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.

Population-based references for waist and hip circumferences, waist-to-hip and waist-to-height ratios for children and adolescents, and evaluation of their predictive ability.

Childhood obesity is a public health problem globally as well as in Poland. This paper aimed to provide age- and sex-specific waist circumference, hip circumference, waist-to-height ratio and waist-to-hip ratio normative values for Polish children and adolescents aged 3 - 18 years for more precise monitoring of abdominal fat accumulation. The waist circumference, hip circumference, waist-to-height ratio and waist-to-hip ratio references were constructed with the lambda-mu-sigma (LMS) method using data from two nationally representative health surveys: the OLA study and the OLAF study, the largest available paediatric surveys in Poland which provided measured height, weight, waist, hip and blood pressure for 22,370 children and adolescents aged 3 - 18 years. The predictive ability of newly established references for overweight/obesity as defined by the International Obesity Task Force criteria and elevated blood pressure was tested with receiver operating characteristic. Abdominal obesity cut-offs linked to adult cardiometabolic cut-offs were established. Reference values for waist circumference, hip circumference, waist-to-height ratio and waist-to-hip ratio are presented, as well as waist circumference, waist-to-height ratio and waist-to-hip ratio cut-off values linked to adult's cut-offs of cardiometabolic risk. The predictive value for overweight and obesity of population-based waist, hip and waist-to-height ratio references was outstanding-area under the receiver operating characteristic curve > 0.95 in both sexes, whereas with regard to the elevated blood pressure predictive ability was low-area under the receiver operating characteristic curve < 0.65.   Conclusion: This paper presents the first waist, hip, waist-to-height ratio and waist-to-hip ratio references for Polish children and adolescents aged 3-18 years. The 90th and 95th percentile and cut-offs linked to adult thresholds for cardiometabolic risk are proposed as cut-offs for abdominal obesity. What is Known: • Waist circumference, waist-to-height ratio and waist-to-hip ratio are used to assess abdominal obesity in children and adults. • In Poland, there is no abdominal obesity and hip circumference references for children and adolescents from 3 to 18 years of age. What is New: • Population-based references of central obesity indices and hip references for children and youth aged 3-18 years and cardiometabolic risk thresholds for children and adolescents linked to adult's cut-offs were established.

Prospective BMI changes in preschool children are associated with parental characteristics and body weight perceptions: the ToyBox-study.

OBJECTIVE: To examine the effect of the intervention implemented in the ToyBox-study on changes observed in age- and sex-specific BMI percentile and investigate the role of perinatal factors, parental perceptions and characteristics on this change. DESIGN: A multicomponent, kindergarten-based, family-involved intervention with a cluster-randomised design. A standardised protocol was used to measure children's body weight and height. Information was also collected from parents/caregivers via the use of validated questionnaires. Linear mixed effect models with random intercept for country, socio-economic status and school were used. SETTING: Selected preschools within the provinces of Oost-Flanders and West-Flanders (Belgium), Varna (Bulgaria), Bavaria (Germany), Attica (Greece), Mazowieckie (Poland) and Zaragoza (Spain). PARTICIPANTS: A sample of 6268 preschoolers aged 3·5-5·5 years (51·9 % boys). RESULTS: There was no intervention effect on the change in children's BMI percentile. However, parents' underestimation of their children's actual weight status, parental overweight and mothers' pre-pregnancy overweight/obesity were found to be significantly and independently associated with increases in children's BMI percentile in multivariate modelling. CONCLUSIONS: As part of a wide public health initiative or as part of a counseling intervention programme, it is important to assist parents/caregivers to correctly perceive their own and their children's weight status. Recognition of excessive weight by parents/caregivers can increase their readiness to change and as such facilitate higher adherence to favourable behavioural changes within the family.

International Waist Circumference Percentile Cutoffs for Central Obesity in Children and Adolescents Aged 6 to 18 Years.

