The purpose of this study is to elucidate the genetic causes and phenotypic presentation of nonfamilial tall stature (nFTS) and to compare these findings with those of familial tall stature (FTS) from the same population that was previously studied. Children with nFTS (defined as a height > + 2 SDs with both parents' heights < + 2 SDs) underwent endocrine and anthropometric examinations and genetic testing (karyotyping, SHOX gene dosage analysis and next-generation sequencing of 786 growth-associated genes). Exome sequencing was performed in patients with negative genetic results and a height > + 3 SDs. A total of 55 children with nFTS were enrolled. The median height was + 2.8 SD (2.4-3.2 SD), and the median midparental height was + 0.7 SD (0.4-0.9 SD). Genetic causes of tall stature were identified in 6/55 (11%) children. Specifically, four children had gonosomal aneuploidy (47,XXY [2x], 47,XXX, 48,XXXX), one had a heterozygous complex rearrangement including SHOX gene duplication, and one carried a pathogenic variant in the TGFBR2 gene leading to Loeys-Dietz syndrome. A genetic cause of tall stature was significantly less common in nFTS (11%) than in our previously published cohort with FTS (32%). Conclusion: Cytogenetic abnormalities were the predominant genetic alteration identified in children with nFTS, confirming the justification of karyotype analysis in this cohort. The probability of genetic alterations was greater in children with FTS than in those with nFTS. Our findings suggest that the current guidelines for complex investigation are efficient for children with nFTS but need revision in children with FTS. What is known - what is new • Although tall stature is generally considered beneficial, it can be associated with health risks which need to be recognized in time. Tall stature without intellectual impairment is usually considered to be polygenic. • However, the cause of familial tall stature was monogenic more often than it was thought previously. • Children with non-familial and apparently non-syndromic tall stature have never been systematically investigated. • Monogenic causes of non-familial tall stature were observed in 11% of patients, including a participant with Loeys-Dietz syndrome.

• Keywords
• Genetics of tall stature, Growth, Next-generation sequencing, Non-familial tall stature, Tall stature,
• MeSH
• Chromosome Aberrations * MeSH
• Child MeSH
• Phenotype MeSH
• Genetic Testing MeSH
• Karyotyping MeSH
• Humans MeSH
• Adolescent MeSH
• Growth Disorders * genetics   MeSH
• Child, Preschool MeSH
• Short Stature Homeobox Protein MeSH
• Exome Sequencing MeSH
• Body Height * genetics   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Short Stature Homeobox Protein MeSH
• SHOX protein, human MeSH Browser

BACKGROUND: Many studies have demonstrated the association between low birth weight (LBW) and chronic kidney disease, estimated glomerular filtration rate (eGFR) and kidney volume (KV). However, studies on twins and those investigating numerous perinatal factors beyond LBW, and their associations with various kidney parameters are scarce. METHODS: A two-center cross-sectional study on five-year-old LBW children was conducted between 2021 and 2023. 110 children were enrolled (8 LBW, 58 very LBW (VLBW), 44 extremely LBW (ELBW)); 56 were twins. We examined associations between birth weight (BW), various prenatal, perinatal and postnatal factors, and eGFR, KV, tubular abnormalities and kidney ultrasound abnormalities, both in singletons and twins. RESULTS: In children with ELBW, eGFR correlated with BW (r = 0.55, P = 0.0018), while in those with BW ≥ 1000 g, eGFR remained constant. Other factors associated with decreased eGFR were hypertensive disorder of pregnancy (93.86 vs. 87.26 ml/min/1.73m2, P = 0.0285) in singletons, decreased growth velocity (β = 0.83, P = 0.0277) in twins, and lower total KV (tKV) and relative KV (rKV) in both singletons (r = 0.60, P < 0.0001 for tKV and r = 0.45, P = 0.0010 for rKV) and twins (β = 0.34, P < 0.0001 for tKV and β = 0.23, P = 0.0002 for rKV). Based on the multivariable models excluding KV, BW and gestational age were associated with eGFR in singletons, while male gender, BW, growth velocity, and coffee drinking during pregnancy were associated with eGFR in twins. However, in models that included KV, BW, gestational age and growth velocity were no longer significant. Total KV was associated with BW (r = 0.39, P = 0.0050 for singletons; β = 2.85, P < 0.0001 for twins), body mass index (r = 0.34, P = 0.0145 for singletons; β = 8.44, P < 0.0001 for twins), and growth velocity (β = 1.43, P = 0.0078). Twins born small for gestational age had lower tKV (70.88 vs 89.20 ml, P < 0.0001). Relative KV showed similar associations. Relative kidney volumes were significantly lower for both kidneys compared to the reference population (55.02 vs 65.42 ml/m2, P < 0.0001 for right kidney and 61.12 vs 66.25 ml/m2, P = 0.0015 for left kidney); however, only 8.6% of children had rKV below 10th percentile. CONCLUSION: Many factors affect eGFR and KV, some of them differ between twins and singletons. Based on multivariable models, eGFR seems to be better predicted by KV than by BW and gestational age in LBW children. Relative kidney volumes were significantly lower in our cohort compared to the reference population, but only 8.6% of rKV were below 10th percentile.

