Standardization of Weightage Assigned to Different Segments of the Hand X-ray for Assessment of Bone Age by the Greulich-Pyle Method.

Introduction: Bone age (BA) assessment is important in evaluating disorders of growth and puberty; the Greulich and Pyle atlas method (GP) is most used. We aimed to determine the weightage to be attributed by raters to various segments of the hand x-ray, namely, distal end of radius-ulna (RU), carpals, and short bones for rating bone age using the GP atlas method. Methods: 692 deidentified x-rays from a previous study (PUNE-dataset) and 400 from the Radiological Society of North America (RSNA-dataset) were included in the study. Mean of BA assessed by experienced raters was termed reference rating. Linear regression was used to model reference age as function of age ratings of the three segments. The root-mean-square-error (RMSE) of segmental arithmetic mean and weighted mean with respect to reference rating were computed for both datasets. Results: Short bones were assigned the highest weightage. Carpals were assigned higher weightage in pre-pubertal PUNE participants as compared to RSNA, vice-versa in RU segment of post-pubertal participants. The RMSE of weighted mean ratings was significantly lower than for the arithmetic mean in the PUNE dataset. Conclusion: We thus determined weightage to be attributed by raters to segments of the hand x-ray for assessment of bone age by the GP method.

Effect of Calcium and Vitamin D Supplementation (Dairy vs. Pharmacological) on Bone Health of Underprivileged Indian Children and Youth with Type-1 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Bone health is affected by chronic childhood disorders including type-1 diabetes mellitus (T1DM). We conducted this randomized controlled trial with the objective of investigating the effect of 1-year supplementation of vitamin-D with milk or with pharmacological calcium on bone mass accrual in underprivileged Indian children and youth with T1DM. METHODS: 5 to 23year old (n = 203) underprivileged children and youth with T1DM were allocated to one of three groups: Milk (group A-received 200 ml milk + 1000 international unit (IU) vitamin-D3/day), Calcium supplement (group B-received 500 mg of calcium carbonate + 1000 IU of vitamin-D3/day) or standard of care/control (group C). Anthropometry, clinical details, biochemistry, diet (3-day 24-h recall), physical activity (questionnaires adapted for Indian children) and bone health parameters (using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography- DXA and pQCT respectively) were evaluated at enrolment and end of 12 month intervention. RESULTS: Total body less head(TBLH) bone mineral content (BMC(g)) and bone mineral density (BMD(gm/cm2)) were significantly higher at end of study in girls in both supplemented groups (TBLHBMC-A-1011.8 ±â€¯307.8, B-983.2 ±â€¯352.9, C-792.8 ±â€¯346.8. TBLHBMD-A-± 0.2, B-0.8 ±â€¯0.2, C-0.6 ±â€¯0.2, p < 0.05). Z score of lumbar spine bone mineral apparent density of supplemented participants of both sexes was significantly higher than controls (Boys- A-0.7 ±â€¯1.1, B-0.6 ±â€¯1.4, C- -0.7 ±â€¯1.1; Girls- A-1.1 ±â€¯1.1, B-0.9 ±â€¯3.4, C- -1.7 ±â€¯1.3, p < 0.05). A significantly higher percentage increase was found in cortical thickness in girls in both supplemented groups (A-17.9 ±â€¯28.6, B-15.3 ±â€¯16.5, C-7.6 ±â€¯26.2); the differences remained after adjusting for confounders. CONCLUSION: Supplementation with milk or pharmacological calcium (+vitaminD3) improved bone outcomes-particularly geometry in children with T1DM with more pronounced effect in girls. Pharmacological calcium may be more cost effective in optimising bone health in T1DM in resource limited settings.

Development of a simplified new method of bone age estimation using three bones of the hand and wrist.

