The effects of 3-year growth hormone treatment and body composition in Polish patients with Silver-Russell syndrome.

INTRODUCTION: Silver-Russell syndrome (SRS) is characterized by clinical and genetic heterogeneity. SRS is the only disease entity associated with (epi)genetic abnormalities of 2 different chromosomes: 7 and 11. In SRS, the 2 most frequent molecular abnormalities are hypomethylation (loss of methylation) of region H19/IGF2:IG-DMR on chromosome 11p15.5 (11p15 LOM) and maternal uniparental disomy of chromosome 7 (upd(7)mat). Therapy with recombinant human growth hormone (rhGH) is implemented to increase body height in children with SRS. The effect of the administered rhGH on height, weight, body mass index (BMI), body composition, and height velocity in patients with SRS during 3 years of rhGH therapy was analysed. MATERIAL AND METHODS: 31 SRS patients (23 with 11p15 LOM, 8 with upd(7)mat) and 16 patients small for gestational age (SGA) as a control group were diagnosed and followed up in The Children's Memorial Health Institute. Patients were eligible for the 2 Polish rhGH treatment programmes [for patients with SGA or with growth hormone deficiency (GHD)]. Anthropometric parameters were collected in all patients. Body composition using bioelectrical impedance was measured in 13 SRS and 14 SGA patients. RESULTS: Height, weight, and weight for height (SDS) at baseline of rhGH therapy were lower in SRS patients than in the SGA control group: -3.3 ± 1.2 vs. -2.6 ± 06 (p = 0.012), -2.5 vs. -1.9 (p = 0.037), -1.7 vs. -1.1 (p = 0.038), respectively. Height SDS was increased from -3.3 ± 1.2 to -1.8 ± 1.0 and from -2.6 ± 0.6 to -1.3 ± 0.7 in the SRS and SGA groups, respectively. Patients with 11p15 LOM and upd(7) mat achieved similar height, 127.0 ± 15.7 vs. 128.9 ± 21.6 cm, and -2.0 ± 1.3 vs. -1.7 ± 1.0 SDS, respectively. Fat mass percentage decreased in SRS patients from 4.2% to 3.0% (p < 0.05) and in SGA patients from 7.6% to 6.6% (p < 0.05). CONCLUSIONS: Growth hormone therapy has a positive influence on the growth of SRS patients. Regardless of molecular abnormality type (11p15 LOM vs. upd(7)mat), height velocity was similar in SRS patients during 3 years of rhGH therapy.

Assessment of insulin resistance in preterm children appropriate for gestational age versus term and preterm children with intrauterine growth restriction.

INTRODUCTION: Estimation of carbohydrate metabolism parameters in the groups: AGA preterm, SGA term, SGA preterm and AGA term. MATERIAL AND METHODS: 89 children were qualified: group A - AGA preterm 22, group B - SGA preterm 26, SGA term group C - 30 children, AGA - term group D - 11 children; at the age of 6-7 years. Insulin and fasting glucose levels were measure. HOMA IR and QUICKI, lipid profile were calculated. RESULTS: Higher insulin concentration were found in groups C vs. A (6.93 vs. 3.68 uIU/ml, p = 0.00005); B vs A (5.49 vs. 3.68 uIU/ml, p = 0.02). HOMA IR was significantly higher in the C vs A group (1.38 vs. 0.73, p = 0.00014); and B vs A (1.11 vs. 0.73, p = 0.03). Quicki were lower in C vs. A (0.7 vs. 0.96, p = 0.00068). CONCLUSIONS: The risk of insulin resistance appears to be more associated with lower birth weight than time of birth. No greater risk of insulin resistance has been established in preterm births with AGA.

What's new in IUGR from the endocrinological point of view?

Genetic causes of IUGR: The IGF 2 gene encoding IGF2 synthesis contributes to growth of the foetus. The maternal genes PHLDA2, GRB10, and placental ALS also play a role in the regulation of foetal growth. CDKN1C mutation can lead to IUGR. In SRS syndrome, apart from epimutation 11p15 and disomy 7, the cause may be a mutation of HMAGA2-PLAG1-IGF2 genes. Growth deficiency: in 10% of children with IUGR with growth deficiency, ACAN gene mutation (aggrecan gene) was described. Children with IUGR and with dynamic evolution of puberty can achieve better final growth through combined therapy with GH and GnRH analogues. Insulin resistance: In light of new reports, oxidative stress during pregnancy, epigenetic regulation in the foetal period in children with IUGR, and insulin resistance both peripheral and central during catch up growth" are observed.

The effects of growth hormone therapy on the somatic development of a group of Polish children with Silver-Russell syndrome.

OBJECTIVE: Silver-Russell Syndrome is both clinically and genetically a heterogeneous syndrome. Among the most important dysmorphic features of this condition are: a triangular shaped face with a small mandible, a prominent frontal eminence, a thin vermilion border with downward-pointing lip corners, clino- and brachydactyly of the 5th fingers as well as body asymmetry. The most well-known genetic mutations in this syndrome are: the 11p15 epimutation (20-60% patients) and the maternal uniparental chromosome 7 disomy present in 7% to 15% of patients. Children with SRS have severely impaired physical growth - intrauterine and after birth. This, together with the aforementioned dysmorphic features, forms the main diagnostic criteria. MATERIAL AND METHODS: The study group consisted of 12 children treated with growth hormone, aged 2 to 17 (8.9±4.0 years), therein, all of whom met the phenotype diagnostic criteria by Wollmann and Price. The effects of growth hormone therapy on somatic development of these children are also presented. RESULTS: Height and weight improved as a result of growth hormone treatment, but the effects were significantly worse than in children with IUGR. Children from the study group presented also a smaller an improvement in growth velocity than children from the control group, but the difference was statistically insignificant. CONCLUSIONS: Growth hormone therapy accelerates the growth of children with SRS but to a smaller extent than the growth of children born with intrauterine growth retardation without dysmorphic features.

A ten-year observation of somatic development of a first group of Polish children with Silver-Russell syndrome.

OBJECTIVE: Silver-Russell syndrome is heterogeneous both clinically and genetically. The best known genetic aberrations existing in this syndrome are an 11p15 epimutation, present in 20-60% patients, and a maternal uniparental chromosome 7 disomy (7-15%) (upd(7)mat). Children with SRS suffer from physical growth impairments - intrauterine and after birth. MATERIAL AND METHODS: The study group consisted of 38 children aged 2 to 17 (x=8.9 ± 4.0 years). These children had undergone a genetic analysis in search for the 11p15 epimutation and the upd(7)mat. Somatic growth was also analysed in terms of birth parameters and postnatal BMI, weight and height. The aforementioned parameters were compared in a subgroup of children with the genetic aberrations and with a control group of children born with IUGR. RESULTS: In the study group a mean weight SD on birth was -3.41 ± 1.22, the birth height was -1.25 ± 2.08 SD and a head circumference of -3.56 ± 1.93 SD. No significant differences were noted between the SRS study group and the control group in reference to weight and head circumference (p>0.05). Such difference was, however, seen in birth height. Children with 11p15 epimutation had significantly lower weight and height at birth, but a significantly larger head circumference than children without this genetic aberration. When analysing further development of children with SRS, a significantly smaller height SD, body mass and BMI was observed, compared with children from the control group. CONCLUSIONS: Children with SRS present impaired somatic development compared to children with IUGR, and these with a genetic aberration develop worse.

[Growth failure in a boy with Klinefelter syndrome and IUGR]. / Znaczny niedobór wzrostu u chlopca z zespolem Klinefeltera i hipotrofia wewnatrzmaciczna

BACKGROUND: Children born with a history of Intra-Uterine Growth Retardation (IUGR) may be susceptible for reduced growth velocity and growth deficiency. The causes of GH/IGF-1 resistance are unknown. Klinefelter syndrome is characterized by excessive growth, resulting from hypogonadism, open bone age and a prolonged growth. OBJECTIVES: The case of a 6-year-old boy with Klinefelter syndrome born with IUGR and deep growth deficiency was studied. A CASE REPORT: A 6-year-old boy with birth weight 2300 g born of term in 38 Hbd is presented. The cariotype was 47XXY. The phenotype was typical for a child with IUGR. GH in the clonidin test was 37.4 microIU/ml, IGF-1 -- 111 ng/ml. Increased IGF-1 level from 178.1 ng/ml to 360.9 ng/ml was founded in the IGF-1 generation test. CONCLUSIONS: The cause of growth deficiency in this case could be GH/IGF-1 resistance.