• Keywords
• 5-year-old children, Glomerular filtration rate, Kidney volume, Low birth weight, Prematurity, Twins,
• MeSH
• Renal Insufficiency, Chronic * physiopathology   epidemiology   etiology   MeSH
• Twins MeSH
• Glomerular Filtration Rate MeSH
• Kidney * diagnostic imaging   physiopathology   pathology   MeSH
• Humans MeSH
• Infant, Low Birth Weight * MeSH
• Infant, Newborn MeSH
• Birth Weight MeSH
• Child, Preschool MeSH
• Cross-Sectional Studies MeSH
• Pregnancy MeSH
• Organ Size MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Twin Study MeSH

Because the causes of combined pituitary hormone deficiency (CPHD) are complex, the etiology of congenital CPHD remains unknown in most cases. The aim of the study was to identify the genetic etiology of CPHD in a well-defined single-center cohort. In total, 34 children (12 girls) with congenital CPHD (growth hormone (GH) deficiency and impaired secretion of at least one other pituitary hormone) treated with GH in our center were enrolled in the study. Their median age was 11.2 years, pre-treatment height was -3.2 s.d., and maximal stimulated GH was 1.4 ug/L. Of them, 30 had central adrenal insufficiency, 27 had central hypothyroidism, ten had hypogonadotropic hypogonadism, and three had central diabetes insipidus. Twenty-six children had a midline defect on MRI. Children with clinical suspicion of a specific genetic disorder underwent genetic examination of the gene(s) of interest via Sanger sequencing or array comparative genomic hybridization. Children without a detected causal variant after the first-tier testing or with no suspicion of a specific genetic disorder were subsequently examined using next-generation sequencing growth panel. Variants were evaluated by the American College of Medical Genetics standards. Genetic etiology was confirmed in 7/34 (21%) children. Chromosomal aberrations were found in one child (14q microdeletion involving the OTX2 gene). The remaining 6 children had causative genetic variants in the GLI2, PROP1, POU1F1, TBX3, PMM2, and GNAO1 genes, respectively. We elucidated the cause of CPHD in a fifth of the patients. Moreover, our study supports the PMM2 gene as a candidate gene for CPHD and suggests pathogenic variants in the GNAO1 gene as a potential novel genetic cause of CPHD.

• Keywords
• combined pituitary hormone deficiency, genetics of short stature, growth hormone deficiency, next-generation sequencing, short stature,
• Publication type
• Journal Article MeSH

The rising prevalence of obesity in children calls for new strategies for the provision of effective care by a multidisciplinary team. Telemedicine has overall proven to be an effective tool for promoting a healthy lifestyle. The main objective of the current paper is to present the protocol of our ongoing CardioMetabolic Prevention (CAMP) study and compare its design with published studies on telemedicine in paediatric obesity. Additionally, we analysed the preliminary anthropometric and laboratory data to test the efficacy of our 12-week intensive program that combines in-person and telemedicine support. The program demonstrated a positive impact on body mass index (BMI) and its z-scores in 21 adolescents, and BMI in 18 participating parents. However, we found no effect on body composition, waist circumference, cardiometabolic parameters, or fitness evaluated via a 6-min walk test in adolescents. In conclusion, the combination of in-person and telemedicine intensive support over 35 h delivered by a multidisciplinary team can be beneficial not only for adolescents with obesity but also for their parents. The ongoing CAMP study serves as a platform for precision medicine in future decisions regarding anti-obesity medication in adolescents with obesity.

