Adult height and epigenotype in children with Silver-Russell syndrome treated with GH

To compare adult heights of GH-treated and GH-untreated patients with Silver-Russell syndrome (SRS) who were epigenotyped.

This was a nonrandomized retrospective study with matched controls at a single center. Molecular analysis of 32 out of 37 GH-treated patients (16 females) revealed IGF2-H19 epimutations in 12 and maternal uniparental disomy of chromosome 7 (matUPD7) in 5 patients; 15 were negative. At start of GH, mean age was 7.2 years and mean height -3.34 standard deviation score (SDS). Mean GH dose used was 51 µg/kg·day, mean duration of therapy was 5.6 years. Puberty was blocked by GnRH analogs in 16 patients. The untreated group comprised 13 individuals (5 females, mean age 6.8 years and mean height -3.34 SDS). End points were adult height and overall height gain.

GH-treated patients reached an adult height of -2.12 ± 0.98 SDS gaining 1.22 SDS in comparison to baseline. Adult height SDS of the untreated was -3.13 ± 1.37 SDS. The matched treated patients were significantly taller than their untreated counterparts. Outcome was dependent on height at start of GH and duration of therapy. Height gain was highest in the shortest patients.

GH improved adult height in SRS to a comparable degree as reported in nonsyndromic SGA children. A trend toward a better outcome in matUPD7 needs confirmation in larger cohorts.