Though the Greulich and Pyle (GP) method is easy, inter-observer variability, differential maturation of hand bones influences ratings. The Tanner-Whitehouse (TW) method is more accurate, but cumbersome. A simpler method combining the above, such that it utilizes fewer bones without affecting accuracy, would be widely used and more applicable in clinical practice. OBJECTIVES: 1. Devising a simplified method utilizing three bones of the hand and wrist for bone age (BA) assessment. 2. Testing whether the 3 bone method gives comparable results to standard methods (GP,TW2,TW3) in Indian children. METHODS: Developmental stages and corresponding BA for radius, hamate, terminal phalanx (left middle finger) epiphyses combining stages from GP,TW3 atlases were described; BA were rated by two blinded observers. 3 bone method ratings were compared with the same dataset analyzed earlier using GP,TW2,TW3 (4 raters). RESULTS: Radiographs analysed:493 (Girls=226). Mean chronological age:9.4 ± 4.6 yrs, mean BA 3 bone:9.8 ± 4.8 yrs, GP:9.6 ± 4.8 yrs, TW3:9.3 ± 4.5 yrs, TW2:9.9 ± 5.0 yrs. The 3 bone method demonstrated no significant inter-observer variability (p = 0.3, mean difference = 0.02 ± 0.6 yrs); a strong positive correlation (p < 0.0001) with GP (r = 0.985), TW3 (r = 0.983) and TW2 (r = 0.982) was noted. Bland-Altman plots demonstrated good agreement; the root mean square errors between 3 bone and GP,TW3,TW2 ratings were 0.6,0.7,0.6 years; mean differences were 0.19,0.49,-0.14 years respectively. Greatest proportion of outliers (beyond ±1.96 SD of mean difference) was between 6 and 8 years age for difference in 3 bone and GP, and between 4-6 years for difference in 3 bone and TW3,TW2. CONCLUSION: The 3 bone method has multiple advantages; it is easier, tackles differential maturation of wrist and hand bones, has good reproducibility, without compromising on accuracy rendering it suitable for office practice.

Stress among mothers of children with Autism Spectrum Disorder in comparison to children with & without special health care needs.

PURPOSE: Parenting a child with special health care needs (SHCN) is often stressful. This study aimed to measure and compare stress among mothers of children with (a) Autism Spectrum Disorder (ASD) - ASD group, (b) Developmental delay without ASD group, (c) SHCN without developmental delay group, and (d) Typically developing group. To assess factors associated with maternal stress in children with developmental disorders. METHODS: A cross-sectional analytical study was performed with children aged 2-12 years and their mothers. The study population was classified into four groups as defined above help of detailed history, developmental & behavioral assessments, psychological assessments, and Child Special Health Care Needs Screener (CSHCN). Parental Stress Scale (PSS) Questionnaire was administered. The main outcome measurement was the PSS and various factors affecting it. RESULTS: The mothers of the ASD group reported a high stress score (50.4±11.4) compared to SHCN without developmental delay group (38.2±8.8) and the Typically developing group (22.3±3.3) (p < 0.05) and higher but not significant stress than Developmental delay without ASD group (45.3±9.6, p > 0.05). Maladaptive behavioral issues and irregular interventions were the factors contributing to higher parental stress in the ASD group (p < 0.05). A moderate positive correlation was observed in rewarding and challenging scores of PSS among mothers of the ASD group, Developmental delay without ASD group, and SHCN without developmental delay group. CONCLUSION: Mothers of the ASD group perceived higher stress as compared to SHCN without developmental delay group and Typically developing group. Evaluation of stress and stressors is crucial for holistic management of ASD.

A comparison of bone age assessments using automated and manual methods in children of Indian ethnicity.

BACKGROUND: Bone age is useful for pediatric endocrinologists in evaluating various disorders related to growth and puberty. Traditional methods of bone age assessment, namely Greulich and Pyle (GP) and Tanner-Whitehouse (TW), have intra- and interobserver variations. Use of computer-automated methods like BoneXpert might overcome these subjective variations. OBJECTIVE: The aim of our study was to assess the validity of BoneXpert in comparison to manual GP and TW methods for assessing bone age in children of Asian Indian ethnicity. MATERIALS AND METHODS: We extracted from a previous study the deidentified left hand radiographs of 920 healthy children aged 2-19 years. We compared bone age as determined by four well-trained manual raters using GP and TW methods with the BoneXpert ratings. We computed accuracy using root mean square error (RMSE) to assess how close the bone age estimated by BoneXpert was to the reference rating. RESULTS: The standard deviations (SDs) of rating among the four manual raters were 0.52 years, 0.52 years and 0.47 years for GP, TW2 and TW3 methods, respectively. The RMSEs between the automated bone age estimates and the true ratings were 0.39 years, 0.41 years and 0.36 years, respectively, for the same methods. The RMSE values were significantly lower in girls than in boys (0.53, 0.5 and 0.47 vs. 0.39, 0.47 and 0.4) by all the methods; however, no such difference was noted in classification by body mass index. The best agreement between BoneXpert and manual rating was obtained by using 50% weight on carpals (GP50). The carpal bone age was retarded in Indian children, more so in boys. CONCLUSION: BoneXpert was accurate and performed well in estimating bone age by both GP and TW methods in healthy Asian Indian children; the error was larger in boys. The GP50 establishes "backward compatibility" with manual rating.

Neurocognitive, behavioral and socio-adaptive functioning assessment in a case of Coffin-Siris syndrome: A holistic approach/perspective beyond the identification of the disorder.

PURPOSE: Coffin-Siris syndrome (CSS) is a rare genetic disorder characterized by the presence of particular facies, congenital malformations, intellectual developmental disorder, behavioral issues, and speech and language impairment. Thorough neuropsychological assessments in the case of CSS have been reported infrequently, and its subdomains are poorly defined. A detailed description of the clinical, neurocognitive, behavioral, socio-adaptive sequelae of the patient with CSS is provided. RESULTS: The clinical diagnosis in the patient was confirmed by genetic analysis, which identified the presence of mutation of ARID1B gene; the parents' Sanger sequencing reported normal. The neuropsychological assessments revealed borderline intellectual functioning (IQ-75, verbal > performance) with a mild socio-adaptive deficit score of 64 as suggested by the adaptive scale. The behavioral profile reported that the child had significant difficulties in the attention subdomain with concern in social and thought subdomains. The child met the profile for mild severity of Autism Spectrum Disorder and did not meet the criteria for Attention Deficit Hyperactivity Disorder. In addition, the child had scholastic difficulties in reading and mathematical skills. CONCLUSION: Neurocognitive, behavioral, socio-adaptive functioning and comorbidity assessment in order to provide holistic management of such children after thorough evaluation is essential for their overall functioning.

Comparison of Bone Age Assessments by Gruelich-Pyle, Gilsanz-Ratib, and Tanner Whitehouse Methods in Healthy Indian Children.

BACKGROUND: There are several methods of bone age (BA) assessment, which include Gruelich-Pyle (GP), Gilsanz-Ratib (GR), and Tanner Whitehouse-3 (TW-3) methods. Although GP atlas is the most widely used, there are concerns about its accuracy in children of different ethnicities, making the use of the TW-3 method an attractive option in Indian children. OBJECTIVES: 1) To assess the relationship of BA with chronological age (CA) as assessed by different methods (GP, GR, and TW-3) in healthy Indian children 2) To assess which of the three methods of BA assessment is more suitable in Indian children. METHODOLOGY: X-rays of 851 children (438 boys and 413 girls, aged 2-16.5 years) were analyzed by four independent observers using three different methods of BA estimation (GP, GR, and TW-3). Mean BAs were converted to Z-scores. For purpose of deciding which method of BA was most suitable in our cohort, a test of proportions and root mean square (RMS) deviations were computed. RESULTS: Using the test of proportions, the TW-3 method was most suitable overall (P < 0.05). TW-3 method was again most applicable in prepubertal boys (P < 0.05), in prepubertal girls (although not significant, P > 0.1), and pubertal girls (P < 0.05). However, in pubertal boys, the GR atlas method was most suitable (P < 0.05). The same results were obtained when root mean square (RMS) deviations were computed. Interestingly, BA was underestimated in Indian boys irrespective of the method used. In Indian girls, however, the BA was underestimated till the pubertal growth spurt, after which there was rapid advancement of BA. CONCLUSIONS: Among the three methods (GP, GR, and TW-3), the BAs estimated by the TW-3 method were closest to CAs. Hence, it seems reasonable to recommend the use of the TW-3 method for BA estimation in the Indian population till an Indian standard bone age atlas is developed.

Clinical, Etiological and Laboratory Profile of Children with Disorders of Sexual Development (DSD)-Experience from a Tertiary Pediatric Endocrine Unit in Western India.

OBJECTIVES: To present the clinical profile, diagnostic work-up, and management of children with Disorders of Sexual Development (DSD). MATERIALS AND METHODS: A retrospective study from a tertiary pediatric endocrine unit of western India. We included 39 patients who presented over a period of 9 years from June 2009 to June 2018. RESULTS: Nineteen patients (48.7%) were diagnosed with 46 XY DSD, 16 (41%) with 46 XX DSD, and 4 (10.3%) with sex chromosomal DSD. Out of 46 XY DSD, androgen insensitivity was observed in 8 (42.1%) patients, 5 alpha-reductase deficiency in 5 (26.3%), gonadal dysgenesis in 3 (15.8%), ovotesticular DSD in 2 (10.5%) and 17 beta-hydroxylase (17γ-HSD3) deficiency in 1 (5.3%). Congenital adrenal hyperplasia was the most common cause in 46 XX DSD observed in 11 (68.75%) out of 16 patients, ovotesticular DSD was seen in 4 (25%) patients and testicular DSD in 1 (6.25%) patient. In sex chromosomal DSD 3 (75%) patients had mixed gonadal dysgenesis and 1 (25%) had ovotesticular DSD out of a total of 4 patients. At presentation gender of rearing was assigned as male in 16 (41%) patients, female in 20 (51.3%) patients, and no gender was assigned in 3 (7.7%). The gender of rearing was changed after diagnosis in 6 (16.7%) children. CONCLUSION: CAH was the most common etiology of 46 XX DSD whereas androgen insensitivity among 46 XY DSD. Assigning the sex of rearing should not be hurried and should be done only after diagnosis and parental counseling. A multidisciplinary and systematic approach is required for children with DSD.

Appropriateness of Lower Waist Circumference Cutoffs for Predicting Derangement in Metabolic Parameters Among Asian Children and Adolescents: A Pilot Study.

Waist circumference (WC) >90th percentile cut-off effectively screens children for metabolic syndrome, as some specific metabolic derangements (high fasting serum levels of insulin and triglycerides) may be better associated with lower (70th percentile) waist circumference cut off. We evaluated a subset of children and adolescents found obese or overweight following the anthropometric screening in a school-based survey. Metabolic parameters (fasting insulin levels, fasting blood sugar and fasting lipid profile and blood pressure) were compared among 3 groups of obese or overweight children divided on the basis of WC percentiles (>90th, 70th-90th and <70th). 78 children (aged 11-18 years, 45 boys) were evaluated. The proportion of participants with high triglycerides and fasting insulin among those with WC<70th (28.6%, 19%) was significantly lower than that in the group with WC >90th (76.9%, 53.8%) as well as in group with WC 70th-90th percentile (38.7%, 41.9%).

Sexual maturity assessment in Indian children-a study from western India.

OBJECTIVES: Pubertal assessment is crucial as puberty is the transition from childhood to adulthood. Pubertal assessment, growth, and secular trend in puberty need to be explored further in India. The objectives were to assess Sexual Maturity Rating (SMR) among children and establish normative data of puberty from western India. We also compared age of attainment of various stages of puberty with BMI and secular trend in menarche. METHODS: A cross-sectional observational study was undertaken at a tertiary care pediatric center. The study population were healthy girls and boys between 6 and 18 years. Demographic data was noted. Anthropometry and SMR assessment (Tanner staging) were performed. The age of menarche was noted among the girls and their mothers. Data were analyzed using SPSS 21. RESULTS: In girls, median age of thelarche, pubarche, and menarche was 9.37 (8.5-10.2), 10.18 (9.87-10.49), and 12.55 years (12.41-12.75) respectively. There was an early appearance of thelarche but menarche was delayed in overweight-obese girls (statistically not significant). Age of menarche showed a shift to left in girls as compared to their mothers (p=0.036). In boys, median age of testicular stage 2 and pubarche was 10.7 (9.9-11.8) and 11.6 years (11.1-12.1) respectively. In overweight-obese boys the pubertal milestones were achieved earlier (statistically not significant). CONCLUSIONS: Normative data on pubertal assessment from western India is presented. Age of menarche shows a shift to left in girls as compared to their mothers. Pubertal milestones were observed at a younger age in overweight obese children which was not significant.

Extended growth charts for Indian children.

OBJECTIVES: While growth charts depicting 7 percentile lines for height and weight are useful for healthcare workers and pediatricians, endocrinologists need indication-specific z score cutoffs to plan investigations and treatment. The current Indian charts do not offer lower percentile/z scores (-2.25, -2.5, and -3 z score) lines. Also, increasing prevalence of childhood overweight and obesity necessitates a quick screening of nutritional status without calculations while using the same growth chart. Our objectives were to produce extended and user-friendly growth charts for 0-18-year-old Indian children that depict -2.25, -2.5, and -3 z score height lines in addition to the standard 7 lines and to add a quick BMI assessment tool as an inset. METHODS: LMS values from IAP 2015 growth charts (5-18 years) and WHO 2006 MGRS charts (<5 years) were used to generate -2.25, -2.5, and -3 z score height lines (1.2, 0.6, and 0.1 percentiles, respectively) from 0-18 year for boys and girls. These newly generated lines were added to standard 7 (3, 10, 25, 50, 75, 90, 97) percentile lines for height charts. In addition, modified BMI quick screening tool was incorporated as an inset. RESULTS: The extended height charts (with 10 lines), standard (7 lines) weight charts, and quick BMI assessment tool are presented in a single unified chart for use by endocrinologists. CONCLUSIONS: These charts will help in defining specific height z score cutoffs as well as screen for overweight and obesity without any calculations in Asian Indian children.