• Keywords
• adolescents, cardiometabolic prevention, healthy lifestyle support, mental health, obesity, parental involvement, telemedicine, weight reduction,
• Publication type
• Journal Article MeSH

Familial short stature (FSS) describes vertically transmitted growth disorders. Traditionally, polygenic inheritance is presumed, but monogenic inheritance seems to occur more frequently than expected. Clinical predictors of monogenic FSS have not been elucidated. The aim of the study was to identify the monogenic etiology and its clinical predictors in FSS children. Of 747 patients treated with growth hormone (GH) in our center, 95 with FSS met the inclusion criteria (pretreatment height ≤-2 SD in child and his/her shorter parent); secondary short stature and Turner/Prader-Willi syndrome were excluded criteria. Genetic etiology was known in 11/95 children before the study, remaining 84 were examined by next-generation sequencing. The results were evaluated by American College of Medical Genetics and Genomics (ACMG) guidelines. Nonparametric tests evaluated differences between monogenic and non-monogenic FSS, an ROC curve estimated quantitative cutoffs for the predictors. Monogenic FSS was confirmed in 36/95 (38%) children. Of these, 29 (81%) carried a causative genetic variant affecting the growth plate, 4 (11%) a variant affecting GH-insulin-like growth factor 1 (IGF1) axis and 3 (8%) a variant in miscellaneous genes. Lower shorter parent's height (P = 0.015) and less delayed bone age (BA) before GH treatment (P = 0.026) predicted monogenic FSS. In children with BA delayed less than 0.4 years and with shorter parent's heights ≤-2.4 SD, monogenic FSS was revealed in 13/16 (81%) cases. To conclude, in FSS children treated with GH, a monogenic etiology is frequent, and gene variants affecting the growth plate are the most common. Shorter parent's height and BA are clinical predictors of monogenic FSS.

• Keywords
• GH treatment, familial short stature, growth plate disorders, next-generation sequencing, predictors of monogenic short stature,
• Publication type
• Journal Article MeSH

The fatty acid composition is associated with obesity. Omega 3 polyunsaturated fatty acid (PUFA) could have a beneficial role in the prevention and treatment of many disorders, including cardiometabolic diseases. A cohort of 84 men and 131 women were examined in adolescence and after 8 years. Body weight (BW) and fat mass (FM) were measured. The composition of fatty acids (FAs) of serum phospholipids was assessed using gas chromatography. Statistics: PLS method. Aim: to determine the relationships between FAs in adolescence and FM (explanatory variable 1, EV1) and BW (explanatory variable 2, EV2) in adulthood. In the predictive models, a cluster of FAs in boys explained 47.2 % of EV1 and a cluster of 6 FAs in girls explained 32.3 % of EV1 measured in adulthood. FAs measured in adolescents explained 23.7 % of EV2 in early adults regardless of gender. A significant negative association was found between 18:1n-9c and EV1 in males and EV2 in both genders. We found a significant negative association between 18:2n-6 and 20:0 and both EV1 and EV2. In all analyses, we found a significant negative association of 20:1n-9 and 18:3n-3 with EV1-2 in both genders. A significant positive association was found in 20:3n-6 with EV1 and EV2 in males. 20:4n-6 was positively associated with EV1 in females and EV2 in both genders. A positive association between FM and very long chain n- 6 PUFAs was also observed. It is concluded that serum MUFAs and essential PUFAs in adolescence are associated with lower BW and FM in adulthood.

• MeSH
• Adult MeSH
• Phospholipids MeSH
• Humans MeSH
• Fatty Acids * MeSH
• Adolescent MeSH
• Follow-Up Studies MeSH
• Fatty Acids, Unsaturated MeSH
• Fatty Acids, Omega-3 * MeSH
• Body Composition MeSH
• Body Weight MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Phospholipids MeSH
• Fatty Acids * MeSH
• Fatty Acids, Unsaturated MeSH
• Fatty Acids, Omega-3 * MeSH