CONTEXT: No universal waist circumference (WC) percentile cutoffs used have been proposed for screening central obesity in children and adolescents. OBJECTIVE: To develop international WC percentile cutoffs for children and adolescents with normal weight based on data from 8 countries in different global regions and to examine the relation with cardiovascular risk. DESIGN AND SETTING: We used pooled data on WC in 113,453 children and adolescents (males 50.2%) aged 4 to 20 years from 8 countries in different regions (Bulgaria, China, Iran, Korea, Malaysia, Poland, Seychelles, and Switzerland). We calculated WC percentile cutoffs in samples including or excluding children with obesity, overweight, or underweight. WC percentiles were generated using the general additive model for location, scale, and shape (GAMLSS). We also estimated the predictive power of the WC 90th percentile cutoffs to predict cardiovascular risk using receiver operator characteristics curve analysis based on data from 3 countries that had available data (China, Iran, and Korea). We also examined which WC percentiles linked with WC cutoffs for central obesity in adults (at age of 18 years). MAIN OUTCOME MEASURE: WC measured based on recommendation by the World Health Organization. RESULTS: We validated the performance of the age- and sex-specific 90th percentile WC cutoffs calculated in children and adolescents (6-18 years of age) with normal weight (excluding youth with obesity, overweight, or underweight) by linking the percentile with cardiovascular risk (area under the curve [AUC]: 0.69 for boys; 0.63 for girls). In addition, WC percentile among normal weight children linked relatively well with established WC cutoffs for central obesity in adults (eg, AUC in US adolescents: 0.71 for boys; 0.68 for girls). CONCLUSION: The international WC cutoffs developed in this study could be useful to screen central obesity in children and adolescents aged 6 to 18 years and allow direct comparison of WC distributions between populations and over time.

Clinical and molecular genetic characterization of a male patient with Sensenbrenner syndrome (cranioectodermal dysplasia) and biallelic WDR35 mutations.

BACKGROUND: Sensenbrenner syndrome (cranioectodermal dysplasia, CED) is a very rare autosomal recessive ciliopathy first described by Judith Sensenbrenner in 1975. CED is a complex disorder characterized by craniofacial, skeletal, and ectodermal abnormalities. The clinical symptoms are variable and the CED phenotype may present intrafamilial and interfamilial differences. Sensenbrenner syndrome belongs to a group of ciliary chondrodysplasias and is a genetically heterogeneous disease. Mutations in six genes: IFT122, WDR35, IFT43, WDR19, IFT52, and IFT140 have been associated with this disorder. All known CED genes encode proteins that are part of the intraflagellar transport complex, which plays an important role in the assembly and maintenance of cilia. CASE: We report a on 2-year-old male patient affected by Sensenbrenner syndrome. Dysmorphic features included short stature with rhizomelic shortening of limbs, short fingers, narrow chest, high forehead, epicanthal folds, telecanthus, broad nasal bridge, low-set ears, sparse hair, and widely space teeth. Craniosynostosis was surgically corrected at the age of 4 months. The patient presented chronic renal disease. Nephrologic picture showed early stages of nephronophthisis. Psychomotor development was apparently normal. Molecular analysis of the affected individual revealed compound heterozygosity for a novel nonsense p.(Arg113*) and a missense p.(Asp841Val) variant in the WDR35 gene. CONCLUSIONS: The observations of the CED patient in this study provide additional clinical data and expand the molecular spectrum of Sensenbrenner syndrome. Moreover, the two variants identified in the proband provide further evidence for the WDR35 mutations as the most common cause of this rare syndrome.

Intrafamilial phenotypic variability in a Polish family with Sensenbrenner syndrome and biallelic WDR35 mutations.

Sensenbrenner syndrome (cranioectodermal dysplasia, CED) is a very rare autosomal recessive ciliopathy. Cranioectodermal dysplasia is characterized by craniofacial, skeletal, and ectodermal abnormalities. About 50 patients have been described to date. Sensenbrenner syndrome belongs to a group of ciliary chondrodysplasias and is a genetically heterogeneous disorder. Mutations in five genes: IFT122, WDR35, IFT43, WDR19, and IFT52 have been associated with CED. All known genes encode proteins that are part of the intraflagellar transport complex, which plays an important role in the assembly and maintenance of cilia. Here, we report a family with two children affected by Sensenbrenner syndrome, a 9-year-old girl and her older sister who died in infancy due to respiratory, liver, and renal insufficiency. Dysmorphic features included short stature with rhizomelic shortening of limbs, short fingers, preaxial polydactyly of left hand, narrow chest, craniosynostosis, dolichocephaly, high anterior hairline, epicanthal folds and telecanthus, depressed nasal bridge, low-set ears, and additional ectodermal abnormalities. The patient presented with chronic tubulointerstitial renal disease. She had abnormal echogenicity on renal ultrasound, reduced glomerular filtration, albuminuria and tubular proteinuria, hypocalciuria and hypocitraturia, accompanied by pre-hypertensive state. This pattern of renal abnormality was regarded as nephronophthisis. Psychomotor development was apparently normal. Molecular analysis in one of the affected individuals identified compound heterozygosity for a nonsense (c.1922T>G, p.(Leu641*)) and missense (c.2522A>T, p.(Asp841Val)) variants in WDR35. We present a detailed clinical descriptions of two female siblings showing an intrafamilial phenotypic variability of the disease, and illustrating the potential lethality of CED.