Test Anxiety among School-Going Children and Adolescents, Factors Affecting and Impact on Quality of Life: A Multicenter Study.

OBJECTIVE: To assess test anxiety (TA) and factors affecting TA in school-going children. To observe the impact of TA on quality of life (QOL). METHOD: A multi-centric cross-sectional observational study was conducted in Indian schools from 6 different states in both rural and urban settings. Indian school children 9 to 18-y-old were the subjects. Demographic data, including age, gender, and socioeconomic status, were obtained. Children were administered Test Anxiety Inventory (TAI) and PedsQL (Pediatric Quality of Life). TAI score (and factors affecting it in both rural and urban children) and QOL scores were assessed. RESULTS: Data on 2158 children were analyzed (1162 boys). The mean age was 13.8 ± 1.8 y, and the mean TAI score was 48.3 ± 10.2. TAI score was significantly higher in girls and rural children (p < 0.05 for both). Based on the TAI score, high, medium, and low-anxiety clusters were generated. Proportion of children with high, medium and low-anxiety scores were 18%, 48%, and 34%, respectively. Children with low anxiety had better QOL in all subdomains (p < 0.05). Regression analysis indicated increasing age, low QOL, urban living, and lower maternal education as significant predictors of high anxiety (p < 0.05). CONCLUSION: Girls and rural children had higher TA. Two-thirds of children studied had moderate to high TA. Increasing age, urban living, QOL, and maternal education had an impact on TA. Evaluating TA and developing appropriate strategies for stress-reduction in school children is necessary.

Factors influencing growth in children with growth hormone deficiency - a case-control study.

INTRODUCTION: To assess the response of South Indian children with growth hormone deficiency (GHD) to growth hormone therapy, optimal duration of therapy for good catch up, and factors determining the response of our children to growth hormone therapy. MATERIAL AND METHODS: We conducted a case control study at a paediatric endocrine unit of a tertiary paediatric hospital. Children diagnosed with growth hormone deficiency were initiated on GH (cases) or followed up without GH therapy (controls). Detailed clinical, biochemical, radiological, and treatment parameters were recorded at baseline and follow-up. Data were analysed using IBM SPSS version 21. RESULTS: We enrolled 23 subjects in group I (cases who received GH) and group II (controls with untreated children), and both the groups were comparable at baseline. Group I (-4.12 ±1.7 to -2.81 ±1.52) had significant height increase on follow-up after GH therapy compared to group II (-3.55 ±1.7 to -3.51 ±1.52) (p > 0.05). Growth velocity in group I (13.25 ±5.6 cm/year, SD score 4.55 ±5.42) was significantly higher compared to group II (3.4 ±1.8 cm/year, SD score -1.62 ±2.38). Duration of growth hormone therapy, presence of ectopic posterior pituitary, and BA: CA ratio independently impacted the growth velocity SD scores. Kaplan Meier analysis curve showed 15 months of GH therapy was needed to attain a height within ±2 SD of the target height. CONCLUSIONS: Early diagnosis, pre-pubertal status, delayed bone age, and presence of ectopic posterior pituitary on MRI are determinants of a better response. Growth hormone must be administered for at least 15 months for catch up height SDs within target height SD range.

Clinical application of a novel next generation sequencing assay for CYP21A2 gene in 310 cases of 21- hydroxylase congenital adrenal hyperplasia from India.