INTRODUCTION: The growth hormone deficiency (GHD) diagnosis is controversial especially due to low specificity of growth hormone (GH) stimulation tests. It is therefore believed that children diagnosed with GHD form a heterogeneous group with growth disorder frequently independent on GH function. No study evaluating the complex etiology of growth failure in children with diagnosed GHD has been performed thus far. AIMS: To discover genetic etiology of short stature in children with diagnosed GHD from families with short stature. METHODS: Fifty-two children diagnosed with primary GHD and vertically transmitted short stature (height SDS in the child and his/her shorter parent <-2 SD) were included to our study. The GHD diagnosis was based on growth data suggestive of GHD, absence of substantial disproportionality (sitting height to total height ratio <-2 SD or >+2 SD), IGF-1 levels <0 for age and sex specific SD and peak GH concentration <10 ug/L in two stimulation tests. All children were examined using next-generation sequencing methods, and the genetic variants were subsequently evaluated by American College of Medical Genetics standards and guidelines. RESULTS: The age of children at enrollment into the study was 11 years (median, IQR 9-14 years), their height prior to GH treatment was -3.0 SD (-3.6 to -2.8 SD), IGF-1 concentration -1.4 SD (-2.0 to -1.1 SD), and maximal stimulated GH 6.3 ug/L (4.8-7.6 ug/L). No child had multiple pituitary hormone deficiency or a midbrain region pathology. Causative variant in a gene that affects growth was discovered in 15/52 (29%) children. Of them, only 2 (13%) had a genetic variant affecting GH secretion or function (GHSR and OTX2). Interestingly, in 10 (67%) children we discovered a primary growth plate disorder (ACAN, COL1A2, COL11A1, COL2A1, EXT2, FGFR3, NF1, NPR2, PTPN11 [2x]), in one (7%) a genetic variant impairing IGF-1 action (IGFALS) and in two (12%) a variant in miscellaneous genes (SALL4, MBTPS2). CONCLUSIONS: In children with vertically transmitted short stature, genetic results frequently did not correspond with the clinical diagnosis of GH deficiency. These results underline the doubtful reliability of methods standardly used to diagnose GH deficiency.

• Keywords
• genetics, growth hormone, growth hormone deficiency, next-generation sequencing, short stature,
• MeSH
• Child MeSH
• Dwarfism, Pituitary * diagnosis   genetics   drug therapy   MeSH
• Insulin-Like Growth Factor I genetics   MeSH
• Humans MeSH
• Human Growth Hormone * MeSH
• Adolescent MeSH
• Reproducibility of Results MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Insulin-Like Growth Factor I MeSH
• Human Growth Hormone * MeSH

AIMS/HYPOTHESIS: The proportion of children with type 1 diabetes (T1D) who have experience with low-carbohydrate diet (LCD) is unknown. Our goal was to map the frequency of LCD among children with T1D and to describe their clinical and laboratory data. METHODS: Caregivers of 1040 children with T1D from three centers were addressed with a structured questionnaire regarding the children's carbohydrate intake and experience with LCD (daily energy intake from carbohydrates below 26% of age-recommended values). The subjects currently on LCD were compared to a group of non-LCD respondents matched to age, T1D duration, sex, type and center of treatment. RESULTS: A total of 624/1040 (60%) of the subjects completed the survey. A total of 242/624 (39%) subjects reported experience with voluntary carbohydrate restriction with 36/624 (5.8%) subjects currently following the LCD. The LCD group had similar HbA1c (45 vs. 49.5, p = 0.11), lower average glycemia (7.0 vs. 7.9, p = 0.02), higher time in range (74 vs. 67%, p = 0.02), lower time in hyperglycemia >10 mmol/L (17 vs. 20%, p = 0.04), tendency to more time in hypoglycemia <3.9 mmol/L(8 vs. 5%, p = 0.05) and lower systolic blood pressure percentile (43 vs. 74, p = 0.03). The groups did not differ in their lipid profile nor in current body height, weight or BMI. The LCD was mostly initiated by the parents or the subjects themselves and only 39% of the families consulted their decision with the diabetologist. CONCLUSIONS/INTERPRETATION: Low carbohydrate diet is not scarce in children with T1D and is associated with modestly better disease control. At the same time, caution should be applied as it showed a tendency toward more frequent hypoglycemia.

• Keywords
• low-carbohydrate diet, time in range, type 1 diabetes,
• MeSH
• Diabetes Mellitus, Type 1 diet therapy   metabolism   MeSH
• Diet, Carbohydrate-Restricted * adverse effects   statistics & numerical data   MeSH
• Child MeSH
• Glycated Hemoglobin analysis   MeSH
• Body Mass Index MeSH
• Blood Glucose analysis   MeSH
• Humans MeSH
• Lipids blood   MeSH
• Surveys and Questionnaires MeSH
• Body Weight MeSH
• Body Height MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Names of Substances
• Glycated Hemoglobin A MeSH
• Blood Glucose MeSH
• Lipids MeSH

Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD/MTPD) and medium chain acyl-CoA dehydrogenase deficiency (MCADD) were included in the expanded neonatal screening program (ENBS) in Czechia in 2009, allowing for the presymptomatic diagnosis and nutritional management of these patients. The aim of our study was to assess the nationwide impact of ENBS on clinical outcome. This retrospective study analysed acute events and chronic complications and their severity in pre-ENBS and post-ENBS cohorts. In total, 28 children (12 before, 16 after ENBS) were diagnosed with LCHADD/MTPD (incidence 0.8/100,000 before and 1.2/100,000 after ENBS). In the subgroup detected by ENBS, a significantly longer interval from birth to first acute encephalopathy was observed. In addition, improvement in neuropathy and cardiomyopathy (although statistically non-significant) was demonstrated in the post-ENBS subgroup. In the MCADD cohort, we included 69 patients (15 before, 54 after ENBS). The estimated incidence rose from 0.7/100,000 before to 4.3/100,000 after ENBS. We confirmed a significant decrease in the number of episodes of acute encephalopathy and lower proportion of intellectual disability after ENBS (p < 0.0001). The genotype-phenotype correlations suggest a new association between homozygosity for the c.1528C > G variant and more severe heart involvement in LCHADD patients.

• Keywords
• clinical outcome, fatty acid oxidation disorders, neonatal screening program, severity assessment,
• MeSH
• 3-Hydroxyacyl CoA Dehydrogenases deficiency   MeSH
• Acyl-CoA Dehydrogenase deficiency   MeSH
• Child MeSH
• Outcome Assessment, Health Care MeSH
• Incidence MeSH
• Cardiomyopathies diagnosis   diet therapy   epidemiology   MeSH
• Carnitine analogs & derivatives   blood   MeSH
• Infant MeSH
• Humans MeSH
• Mitochondrial Myopathies diagnosis   diet therapy   epidemiology   MeSH
• Mitochondrial Trifunctional Protein deficiency   MeSH
• Nervous System Diseases diagnosis   diet therapy   epidemiology   MeSH
• Infant, Newborn MeSH
• Neonatal Screening methods   MeSH
• Child, Preschool MeSH
• Retrospective Studies MeSH
• Rhabdomyolysis diagnosis   diet therapy   epidemiology   MeSH
• Severity of Illness Index MeSH
• Lipid Metabolism, Inborn Errors diagnosis   diet therapy   epidemiology   MeSH
• Metabolism, Inborn Errors diagnosis   MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• 3-Hydroxyacyl CoA Dehydrogenases MeSH
• Acyl-CoA Dehydrogenase MeSH
• acylcarnitine MeSH Browser
• Carnitine MeSH
• Mitochondrial Trifunctional Protein MeSH

BACKGROUND: Isolated nocturnal hypertension (INH) is associated with increased prevalence of left ventricular hypertrophy (LVH) and cardiovascular morbidity and mortality in adult patients. Unlike in adults, data illustrating the possible association between INH and cardiac target organ damage is lacking in children. This study aimed to investigate whether INH is associated with increased left ventricular mass index (LVMI) and LVH in children. METHODS: Retrospective data from all untreated children with confirmed ambulatory hypertension (HT) in our center was reviewed. Ambulatory blood pressure monitoring (ABPM) and echocardiography were performed concurrently. Ambulatory normotensive children served as controls. LVH was defined as LVMI ≥ 95th percentile. RESULTS: There were 102 ABPM studies; of these, 79 children had renal HT, and 23 had primary HT. Median age of children was 13.2 years (3.8-18.9). Nineteen children had INH, 9 children had isolated daytime HT, 54 had daytime and nighttime HT, and 20 were normotensive. The LVMI adjusted for age (patient's LVMI/95th percentile of the LVMI) was significantly higher in children with INH than in normotensive children (0.83 ± 0.03 vs. 0.74 ± 0.03, p = 0.03). Left ventricular hypertrophy was present in 11% of children with INH; this was not significantly higher than in normotensive children (0%, p = 0.23). CONCLUSIONS: This study investigated the association between INH and cardiac structure in children with primary and renal HT and showed children with INH had higher LVMI adjusted for age than normotensive children and children with INH had similar LVMI adjusted for age to children with isolated daytime HT.

• Keywords
• Ambulatory blood pressure monitoring, Children, Echocardiography, Isolated nocturnal hypertension, LVMI, Left ventricular hypertrophy,
• MeSH
• Blood Pressure Monitoring, Ambulatory * MeSH
• Child MeSH
• Hypertension * complications   epidemiology   MeSH
• Hypertrophy, Left Ventricular diagnostic imaging   epidemiology   MeSH
• Blood Pressure MeSH
• Humans MeSH
• Adolescent MeSH
• Child, Preschool MeSH
• Retrospective Studies MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Child, Preschool MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH