Normal Height Research Articles

THU143 A Novel Maternally Inherited GNAS Variant In A Family With Hyperphagia And Obesity

Abstract Disclosure: P. Purushothaman: None. A. Ramakrishnan: None. E.F. Gevers: None. Introduction: Heterozygous inactivating mutations in the maternal allele of the GNAS gene typically result in pseudohypoparathyroidism (PHP) characterized by developmental delay, short stature, obesity, hormone resistance and bone abnormalities. Recently, GNAS variants were also described in 1% of patients in the UK Genetics of Obesity cohort, resulting in reduced MC4R signalling. Here, we report another novel GNAS variant in family with hyperphagia and obesity and only mild features of PHP. Case: The proband presented at 6 years with hyperphagia and obesity from age 3 years. BMI was 30.4 (4.1 SDS) with height +1.9 SDS, and head circumference (HC) + 3.0 SDS. She had subtle brachydactyly, short toes and a café au lait patch. Developmental milestones and cognitive achievements were mildly delayed. Her 12-year-old brother [ height +2.1 SDS, weight +3.1 SDS, BMI 29.55 (2.9 SDS), HC +3.6 SDS] had been followed in an obesity clinic for a few years with hyperphagia, obesity, delayed developmental milestones and a recent diagnosis of autism. He also had subtle brachydactyly, as did the mother who was also obese (BMI 38.9) with a normal height but had normal cognition. Results: In the proband, initial investigations did not suggest hormone resistance. However, at 8.7 years, PTH was high [9.5 pmol/L (0.7-5.6)] with normal calcium and Vitamin D; TSH 6.6 mU/L (<6), FT4 11.8 pmol/L (10.8 - 19.0). She had hyperlipidaemia and fatty liver. X-ray hand showed generalised mild brachydactyly with a short right fifth metacarpal. In the brother, PTH tested for the first time at 12.9 years was 18.4 pmol/L (1.6-6.9), calcium and vitamin D were normal; TSH 4.04 mU/L (<4.2) and FT4 13.4 pmol/L. Next Generation Sequencing using the Cambridge Obesity gene panel detected a novel heterozygous (c.791A>C, p.(Asn264Thr) variant in exon 10 of GNAS in the proband and subsequently in the mother and brother confirming maternal inheritance. This variant has not been reported in control databases (1000 Genomes, ESP, ExAC and gnomAD, Human Gene Mutation Database and ClinVar). The variant is in a highly conserved region susceptible to missense mutations and has been classified as pathogenic using ACMG and ACGS guidelines. Discussion: In conclusion, we describe a novel heterozygous inactivating GNAS variant c.791A>C, p.Asn264Thr resulting in hyperphagia, obesity, developmental delay, macrocephaly, mild brachydactyly, tall stature and variable biochemical mild hormone resistance in 2 siblings and resulting in obesity, mild brachydactyly without cognitive impairment in the mother. These cases demonstrate the clinical heterogeneity of the monogenic disease. Clinical and biochemical screening for PHP and genetic screening for GNAS variants should be performed in patients presenting with obesity, even in the absence of classical signs of PHP, to reduce diagnostic delay. Presentation: Thursday, June 15, 2023

THU243 Fitting Together The Pieces Of The Puzzle Between Isolated ACTH Deficiency And Immunodeficiency: DAVID Syndrome

Abstract Disclosure: K.V. Buchanan: None. A.C. Hurst: None. A.P. Ashraf: None. Objectives: DAVID syndrome is a rare genetic disorder with common variable immunodeficiency (CVID) and anterior pituitary hormonal deficiencies due to a pathogenic variant in NFKB2. We aim to describe asymptomatic ACTH deficiency identified after the diagnosis of CVID in a patient with DAVID syndrome. Methods: A retrospective chart review of a patient with DAVID syndrome was performed. Results: The patient is a 15 year and 9-month-old female with weight in the 71st percentile and height in the 64th percentile, who was diagnosed with DAVID syndrome at 10 years through a Primary Immunodeficiency panel which identified a pathogenic variant in NFKB2 c.2557C>T,p.Arg853* and a variant of unknown significance in STAT2 c.1301C>T (p.Thr434Met). The panel was performed due to the patient’s history of recurrent sinus infections, hypogammaglobulinemia, and alopecia totalis. The patient did not have symptoms of ACTH deficiency including hypoglycemia and hypotension. After the genetic diagnosis was made, an anterior pituitary hormone evaluation was performed which showed an ACTH <5 pg/ml, AM cortisol <0.2 mcg/dL, TSH 3.48 uIU/ml, FT4 0.82 ng/dL, thyroid peroxidase antibody 29 IU/mL (normal <9), somatomedin-c 44 ng/mL (reference range 152-593), LH 5.36 mIU/mL, and FSH 14.25 mIU/mL. Adrenal insufficiency was diagnosed since the patient did not show incremental cortisol response (serum cortisol <0.2 mcg/dL at 30 and 60 minutes) post Cosyntropin stimulation test. The patient had normal electrolytes. Hydrocortisone replacement therapy was initiated. A growth hormone stimulation test was not performed since the patient had normal height and interval height velocity. The thyroid function remained stable, and the patient attained menarche at age 14. Conclusions: This patient is unique in having asymptomatic, acquired, isolated ACTH deficiency diagnosed in later childhood, despite having frequent sinopulmonary infections since infancy as part of DAVID syndrome. Further research needs to be done to elucidate how NFKB2 variants contribute to acquired, isolated, central ACTH deficiency or autoimmune pituitary disease. Presentation: Thursday, June 15, 2023

THU168 PRMT7 Gene Mutation—A Rare Genetic Syndrome With Novel Endocrine Associations

Abstract Disclosure: K. Nutakki: None. S. Nalla: None. P. Deb: None. A. Vulpala: None. Background: Causes of short stature in children include pathologic causes (genetic diseases, underlying systemic disease, or growth hormone deficiency) and non-pathological variants such as familial and constitutional short stature. Genetic causes include Turner’s syndrome, SHOX mutations, Noonan’s syndrome and Silver- Russel syndrome besides others. Homozygous/compound heterozygous mutations in Protein Arginine Methyltransferase 7 (PRMT7) can result in Short Stature, Brachydactyly, Intellectual Developmental Disability and Seizures syndrome (SBIDDS) . Here, we report a child with SBIDDS syndrome who has associated endocrine manifestations of growth hormone deficiency and primary hypothyroidism. Case report: A 9-year-old male child, twin A of dichorionic diamniotic gestation, presented to the Endocrine OPD with short stature. There was a history of developmental delay, seizure disorder and mild intellectual deficit. Excessive weight gain was observed since 4 years of age. On examination, he was short with abdominal obesity, brachydactyly, simian crease and macroglossia. Height was below 3rd centile and weight at the 97th percentile. SMR was pre-pubertal. Investigations confirmed primary hypothyroidism.GH deficiency (peak GH after clonidine stimulation was less than 4 microgram/L) and reduced IGF-I levels were also found. Twin B was noted to have a normal height percentile. In both, skeletal maturation was consistent with chronological age. Twin A was treated with rGH and levothyroxine and responded well to rGH treatment. Whole exome sequencing revealed homozygosity for PRMT7 mutation in twin A with both parents heterozygous for the same gene mutation. His twin sibling, twin B was also found to be homozygous for the mutation, but he did not display any characteristics of the syndrome. Discussion: To the best of our knowledge, this is only the second reported case of SBIDDS syndrome (PRMT7 mutation) with documented growth hormone deficiency and only case with documented primary hypothyroidism. Height gain observed over the period of rGH treatment is suggestive of a possible role of GH/IGF-I axis alterations as contributors of growth impairment in these children. PRMT7 encodes for an arginine methyltransferase, involved in several biological processes, such as DNA transcription and repairing, RNA splicing, cell differentiation. We would like to propose that children with SBIDDS syndrome may be tested for GH deficiency as part of their overall assessment. Likewise, it should be further explored if PRMT7 gene mutation testing should be recommended in a child presenting with short stature and one or more manifestations of SBIDDS syndrome. Presentation: Thursday, June 15, 2023

THU175 Incorrect Age Causing Falsely Short Stature In An Afghan Immigrant Girl

Abstract Disclosure: J. Ing: None. M. Marinkovic: None. Background: Evaluation for short stature routinely includes screening for hormone deficiencies, chromosomal abnormalities, gastroenterological diseases, and inflammatory processes. “Incorrect age” resulting in falsely short stature, is not often considered in the differential diagnosis. Clinical Case: A young girl who recently immigrated to the United States from Afghanistan was referred for endocrine evaluation for short stature. At the time of her initial visit, she was listed in the electronic medical record at 10 years and 0 months old. Her medical history was significant for bowel injuries sustained three years prior in a bombing incident that required surgery and from which she completely recovered. Available growth charts from the preceding 6 months showed height and weight consistently less than the 1st percentile for her age but normal height velocity. On the exam she was prepubertal. Her measured height was 117.8 cm (0.06th percentile, Z = -3.24) and her body mass index (BMI) was 14.7 kg/m2 (12th percentile, Z = -1.18). The patient’s calculated mid-parental height was 155.5 cm (12.5th percentile, Z = -1.15). Laboratory work-up obtained by the pediatrician showed normal IGF-1, IGFBP-3, TSH, free and total thyroxine, tissue transglutaminase IgA, sedimentation rate, urinalysis, complete blood panel, complete metabolic panel, and a normal 20 cell count karyotype (46, XX). Her bone age was 5 years and 6 months and was interpreted as markedly delayed. Upon further history gathering using a Pashto interpreter, her father revealed there was an error in the processing of her immigration documents, resulting in being listed as three years older than her actual age. When corrected to that of a 7 year and 0 month old girl, her height improved to the 23rd percentile (Z = -0.73), and her BMI to the 31st percentile (Z = -0.5). Conclusion: This case demonstrates how children, through the immigration process, may have their age incorrectly documented and thereby are at risk for unnecessary and costly medical evaluation. It is possible that language barriers play a role in such errors. Therefore, it is important to verify the patient's true age, as parents may not think to provide this information voluntarily. Presentation: Thursday, June 15, 2023

Effect of body mass index on soft tissues in adolescents with skeletal class I and normal facial height.

The evaluation of soft tissues in patients undergoing orthodontic treatment plays a critical role in diagnosis and treatment planning. This study aims to evaluate the effect of body mass index (BMI) on facial soft tissues in skeletal Class I patients with normal vertical growth. The study included 72 patients with a normal vertical growth pattern (SN-GoGn 26-38°) and skeletal Class I (ANB 2‒4°) malocclusion. According to their BMI (kg/m2) values, the patients were divided into three groups of 24 individuals each: underweight (>5th percentile) (13 females, 11 males; mean age, 11.58 ± 1.95 years), normal weight (5‒85th percentile) (12 females, 12 males; mean age, 11.54 ± 1.95 years), overweight (85‒95th percentile) (12 females, 12 males; mean age, 11.62 ± 2.01 years). Soft tissue thickness and height measurements were made on lateral cephalometric radiographs. In all soft tissue thickness measurements, except for the nasion, the overweight weight group had higher values. In comparing the underweight and normal weight groups, statistically significant differences were found in the thickness measurements at the nasion and gnathion (p < 0.05). The differences in thickness measurements at the glabella, labiale superius, stomion, labiale inferius, pogonion, gnathion, and menton are statistically significant between the underweight and overweight groups (p < 0.005). Comparing the normal and overweight groups revealed statistically significant differences the thickness measurements at the glabella, labiale superius, stomion, pogonion and menton (p < 0.05).

Multi-Institutional Phase I Feasibility Trial of Vertebral Body Sparing CSI for Pediatric Brain Tumors

Craniospinal irradiation (CSI) is an essential part of curative treatment for several pediatric brain tumors. Proton CSI allows for sparing of the organs anterior to the vertebral bodies (VBs), but this technique still includes the entire VB in the target for growing children. providing no advantage in marrow sparing or adverse effects on growth. Advances in proton therapy including Proton Beam Scanning (PBS) allow for delivery of proton CSI with substantial vertebral body sparing (VBS). We sought to determine the feasibility of VBS CSI using PBS based on the effects on tumor control and growth, and the occurrence of grade III/IV hematologic toxicity. Clinical and treatment characteristics were recorded for 20 pediatric patients with medulloblastoma (n = 14) or germ cell tumor (GCT) (n = 6) who received proton VBS CSI without concurrent chemotherapy or with concurrent single-agent vincristine in a multi-institutional clinical trial. The following standard variables were extracted for each patient: age, histology, radiation dose, chemotherapy regimen, and growth hormone replacement status. Complete blood counts (CBC) with differential and data on height/weight were recorded at baseline pre-RT, weekly during RT, and after completion of cancer treatment. Hematologic toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 (CTCAE v4). Median age of 13 male and 7 female patients receiving proton VBS CSI was 10 years (range: 5.1 - 15.1). All GCT patients (n = 6, 30%) received pre-RT chemo. Median CSI dose was 23.4 Gy (range: 21.0 - 37.8), and total dose to tumor bed was 54 Gy in 18 patients (90%) while 2 patients with pure germinoma received a total dose of 36 and 37.5 Gy, respectively. 11 patients (55%) did not receive concurrent vincristine. At a median follow up of 26.4 months (range: 12.5 - 56.3) from the start of RT, no patients relapsed. 17 patients (85%) developed grade ≥3 hematologic toxicity including grade 3 lymphopenia (n = 16), leukopenia (n = 9), neutropenia (n = 8), anemia (n = 1), and grade 4 neutropenia (n = 1). The patient who developed grade 4 neutropenia had low white blood counts prior to RT. 14 patients (70%) received post-RT chemo. No patients required platelet transfusion during RT. Those findings are similar to historical controls. 4 patients started growth hormone replacement therapy after RT. No patients developed spine deformities after the completion of treatment. Proton VBS CSI is a feasible and well tolerated treatment for children with brain tumors. Longer follow up is needed to assess for late effects on tumor control. It is too early to assess for height in this cohort but for the patients that had longer follow up, normal height was achieved.

Realizing the European Vertical Reference System using model-based hydrodynamic leveling data

All realizations of the European Vertical Reference System (EVRS) computed so far are solely based on geopotential differences obtained by spirit leveling/gravimetry. As such, there are no direct connections between height benchmarks separated by large water bodies. In this study, such connections are added by means of model-based hydrodynamic leveling resulting in a new, yet unofficial realization of the EVRS. The model-derived mean water levels used in computing the hydrodynamic leveling connections were obtained from the Nemo-Nordic (Baltic Sea) and 3D DCSM-FM (northwest European continental shelf) hydrodynamic models. The impact of model-based hydrodynamic leveling on the European Vertical Reference Frame is significant, especially for France and Great Britain. Compared to a solution which only uses spirit leveling/gravimetry, the differences in these countries reach tens to hundreds of hbox {kgal}, hbox {mm}. We also observed an improved agreement with normal heights obtained by differencing GNSS and the European gravimetric quasi-geoid 2015 (EGG2015) heights. In Great Britain, the south-north slope of 48 mm hbox {deg}^{-1} present in the solution which uses only spirit leveling/gravimetry data reduced to 2.2 mm hbox {deg}^{-1}. In France, the improvement is confined to the southwest. The choice of the period over which water levels are averaged has an impact on the results as it determines, among others, the set of tide gauges available to establish the hydrodynamic leveling connections. When using an averaging period that can be considered as the least preferred choice based on three established criteria, the positive impact for France has gone. For Great Britain, the estimated south-north slope became 12.6 mm hbox {deg}^{-1}. This is larger than the slope obtained using the most preferred averaging period but still substantially lower compared to the slope associated with a solution that uses only spirit leveling/gravimetry.

The International X-Linked Hypophosphatemia (XLH) Registry: first interim analysis of baseline demographic, genetic and clinical data

BackgroundX-linked hypophosphatemia (XLH) is a rare, hereditary, progressive, renal phosphate-wasting disorder characterized by a pathological increase in FGF23 concentration and activity. Due to its rarity, diagnosis may be delayed, which can adversely affect outcomes. As a chronic disease resulting in progressive accumulation of musculoskeletal manifestations, it is important to understand the natural history of XLH over the patient’s lifetime and the impact of drug treatments and other interventions. This multicentre, international patient registry (International XLH Registry) was established to address the paucity of these data. Here we present the findings of the first interim analysis of the registry.ResultsThe International XLH Registry was initiated in August 2017 and includes participants of all ages diagnosed with XLH, regardless of their treatment and management. At the database lock for this first interim analysis (29 March 2021), 579 participants had entered the registry before 30 November 2020 and are included in the analysis (360 children [62.2%], 217 adults [37.5%] and 2 whose ages were not recorded [0.3%]; 64.2% were female). Family history data were available for 319/345 (92.5%) children and 145/187 (77.5%) adults; 62.1% had biological parents affected by XLH. Genetic testing data were available for 341 (94.7%) children and 203 (93.5%) adults; 370/546 (67.8%) had genetic test results; 331/370 (89.5%) had a confirmed PHEX mutation. A notably longer time to diagnosis was observed in adults ≥ 50 years of age (mean [median] duration 9.4 [2.0] years) versus all adults (3.7 [0.1] years) and children (1.0 [0.2] years). Participants presented with normal weight, shorter length or height and elevated body mass index (approximately − 2 and + 2 Z-scores, respectively) versus the general population. Clinical histories were collected for 349 participants (239 children and 110 adults). General data trends for prevalence of bone, dental, renal and joint conditions in all participants were aligned with expectations for a typical population of people with XLH.ConclusionThe data collected within the International XLH Registry, the largest XLH registry to date, provide substantial information to address the paucity of natural history data, starting with demographic, family history, genetic testing, diagnosis, auxology and baseline data on clinical presentation.