PURPOSE: Accurate diagnosis is required for management of Congenital adrenal hyperplasia (CAH). The conventional method for detection of mutations in the CYP21A2 gene is targeted capillary sequencing which is labor intensive and has limited multiplexing capability. Next generation sequencing (NGS) provides data with high sequence coverage and depth. Our objective was to develop an accurate NGS-based assay to characterize the mutation spectrum in CYP21A2 gene in Indian patients suspected to have 21-OH CAH. METHODS: Cases with 21-OH CAH from 12 endocrine units across India were studied. DNA was extracted from proband's and parent's(subset) blood. Locus-specific long-range PCR and gel electrophoresis of amplicons was followed by NGS where no visible 30 kb homozygous/whole gene deletion was observed. Orthogonal confirmation was performed by capillary sequencing (ABI 3500) and Multiplex Ligation-dependent Probe Amplification (MLPA, MRC-Holland). PCR products were purified and individual libraries were pooled and sequenced (Illumina). RESULTS: Of the 310 CAH cases, biallelic mutations (pathogenic/ likely pathogenic variants involving both CYP21A2 gene copies) were detected in 256 (82.6%), heterozygous mutations in 13 (4.2 %), and none in 41 (13.2%). Most common mutation was c.293-13A/C>G (29.03%), followed by 30 kb deletion (18.24%). Thirty samples tested orthogonally (by capillary sequencing or MLPA) showed 100% concordance with NGS assay. Nine novel variants were identified. CONCLUSIONS: We have developed and validated a comprehensive NGS-based assay for detection of variants in CYP21A2 gene in patients with 21-OH CAH. We describe CYP21A2 mutation spectrum and novel variants in a large cohort of Indian patients with CAH.

Diabetes distress in Indian children with type 1 diabetes mellitus and their mothers.

BACKGROUND: Children and their mothers, who are usually the primary caregivers, are likely to be distressed due to type 1 diabetes (T1DM). OBJECTIVES: (1) To assess diabetes-specific distress (DD) perceived by children and adolescents with T1DM and their mothers and association of distress between children and mothers. (2) To study the association of diabetes distress with glycemic control and disease duration. SUBJECTS: Children and adolescents with T1DM over eight years and their mothers. METHODS: Clinical data were recorded. DD was assessed by Problem Associated in Diabetes-Pediatric (PAID-Peds) (range 0-80) and Problem Associated in Diabetes-Parents Revised (PAID-PR) (range 0-72) questionnaires (higher scores indicate higher distress); administered to children and mothers, respectively. Sub-dimensions in questionnaires included diabetes-related emotional problems, and treatment-, food-, and social support-related problems. Correlation analysis (Spearman's) was performed, and a paired t-test was used to compare PAID-Peds and PAID-PR (SPSS 25). RESULTS: Mean PAID-Peds and PAID-PR scores in 67 children and mothers were 24.4 ± 18.1 and 31.9 ± 21.5, respectively (p=0.009), and a significant correlation was noted between their scores (R=0.45, p=0.001). PAID-Peds score was positively associated with HbA1c (R=0.25, p=0.04). Diabetes-related emotional problems of mothers and children (R=0.38, p=0.003), treatment problems (R=0.5, p=0.001), and food problems (R=0.24, p=0.05) correlated positively. Subdimension scores were significantly different in children and mothers except in the social support domain. CONCLUSION: DD was higher in mothers than children; higher distress in children was associated with poor metabolic control. Evaluation of DD needs to be performed in children with T1DM.

Body Mass Index Quick Screening Tool for Indian Academy of Pediatrics 2015 Growth Charts.

OBJECTIVE: To develop gender-specific graphic tool in which BMI cut offs can be read from height and weight, without need for calculating BMI and to validate the tool against Indian Academy of Pediatrics (IAP) 2015 BMI charts. METHODS: Validation of tool was performed using de-identified data on children from school health surveys. RESULTS: For detection of overweight and obesity, the BMI tool had sensitivity of 95.7% and specificity of 85.7% for boys, and 95.7% and 89.7% for girls, respectively. For underweight, sensitivity of 100% for boys and girls, and specificity of 88.9% for boys and 82.4% for girls was observed. CONCLUSION: We present a graphic BMI tool for screening for underweight, overweight and obesity, which complements the existing IAP charts.

A Targeted Next Generation Sequencing Panel for Non-syndromic Early Onset Severe Obesity and Identification of Novel Likely -Pathogenic Variants in the MC4R and LEP Genes.

OBJECTIVES: To screen for variants in the MC4R and LEP genes in 46 patients with clinical suspicion of non-syndromic early onset severe obesity (NEOSO). METHODS: Children with early onset obesity satisfying WHO criteria of obesity were studied. The MC4R and LEP genes were sequenced using a PCR amplicon based NGS on Illumina MiSeq next generation sequencer using an in-house developed protocol. RESULTS: Of the 46 children tested, four were found to have novel pathogenic/likely-pathogenic variants (one in the MC4R gene and three in the LEP gene). In three out of the 4 families, the presence of the variants was confirmed using standard bidirectional capillary sequencing in the probands. CONCLUSIONS: Four children with novel likely pathogenic variants in the MC4R and LEP genes are reported. Genetic analysis is crucial in children with early onset obesity and should be considered.