Adult height and epigenotype in children with Silver-Russell syndrome treated with GH.
OBJECTIVE
To compare adult heights of GH-treated and GH-untreated patients with Silver-Russell syndrome (SRS) who were epigenotyped.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Paediatric Endocrinology, University Children's Hospital, Tübingen, Germany.
G
G
Binder
M
M
Liebl
J
J
Woelfle
T
T
Eggermann
G
G
Blumenstock
R
R
Schweizer
D000293:Adolescent; D000328:Adult; D001827:Body Height / Q000187:drug effects / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D044127:Epigenesis, Genetic; D005260:Female; D005838:Genotype; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D009154:Mutation; D011994:Recombinant Proteins / Q000008:administration & dosage; D056730:Silver-Russell Syndrome / Q000188:drug therapy / Q000235:genetics
C035170:IGF2 protein, human; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007335:Insulin-Like Growth Factor II