Evaluation of Clinical Characteristics and Growth Hormone Response in a Rare Skeletal Dysplasia: Pycnodysostosis.

Introduction Pycnodysostosis is a rare osteosclerotic skeletal dysplasia; its clinical features include short stature, characteristic facial features, increased bone fragility, and acro-osteolysis of the distal phalanx. Lack of clear guidelines for treatment and follow-up in rare diseases such as pycnodysostosis with growth hormone (GH) deficiency poses a difficulty for the clinician. This study aims to identify clinical, radiological, and endocrine findings of patients with pycnodysostosis focusing on the first year of recombinant human growth hormone (rhGH) treatment response. The eminence of this study is that it presents clinical experience with rhGH, providing an approach for future similar cases. Methods Three girls and two boys from three different families diagnosed with pycnodysostosis via clinical, radiological, and genetic evaluation followed up in the pediatric endocrinology clinic between 2022 and 2023 were enrolled in this study. Clinical findings, anthropometric measurements (weight, height, body mass index [BMI]), and laboratory, radiological, and genetic examinations were evaluated retrospectively. Participants were evaluated for GH deficiency using L-DOPA and clonidine tests if growth rate was below -2 standard deviation score (SDS) for gender and age after one-year follow-up. Results Complaints on admission were short stature (80%) and recurrent bone fractures (20%). Characteristic facial features and brachydactyly were seen in all the patients. Median height SDS on admission was -3.0 (range: -1.9 to -3.8). Median height SDS on last clinic visit was -3.2 (range: -1.7 to -4.2) at a median age of 8 years (range: 3.5-14 years). BMI was normal in four patients, while one was overweight. Bone mineral densitometry z-score was high, and two patients had bone fractures following minor trauma, while one had recurrent fractures. Two siblings (first and second cases) and the third case were diagnosed with GH deficiency, and anterior pituitary hormones were normal otherwise. One had partial empty sella in hypophyseal magnetic resonance imaging. rhGH (33 mcg/kg/day, subcutaneously) was started. Growth rate of the first, second, and third cases increased from 3.3, 3.1, 3.9 to 5, 4.3, 7.2 cm/year, respectively. Prior to rhGH, two had adenoid hypertrophy which was stable following rhGH. Growth rate follow-up of the fourth case continues, while the fifth case, the only participant who has reached adult height, has normal height according to age and gender normative. Conclusion Although rare, pycnodysostosis should not be overlooked in a patient with characteristic facial features, disproportionate short stature, and recurrent fractures. GH deficiency should be evaluated early if growth rate is declining. rhGH may restore growth rate and the possibility of catch-up in growth in patients with pycnodysostosis and GH deficiency. Hence, after first year of rhGH, growth rate of patients with pycnodysostosis is lower when compared to other etiologies of GH deficiency.

Developmental enamel defects and dental anomalies of number and size in children with growth hormone deficiency

Growth hormone is meaningfully involved in the processes of tooth cells differentiation and tissue formation. The aim of the study was to evaluate the occurrence of dental anomalies: microdontia, macrodontia, hypodontia and developmental defects of enamel (DDE) amongst a group of isolated growth hormone deficient (GHD) patients and healthy children. This cross-sectional study was based on a group of 101 Caucasian children: 33 with GHD (mean age 10.94, SD 2.51) and 68 being healthy, normal height subjects (mean age 10.4, SD 2.38). The dental examination in primary and permanent teeth was carried out by one trained and calibrated dentist, in accordance with the WHO guidelines. It was observed that 33% of GHD patients suffer from dental anomalies (hypodontia, microdontia or macrodontia), the difference between the study group and the control group was statistically significant (33% vs 4%, p < 0.001). Hypodontia and microdontia/macrodontia were the most common problems affecting 18% and 21% of the GHD individuals, respectively. The prevalence of DDE did not differ significantly between GHD group and the control group (58% vs 48%, p > 0.05). As children with GHD present more dental anomalies than their healthy coevals, clinicians should be aware of the possible oral health problems associated with GHD and consider dental screening and management as part of the patient’s overall health care plan.

The Growth Hormone Deficiency (GHD) Reversal Trial: effect on final height of discontinuation versus continuation of growth hormone treatment in pubertal children with isolated GHD—a non-inferiority Randomised Controlled Trial (RCT)

Background Growth hormone deficiency (GHD) is the commonest endocrine cause of short stature and may occur in isolation (I-GHD) or combined with other pituitary hormone deficiencies. Around 500 children are diagnosed with GHD every year in the UK, of whom 75% have I-GHD. Growth hormone (GH) therapy improves growth in children with GHD, with the goal of achieving a normal final height (FH). GH therapy is given as daily injections until adult FH is reached. However, in many children with I-GHD their condition reverses, with a normal peak GH detected in 64–82% when re-tested at FH. Therefore, at some point between diagnosis and FH, I-GHD must have reversed, possibly due to increase in sex hormones during puberty. Despite increasing evidence for frequent I-GHD reversal, daily GH injections are traditionally continued until FH is achieved.Methods/designEvidence suggests that I-GHD children who re-test normal in early puberty reach a FH comparable to that of children without GHD. The GHD Reversal study will include 138 children from routine endocrine clinics in twelve UK and five Austrian centres with I-GHD (original peak GH < 6.7 mcg/L) whose deficiency has reversed on early re-testing. Children will be randomised to either continue or discontinue GH therapy. This phase III, international, multicentre, open-label, randomised controlled, non-inferiority trial (including an internal pilot study) will assess whether children with early I-GHD reversal who stop GH therapy achieve non-inferior near FH SDS (primary outcome; inferiority margin 0.55 SD), target height (TH) minus near FH, HRQoL, bone health index and lipid profiles (secondary outcomes) than those continuing GH. In addition, the study will assess cost-effectiveness of GH discontinuation in the early retesting scenario.DiscussionIf this study shows that a significant proportion of children with presumed I-GHD reversal generate enough GH naturally in puberty to achieve a near FH within the target range, then this new care pathway would rapidly improve national/international practice. An assumed 50% reversal rate would provide potential UK health service cost savings of £1.8–4.6 million (€2.05–5.24 million)/year in drug costs alone. This new care pathway would also prevent children from having unnecessary daily GH injections and consequent exposure to potential adverse effects.Trial registrationEudraCT number: 2020-001006-39

Stunting and wasting in neurological Wilson disease: Role of copper, zinc, and insulin-like growth factor-I.

Copper (Cu) and zinc (Zn) are important trace elements for the growth and development of children. In Wilson disease (WD), impaired Cu metabolism may affect growth. This study was conducted to evaluate the height and weight of children with neurological WD and correlate these with serum Cu, Zn, and insulin-like growth factor-I (IGF-I). This prospective cohort study was conducted in a tertiary care teaching institute. Children with neurologic WD were included. The height, weight, and body-mass index of each child were measured and categorized according to the revised national growth chart. Serum Cu, Zn, calcium, alkaline phosphatase, albumin, thyroid-stimulating hormone, and urinary-Cu were measured. Serum IGF-1 was measured by enzyme-linked immunosorbent assay. The relationship between height and weight with trace elements and IGF was analyzed using parametric or non-parametric tests. There were 52 children (5-18 years) with neurologic WD. Thirty-six (69.2%) children had normal height, 12 (23.1%) were tall, and 4 (7.7%) were stunted. Forty-six (88.5%) children had normal weight and six (11.5%) children were underweight. IGF-1 correlated with height, weight, duration of treatment, and serum Zn level. About 15.4% of children had stunting and/or wasting, which was associated with low levels of serum IGF-I, Zn, and calcium. Stunting and/or wasting occurs in 15.4% of children with neurologic WD and is associated with reduced serum IGF-I, Zn, and calcium concentration. Adjunctive Zn and calcium treatment may help in achieving normal growth.

RANCANG BANGUN PROTOTYPE SISTEM INFORMASI PERINGATAN DINI DAN PENCEGAHAN BANJIR LUAPAN AIR SUNGAI BENDUNGAN PAMARAYAN BERBASIS INTERNET OF THINGS

This research will raise a system of how to plan an early warning system for floods in areas around rivers, or what is commonly called an Early Warning System (EWS) to prevent flooding around rivers. This early warning system is built with hardware that uses the ESP 32 microcontroller to control the level of water release from the dam and select the floodgates to be opened automatically. Ultrasonic sensors are used to detect water levels, IOT modules are used to provide quick information to officers. The object of this research was carried out at the Gerak Pamarayan Dam, a dam that controls the two largest rivers in Banten, namely Ciujung and Ciberang. Two rivers flow in two districts in the Banten area. The method used in this study is the Prototype method. And the expected result of this research is to create an early warning system for overflowing river water that measures the water level of the river automatically and automatically reports the water level that is at the threshold to the officers and what is equally important is that this system can also prevent flooding due to overflow by how to open the floodgates automatically when the river water level is beyond the normal height threshold.

Does different vertical position of maxillary central incisors in women with different facial vertical height affect smile esthetics perception?

BackgroundThe aim of this study was to assess the esthetic perceptions of orthodontists, prosthodontists and laypersons with regard to different vertical positions of the maxillary central incisors related to lateral incisors for different facial vertical height cases.Subject and methodsFrontal full-face photographs showing social smiles of three adult women aged between 18 and 25 years were used. Vertical position of the maxillary central incisor was changed (intruded or extruded) with 0.5 mm increments according to the reference gingival line resulting five images for each woman in a full-face view yielding a total of 15 images. A visual analog scale was placed below each smile to allow the raters to evaluate the attractiveness of each smile independently. One-way analysis of variance was used to determine whether there was a difference between more than two independent groups in terms of quantitative variables. Comparisons of more than two dependent groups were examined with repeated measures one-way ANOVA. The significance level was taken as 0.05 for all analyses.ResultsFor increased facial vertical height, the highest scores for orthodontists were given to the 0.5 mm extruded (64.18 ± 26.36), for prosthodontists to the control (57.28 ± 19.80), and for layperson to the 1 mm extruded (61.27 ± 25.98) central incisor position. For decreased facial vertical height, the highest scores were obtained at the 0.5 mm intrusion with an increasing pattern from orthodontists to laypersons (63.95 ± 22.08 for orthodontists, 79.87 ± 21.43 for prosthodontists, and 79.88 ± 19.17 for laypersons). All three rater groups gave the highest scores to the 0 mm (control) smile design for normal facial vertical height. When these scores were compared among the groups, laypersons gave significantly higher scores compared to orthodontists (p < 0.001) and prosthodontists (p = 0.005).ConclusionsThe facial vertical height significantly affected the perception of smile esthetics. Keeping the distance between the central and lateral incisors longer than 1 mm in individuals with increased facial height may be important in terms of increasing patient satisfaction in terms of clinical aesthetics. On the contrary, keeping the distance between the central and lateral incisors shorter than 1 mm may create a more esthetically acceptable result in individuals with short facial height.

Flood Scenario of Tigris River in Baghdad City

Flooding hazard is an important and dangerous natural phenomenon that leads to significant material losses. It should be studied and scenario to prevent significant losses. The studies should consider the impact of many factors such as human, infrastructure, economic,..etc. The main objective of the research is the risk management procedure. The study was conducted in Baghdad, Iraq. The materials for completing this research were prepared by gathering a satellite image and Digital Elevation Model (DEM) via the USGS website, then processed, analyzed, and converted into a different flood region concerning the probability of rising water levels where the normal height of Baghdad city is 28m over sea level. This scenario defines 3m, 4m, and 5m heights over the Tigris river cliff, which are the possible heights at which the water level may rise above the normal height. The range of the elevations becomes either 31m, 32m, or 33m over sea level. Many software’s were conducted in this research, such as MatLab, ArcGIS, and ENVI.

PENGARUH HEALTH EDUCATION DENGAN METODE AUDIOVISUAL TERHADAP PENGETAHUAN DAN SIKAP IBU DALAM UPAYA MENCEGAH STUNTING PADA ANAK PRASEKOLAH

Toddlers who have less height are characterized by delayed growth of children which results in failure to achieve normal and healthy height according to the child's age. This study aims to determine the effect of health education on knowledge and attitudes of mothers in an effort to prevent stunting in Kalikejambon Village, Tembelang District, Jombang Regency. The method used is delivering material and filling out questionnaires related to stunting prevention. The results of the study were obtained after being given education using the audiovisual method there was an increase in sufficient knowledge (64%) while a positive attitude (92%) in preventing stunting in preschoolers, with a p-value = 0.00 (p &lt;0.05) means that the accepted means that there is a significant effect after being given health education with the audiovisual method. It is hoped that with an increase in knowledge and attitude in mothers who have stunted children, it can reduce the incidence of stunting.

