Background: SilverRussell syndrome (SRS; OMIM 180860) is a genetically and clinically heterogeneous low birthweight syndrome characterised by poor postnatal growth and a number of variable dysmorphic features. Small-for-gestational age infants in general have an increased risk of metabolic complications, some initially occurring in late childhood and adolescence.
Objective and hypotheses: To identify i) response to GH based on genotype and ii) development of metabolic complications whilst on GH treatment or as young adults.
Method: A cross-sectional, observational multi-centre study across England, investigating patients >5 years with clinical or genetically confirmed SRS for response to GH and evidence of insulin resistance and hypertension on baseline screening.
Results: 37 patients (18 H19; nine mUPD7 and ten clinical; 22M: 15F, mean age at assessment 11.74 years, range 5.039.1). GH treatment increased height SDS by 0.99 (0.56 S.D.) SDS after 1 year and 1.97 (1.16) SDS after 3 years; P<0.001). A significantly better response to GH treatment was seen in mUPD7 patients compared to H19 after 3 years (P0.002). BMI increased by 0.41 SDS (1.0; P0.046) on GH treatment after 3 years. No significant difference between genetic subtypes seen. Mean % fat mass (assessed by Tanita scales) was 16.3% (5.26) with no significance between pubertal and pre-pubertal individuals. Baseline fasting lipid, insulin, glucose, leptin and adiponectin levels showed no evidence of insulin resistance or impaired fasting glycaemia (n=30) and OGTT data (n=7) showed no insulin resistance. Basal blood pressure measurements showed no evidence of hypertension (diastolic and systolic measurements <90 centile). Adrenarche was seen in seven patients and central precocious puberty requiring treatment in four patients.
Conclusion: GH treatment improves height SDS and BMI SDS in SRS patients with significant difference in height SDS increase between mUPD7 and H19 after 3 years of treatment. No evidence of insulin resistance or hypertension was seen on baseline screening.
Funding: This work was supported by Child Growth Foundation and Newlife Foundation.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology