The Case with Short Stature and Intellectual Disability Caused by a Novel 2q12 Duplication.

Copy number variation (CNV) is a kind of malfunction of DNA polymerase to produce extra genetic material which leads to more number of repeats in genes. The CNVs have been associated with different clinical phenotypes such as learning disabilities, short stature, and intellectual disability. The chromosomal microarray analysis is an effective diagnostic method for identifying new CNVs and understanding their clinical effects. In this case report, a variation that has not been reported previously in the literature is presented. This case report will contribute to increasing the knowledge. The CNV (arr [hg19] 2q12.1q12.3 (103,368,824-107,946,062) x3) detected in the index case was also detected in her father and male sibling. Key Words: DNA, Copy number variation, Chromosomal duplication, Intellectual disabilities.

Reliability and Validity of the Turkish Version of Impact of Weight on Quality of Life for Kids.

OBJECTIVE: The Impact of Weight on Quality of Life-Kids is a self-reported weight-related quality of life measure that has been validated for children and adolescents aged between 11 and 19. Impact of Weight on Quality of Life-Kids does not have a Turkish version. The aim of this study was to explore the reliability and validity of the Impact of Weight on Quality of Life-Kids in Turkish. MATERIALS AND METHODS: The Impact of Weight on Quality of Life-Kids was translated into Turkish using Mapi Research Institute's suggested international translation technique. The psychometric evaluation included test-retest reliability, internal consistency, discriminant validity, concurrent validity, exploratory factor analysis, and confirmatory factor analysis. RESULTS: For the total score, the internal consistency of the scale (Cronbach's alpha coefficient) was 0.93. The item-total score correlation coefficients ranged from 0.178 to 0.785. The testretest coefficients were found to be 0.94 for the total score and the subscales ranged from 0.66 to 0.89 after 2 weeks. Discriminant validity analysis demonstrated that the instrument differentiated well between the obese and non-obese samples. Five variables were discovered via factor analysis that explained 66.9% of the total variation. The chi-square/degree of freedom ratio value was 3.535, the comparative fit index value was 0.834, and the value of root mean square error of approximation was 0.10, as determined by confirmatory factor analysis. CONCLUSION: Our results demonstrated the adequate reliability and validity of the Impact of Weight on Quality of Life-Kids, suggesting that this scale is a useful tool for screening Turkish children and adolescents for weight-related quality of life.

Is Office Blood Pressure Measurement Reliable in Obese Adolescents?

BACKGROUND: Although it is not reflected in the OBP measurement in obese children, ambulatory BP changes are known to occur. MH, non-dipper pattern and nocturnal hypertension have been reported to increase in obese children. On the other hand, the factors that indicate a high risk of hypertension are still unclear. The aim of our study is to especially detect masked hypertension by 24-hour BP measurement in obese adolescents and to evaluate the relationship of masked hypertension with metabolic syndrome parameters, anthropometric measurements and hepatosteatosis in these patients. METHODS: A total of 63 adolescents diagnosed with obesity were evaluated between January 2019 and December 2019. Office blood pressure was measured for all children, and all of them underwent ABPM. Patients with and without hypertension in ABPM were compared in terms of clinical and laboratory findings. RESULTS: The mean age was 14.0 ± 1.7 years, females composed 49.2% of the study population. Office blood pressure measurement revealed hypertension in 4 (6.3%) patients and prehypertension in 15 (23.8%) patients. Thirteen patients (20.9%) were diagnosed with masked hypertension, white coat hypertension was diagnosed in 3 (4.7%) patients. Abnormal ABPM patterns were found to be significantly more frequent in patients with severely obesity (with obesity: 26.4% vs severe obesity: 55.6%, p = 0.03) and patients with a higher waist circumference and waist circumference/height ratio. CONCLUSION: The prevalence of masked hypertension in obese adolescents has been found to be quite high. Therefore, we recommend ABPM in adolescents with high waist circumference/height ratio and severe obesity, even if their office blood pressure measurements are normal.

Relevance of Pituitary Gland Magnetic Resonance Imaging Results with Clinical and Laboratory Findings in Growth Hormone Deficiency.

BACKGROUND The present study investigated the relationship between detection of organic pathologies with magnetic resonance imaging of the pituitary gland, clinical and laboratory findings, and treatment response. MATERIAL AND METHODS The study included a total of 183 patients who had isolated growth hormone deficiency, received at least 1 year of treatment, returned regularly for follow-ups, and whose pituitary magnetic resonance images were available. The patients were divided into 2 groups: those with and without pathological evidence with magnetic resonance imaging. Clinical and laboratory features and treatment responses were compared between patients with and without pathological evidence with magnetic resonance imaging. RESULTS Of the 183 patients, 105 were females and 78 were males, and 114 patients (62.2%) were prepubertal and 69 patients (37.8%) were pubertal. Their mean age was 10.01±3.25 years (1-17.6 years). Pituitary images of 153 (83.6%) patients were normal. Of the patients with detected pathologies (16.4%), 19 (10,4%) had pituitary hypoplasia, 5 (2.7%) had partial empty sella, 3 (1.7%) had ectopic neurohypophysis and 3 (1.7%) had empty sella, pineal, and arachnoid cyst. A statistically significant increase was observed in the height increase rate after treatment compared to before treatment in both groups (p<0.001). However, the group with pathology had a statistically significant (p=0. 007) post-treatment increase height rate. Although in the group with pathology there was a lower L-DOPA and clonidine peak GH response, there was not any statistically significant difference between the 2 groups (p=0.051, p=0.113). Pituitary gland length was also shorter in the group with pathology compared to the group without pathology (P<0.001). CONCLUSIONS Magnetic resonance imaging is a useful tool in assessing GH deficiency pathogenesis and in predicting treatment response.

Impaired dynamic thiol/disulfide homeostasis in pubertal gynecomastia.

BACKGROUND: The aim of the study was to evaluate the dynamic thiol/disulfide homeostasis (TDH) with a new method in patients with pubertal gynecomastia and also to investigate the relationship between sex hormones. METHODS: Thiol/disulfide homeostasis, involving native thiol (SH), disulfide (SS) and total thiol (SS + SH), was evaluated between 20 adolescent boys with gynecomastia in mid-puberty and 50 healthy adolescents, who were matched for age, body mass index (BMI) and pubertal stage. The correlations of total serum testosterone (TT) and estradiol (E2) levels with the oxidative parameters were also determined. RESULTS: No significant difference was found between the total thiol, native thiol, disulfide/native thiol and disulfide/total thiol ratios of the patient and control groups. The mean disulfide concentrations, disulfide/native thiol and the disulfide/total thiol ratios were statistically significantly higher in the patient group than in the controls. A positive correlation was found between the E2 and native thiol levels, also there was a negative correlation between the E2 and disulfide levels. TT was negatively correlated with both native thiol and disulfide levels. All these did not statistically differ between the patients with unilateral and bilateral gynecomastia. CONCLUSIONS: There was an impaired thiol/disulfide homeostasis in patients with pubertal gynecomastia. According to this result, we can postulate that oxidative stress may be an etiologic factor that contributes to initiation and/or progression of gynecomastia.

Factors Influencing Frequency and Duration of Remission in Children and Adolescents Newly Diagnosed with Type 1 Diabetes.

BACKGROUND This study aimed to determine the frequency and duration of remission in children and adolescents newly diagnosed with type 1 diabetes and to investigate factors associated with these parameters. MATERIAL AND METHODS Fifty patients newly diagnosed with T1DM were followed for 1 year. Daily insulin requirement of less than 0.5 U/kg/day dose when the HbA1c value is less than 8% was regarded as partial remission. Patients were grouped according to their remission duration. Clinical and laboratory characteristics of the remission groups and non-remission groups were compared to find factors influencing remission and to investigate their contribution to the duration of remission. RESULTS Remission was observed in 24 (48%) out of 50 patients included in the study. Remission frequency was found to be associated with age, sex, and puberty. Longer duration of remission was more frequent in the younger age group, in pre-pubertal stage, and in male patients. Daily insulin dose and basal insulin requirement of those who went into remission was found to be significantly lower than in the other patients at discharge. CONCLUSIONS Decreased daily total and basal insulin requirement at discharge are valuable in predicting remission. The remission process in type 1 diabetes still has many characteristics that need to be clarified. Therefore, more extensive studies are needed.

Prevalence of idiopathic intracranial hypertension and associated factors in obese children and adolescents.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is one of the most important and rare complications of obesity. Prevalence of IIH in childhood obesity is not known. The purpose of this study was to determine the prevalence of IIH in obese children and adolescents and to investigate the relevant factors. METHODS: In this study, 1058 obese children and adolescents between 2 and 18 years of age were included. Funduscopic examination was conducted for all subjects. In cases with papilledema, increase in intracranial pressure was clarified by measuring CSF pressure with a lumbar puncture. Other causes of IIH were ruled out with clinical, laboratory tests and imaging techniques. RESULTS: Idiopathic intracranial hypertension was diagnosed in 14 subjects (1.32%). Rates of headache and systemic hypertension in subjects with IIH was determined to be 78.6% and 28.6%, respectively. Morning cortisol, fasting insulin and HOMA-IR values were found to be significantly higher in this cases (p<0.05). CONCLUSIONS: In childhood obesity, IIH should be kept in mind as a serious complication. Funduscopic examination is an easy method that suggests IIH. In particular, obese children with systemic hypertension and refractory headache should be considered for IIH.

Anthropometric findings from birth to adulthood and their relation with karyotpye distribution in Turkish girls with Turner syndrome.

To evaluate the anthropometric features of girls with Turner syndrome (TS) at birth and presentation and the effect of karyotype on these parameters. Data were collected from 842 patients with TS from 35 different centers, who were followed-up between 1984 and 2014 and whose diagnosis age ranged from birth to 18 years. Of the 842 patients, 122 girls who received growth hormone, estrogen or oxandrolone were excluded, and 720 girls were included in the study. In this cohort, the frequency of small for gestational age (SGA) birth was 33%. The frequency of SGA birth was 4.2% (2/48) in preterm and 36% (174/483) in term neonates (P < 0.001). The mean birth length was 1.3 cm shorter and mean birth weight was 0.36 kg lower than that of the normal population. The mean age at diagnosis was 10.1 ± 4.4 years. Mean height, weight and body mass index standard deviation scores at presentation were -3.1 ± 1.7, -1.4 ± 1.5, and 0.4 ± 1.7, respectively. Patients with isochromosome Xq were significantly heavier than those with other karyotype groups (P = 0.007). Age at presentation was negatively correlated and mid-parental height was positively correlated with height at presentation. Mid-parental height and age at presentation were the only parameters that were associated with height of children with TS. The frequency of SGA birth was found higher in preterm than term neonates but the mechanism could not be clarified. We found no effect of karyotype on height of girls with TS, whereas weight was greater in 46,X,i(Xq) and 45,X/46,X,i(Xq) karyotype groups.

Turner syndrome and associated problems in Turkish children: a multicenter study.

OBJECTIVE: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population. METHODS: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014. RESULTS: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosis) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto's thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%. CONCLUSION: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespan.

Growth curves for Turkish Girls with Turner Syndrome: Results of the Turkish Turner Syndrome Study Group.

OBJECTIVE: Children with Turner syndrome (TS) have a specific growth pattern that is quite different from that of healthy children. Many countries have population-specific growth charts for TS. Considering national and ethnic differences, we undertook this multicenter collaborative study to construct growth charts and reference values for height, weight and body mass index (BMI) from 3 years of age to adulthood for spontaneous growth of Turkish girls with TS. METHODS: Cross-sectional height and weight data of 842 patients with TS, younger than 18 years of age and before starting any therapy, were evaluated. RESULTS: The data were processed to calculate the 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentile values for defined ages and to construct growth curves for height-for-age, weight-for-age and BMI-for-age of girls with TS. The growth pattern of TS girls in this series resembled the growth pattern of TS girls in other reports, but there were differences in height between our series and the others. CONCLUSION: This study provides disease-specific growth charts for Turkish girls with TS. These disease-specific national growth charts will serve to improve the evaluation of growth and its management with growth-promoting therapeutic agents in TS patients.

Prevalence of Dyslipidemia and Associated Factors in Obese Children and Adolescents.

OBJECTIVE: Childhood-onset obesity is associated with increased mortality and morbidity related to cardiovascular diseases (CVD) during adulthood. Dyslipidemia has a fundamental role in the pathogenesis of CVD. This study aimed to evaluate the prevalence of dyslipidemia and related factors among obese children and adolescents. METHODS: Obese patients aged between 2 and 18 years were included in the study. Serum concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), fasting glucose levels, insulin, thyroid-stimulating hormone (TSH), free thyroxine (fT4), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver ultrasound findings were evaluated retrospectively. RESULTS: Among 823 obese patients, 353 (42.9%) met the dyslipidemia criteria: 21.7% had hypertriglyceridemia, 19.7% had low levels of HDL-C, 18.6% had hypercholesterolemia, and 13.7% had high levels of LDL-C. Older age and/or high body mass index (BMI) were related to increased prevalence of dyslipidemia. Hepatosteatosis was more common among dyslipidemic patients. The frequency of insulin resistance (IR) and of higher levels of ALT and TSH were also detected in dyslipidemic patients. Patients with both dyslipidemia and grade 2-3 hepatosteatosis had higher levels of ALT, AST and TSH and lower levels of fT4. CONCLUSION: Prevalence of dyslipidemia is high in obese children, and hypertriglyceridemia is in the foreground. Higher levels of IR and more apparent abnormal liver function test results are observed in the context of dyslipidemia and hepatosteatosis coexistence. Metabolic and hormonal alterations related with thyroid functions may also be associated with dyslipidemia and hepatosteatosis in obese patients.

Bone mineral density and vitamin D status in children and adolescents with congenital adrenal hyperplasia.

AIM: To determine the prevalence of and risk factors for decreased bone mineral density (BMD) and vitamin D deficiency in children and adolescents with congenital adrenal hyperplasia (CAH). MATERIALS AND METHODS: This study was conducted on 30 girls and 22 boys with CAH (age range = 5-20 years) with median age of 12.0 years. BMD values of lumbar vertebras (L1-L4), which were determined by dual-energy X-ray absorptiometry, were used to calculate z-scores according to chronological age. A serum 25-hydroxyvitamin D level of <15 ng/mL was considered as indicative of vitamin D deficiency. RESULTS: Mean vitamin D level was 14.8 ng/mL in the whole group. Twenty-seven (51.9%) children had vitamin D deficiency and it was more prevalent during pubertal ages. Vitamin D levels were found to be significantly lower in pubertal females. BMD z-score was below -1 standard deviation in 40.1% of cases with significantly higher mean age and lower vitamin D levels. CONCLUSION: Decreased BMD z-score and vitamin D deficiency were common in these children with CAH. Vitamin D levels were significantly lower in girls and pubertal children. Decreased BMD z-score was related to older age and lower levels of vitamin D. Periodical controls of vitamin D status and vitamin D supplementation were recommended in these cases, whenever required.

Microvascular complications in adolescents with type 1 diabetes mellitus.

OBJECTIVE: Screening of complications is an important part of diabetes care. The aim of this study was to investigate diabetic complications and related risk factors in adolescents with type 1 diabetes mellitus (T1DM). METHODS: This cross-sectional study was conducted on type 1 diabetics who were over 11 years of age or had a diabetes duration of 2 years and included 155 adolescents with T1DM (67 male, 88 female). The mean age of the patients was 14.4±2.1 years. Mean diabetes duration was 6.3±2.9 years. The patients were screened for diabetic nephropathy, retinopathy and peripheral neuropathy. RESULTS: Mean glycosylated hemoglobin (HbA1c) level of the study group was 8.4%. The frequency of microalbuminuria and peripheral neuropathy were 16.1% and 0.6%, respectively. None of the patients had diabetic retinopathy. Dyslipidemia and hypertension rates were 30.3% and 12.3%, respectively. Risk factors associated with microalbuminuria were hypertension, higher HbA1c levels, longer diabetes duration and dyslipidemia. CONCLUSION: Early diagnosis and treatment of hypertension and dyslipidemia as well as achieving a better metabolic control are important in prevention or postponement of complications in patients with T1DM. Yearly screening for diabetic nephropathy should be started 2 years after the onset of the diabetes.

Individual and familial factors associated with metabolic control in children with type 1 diabetes.

BACKGROUND: The aim of this study was to determine the individual and familial factors associated with metabolic control in children with type 1 diabetes (T1DM). METHODS: The study was performed in 93 children with T1DM between the ages of 3 and 19 years. Children and their families completed questionnaires on sociodemographics and data associated with diabetes. Medical information from the charts was also recorded. RESULTS: Older age, longer diabetes duration and higher hospitalization rate for acute complications were positively associated with poor metabolic control. Good school performance, regular hospital visits, young maternal age, high paternal education level and fewer numbers of siblings were found to be negatively associated with poor metabolic control. CONCLUSIONS: Multiple individual and family-level factors are associated with metabolic control. These data may aid in identification of diabetic children and adolescents who have a higher risk of poor metabolic control.

The association between growth response to growth hormone and baseline body composition of children with growth hormone deficiency.

OBJECTIVE: We wanted to examine the relationship between initial growth response to recombinant human Growth Hormone (rhGH) treatment and body composition in children with growth hormone deficiency (GHD). DESIGN AND METHODS: Forty-two patients (21 boys and 21 girls) aged between 5.7-15.5 years (mean age: 10.8 ± 2.6 years) with isolated GHD. The auxological and laboratory data (GH and IGF-I levels) and results of bioelectrical impedance analyses were evaluated. Children with GHD were followed up for 12 months and categorized according to growth response to rhGH into good and poor responders (change in height of > 0.7 SDS or < 0.7 SDS over one year respectively). Mean doses of rhGH per kg of fat free mass (FFM) were calculated. RESULTS: Forty-eight percent of patients showed a good growth response to rhGH therapy. At study entry, mean age, height SDS, weight SDS, serum IGF-1 SDS, IGFBP-3 SDS, growth velocity prior to rhGH therapy, GH after clonidine and l-dopa were similar in the two groups. At baseline, BMI SDS and waist-hip ratio were significantly higher in good responders (p = 0.02 and p = 0.006, respectively). Good responders had lower percentages of FFM (73.4 ± 8.9 vs. 83.1 ± 5.9) and total body water (TBW) (56.5 ± 5.3 vs. 63.1 ± 4.4), compared to poor responders (p < 0.05). There were significant correlations between changes in height SDS over one year and baseline body composition in children with GHD on rhGH treatment (r = -0.617 for percentage of FFM, r = -0.629 for percentage of TBW, p < 0.001). A correlation between BMI SDS, waist-hip ratio, mean rhGH dose per FFM and growth response was observed only in prepubertal subjects. CONCLUSION: Baseline body composition data in children with GHD can be used to predict the growth response to rhGH treatment. A management strategy that involves titrating rhGH dose according to FFM as a means of optimizing the growth response to intervention requires further study.