title: Plasma insulin-like growth factors (IGFs), IGF-Binding proteins (IGFBPs), acid-labile subunit (ALS) and IGFBP-3 proteolysis in individuals with clinical characteristics of Sotos syndrome.
abstract: OBJECTIVE
  Sotos syndrome is an overgrowth syndrome of poorly understood aetiology. We investigated whether this syndrome is related to alterations in plasma insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), acid-labile subunit (ALS) and serum IGFBP-3 proteolysis.
  
  
  METHODS
  Based on clinical criteria, 32 patients with clinical characteristics of Sotos syndrome (median age 8.4 years, range 1.8-48.4) were categorised into three groups: typical (n = 10, group 1), dubious (n = 12, group 2) and atypical (n = 10, group 3). Blood samples were obtained from 29 patients.
  
  
  METHODS
  Plasma IGF-I, IGF-II, E-II (pro-IGF-II and E-domain fragments), IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-6 and ALS were measured by specific radioimmunoassays (RIAs). Except for E-II immunoreactivity, the concentrations were compared with those of age references, and expressed as standard deviation scores (SDS). IGFBP-3 proteolysis was assessed by incubation of serum with [125I]-IGFBP-3, followed by gel electrophoresis and was then compared with that in normal serum and third trimester pregnancy serum.
  
  
  RESULTS
  Patients in group 1 showed significantly reduced plasma levels of IGF-II (median -0.9 SDS; p = 0.01), IGFBP-4 (-0.5 SDS; p = 0.02) and IGFBP-3 (-1.0 SDS; p = 0.01). Mean IGFBP-3 proteolysis was higher than in normal standard serum (61% vs 37%; p < 0.01) but lower than in third trimester pregnancy serum (94%; p < 0.01). Plasma IGF-I showed a tendency towards low values (median -0.9 SDS; p = 0.09), IGFBP-6 and ALS a tendency towards elevated levels (median values +0.8 SDS; p = 0.07 and +2.3 SDS; p = 0.09), and IGFBP-2 was normal. The mean value of E-II immunoreactivity was 8.7 nmol/l, similar to that in pooled normal plasma (8.6 nmol/l). Plasma and serum parameters in groups 2 and 3 were similar to reference values with the exception of plasma IGFBP-3 (in groups 2 and 3 median < or = -1.1 SDS; p < or = 0.02) and ALS (in group 3 median +1.3 SDS; p < 0.01).
  
  
  CONCLUSIONS
  Patients with typical Sotos syndrome show low plasma IGF-II, IGFBP-3, IGFBP-4, and increased proteolysis of IGFBP-3 in serum. The extent to which these findings are associated with the pathophysiology of Sotos syndrome remains uncertain.
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: de Boer
authors.forename: C M
authors.initials: CM
authors.lastname: Hoogerbrugge
authors.forename: J
authors.initials: J
authors.lastname: van Doorn
authors.forename: S C
authors.initials: SC
authors.lastname: van Buul-Offers
authors.forename: M
authors.initials: M
authors.lastname: Karperien
authors.forename: J M
authors.initials: JM
authors.lastname: Wit
mesh_terms: D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005877:Gigantism / Q000097:blood*; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism*; D013002:Somatomedins / Q000378:metabolism*; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; C075944:insulin-like growth factor binding protein, acid labile subunit; D010447:Peptide Hydrolases