u nositelů maternální uniparentální disomie na 7. chromozomu (mUPD7), ale také u dětí se ztrátou metylace v oblasti 11p15 (11p15 LOM). (29) Naše výsledky prokazují, že hlavní příčinou menšího úspěchu pubertálního růstového období je nedostatečný pubertální růstový výšvih. Léčba růstovým hormonem již nedává většině dětí s endogenní příčinou SGA šanci v pubertě výšku dále zlepšit.…”

Growth response of syndromic versus non-syndromic children born small for gestational age (SGA) to growth hormone therapy: a Belgian study

“…The pubertal height gain of syndromic patients was lower, thus they ended up shorter than non-syndromic patients. This could be due to the fact, that SRS patients accounted for 15% of the syndromic patients and that SRS patients present an earlier pubertal onset (18) and an earlier adrenarche than other SGA patients (31). SRS boys with an early adrenarche are known to be taller at gonadarche but to end up as short as the boys with normal adrenarche (32).…”