title: The degree of H19 hypomethylation in children with Silver-Russel syndrome (SRS) is not associated with the severity of phenotype and the clinical severity score (CSS).
abstract: BACKGROUND
  Hypomethylation of the imprinting control region 1 (ICR 1) at the IGF2/H19 locus on 11p15 is linked to Silver-Russel syndrome (SRS).
  
  
  RESULTS
  We tested the hypothesis that the severity of the phenotype in SRS patients is dependent on the clinical severity score (CSS) (1). Three SRS patients were clinically scored and their scores ranged between 12, 13 and 13. Two of the three SRS patients (66%) had hypomethylation of one allele.
  
  
  CONCLUSIONS
  All three patients had high CSS. Nevertheless, only two of them had hypomethylation of one H19 allele. Interestingly, two of them had ventricular septal defects, but only one had H19 hypomethylation. All children had low birth length and weight, a classic facial phenotype, haemihypertrophy (>2.5 cm thinner left arm/leg in comparison to the right one), shorter leg, and striking thinness (BMI of >16.0). One child was operated for cryptorchidismus, and the same child had elbow contracture. Two children had scoliosis. All three children were short (-3 to 5.5 SD), and treatment with GH resulted in growth on the third percentile. Since one child had no hypomethylation and two had a lower degree of hypomethylation, the higher CSS (12, 13 and 13) was not followed by a higher degree of hypomethylation of the IGF2/H19 locus.
authors.affiliation: Medical Faculty Skopje, 50 Divizija BB, 1000 Skopje, R. Macedonia.
authors.forename: Zoran S
authors.initials: ZS
authors.lastname: Gucev
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Saranac
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jancevska
authors.forename: Velibor
authors.initials: V
authors.lastname: Tasic
mesh_terms: D000293:Adolescent; D041923:Adolescent Development; D000367:Age Factors; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D019175:DNA Methylation; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D025202:Molecular Diagnostic Techniques; D010641:Phenotype; D016133:Polymerase Chain Reaction; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D012720:Severity of Illness Index; D056730:Silver-Russell Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy
chemical_list: D005819:Genetic Markers; C094335:H19 long non-coding RNA; C485621:KCNQ1OT1 long non-coding RNA, human; D024642:Potassium Channels, Voltage-Gated; D062085:RNA, Long Noncoding