Gambaran Status Gizi Pada Pasien Tuberkulosis Paru (TB Paru) Usia 0-5 Tahun yang Menjalani Rawat Jalan di Poli Anak RSUD Cut Meutia Aceh Utara Tahun 2022

Tuberculosis (TB) is an infectious disease caused by the germ Mycobacterium tuberculosis, which can attack various organs, especially the lungs. This disease if not treated or treatment until complete it will cause dangerous complications until death. Objective: To determine the picture of nutritional status in Pulmonary TB patients aged 0-5 years who undergo outpatient treatment at the Children's Poly of RSUD Cut Meutia North Aceh in 2022. Method: This study is a descriptive research conducted from September 1, 2021 to August 31, 2022. Results: The age of respondents diagnosed with Pulmonary TB was at most 13-24 months and 49-60 months respectively (25%) with the highest sex of respondents being men (55%). Nutritional Status in the measurement of BB / U is the most with normal weight (50%), TB / U index obtained normal height (60%), BB / TB index and BMI / U have the most good nutritional status (65%). Conclusion: Variations in the nutritional status of pulmonary TB patients were obtained at the Children's Poly of RSUD Cut Meutia Aceh

Czech dysplasia mimicking rheumatoid arthritis: Case series andliterature review.

This study reported a family with most members affected by Czech dysplasia. We examined the patients' clinical, laboratory, and imaging characteristics and evaluated their functional capacity using the Stanford Health Assessment Questionnaire-Disability Index. The method used was case series description and literature review. This study showed that the pathogenic variant c.823C>T in the COL2A1 gene, which is a characteristic of Czech dysplasia, was found in 12 Brazilian individuals. Half of the patients in this family met the criteria for rheumatoid arthritis (RA) based on the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria. Patients had arthritis in their hand joints, synovitis detected by ultrasound, and alterations in inflammatory tests. The Stanford Health Assessment Questionnaire-Disability Index assessment revealed that all patients exhibited moderate-to-severe functional disability. What distinguish Czech dysplasia from RA are an autosomal dominant inheritance pattern, platyspondyly, sensorineural hearing loss, and shortening of the metatarsal bones. It is important to consider Czech dysplasia as a potential differential diagnosis for RA. This autosomal dominant skeletal dysplasia is associated with normal height, short metatarsals, platyspondyly, hearing loss, enlarged epiphyses, and precocious osteoarthritis. Inflammatory findings such as arthritis, synovitis, and alteration of inflammatory markers may also be present in individuals with Czech dysplasia.

Analysis of Pulpal Stress in Varied Orthodontic Tooth Movements at Different Bone Levels: A Finite Element Analysis

Aim To analyze the pulpal stress in varied orthodontic tooth movements at ideal force levels and different bone levels, and compare any differences in pulpal stress values between anterior and posterior teeth. Materials and Methods Four Finite Element Method models of incisor and molar teeth were simulated with normal bone height and 50% bone height. Each of these models was loaded with five different types of orthodontic tooth movements—Tipping, Translation, Intrusion, Extrusion, and Rotation. The ideal force levels simulated for each type of tooth movement were: Intrusion-20 g, Extrusion-60 g, Tipping-60 g, Translation-120 g, Rotation-60 g. The pulpal stress was evaluated at three levels—pulp chamber, pulp canal, and below root apex, so that we get three values of pulpal stress for anterior and posterior teeth, for each type of tooth movement and its corresponding force level. Results The results showed that in both incisor and molar models with normal bone height as well as 50% bone height, rotation gave the highest pulpal stress while translation gave the least. In both incisor and molar models with normal bone height as well as 50% bone height, pulpal stress was found out to be highest in the root apex region of the tooth. The stress values for incisor and molar models with 50% bone height were found to be almost double that of the models with normal bone height. The pulpal stress for incisor teeth was found to be greater than the molar teeth for all types of tooth movement. Conclusion The present findings indicate that the stress manifested below the root apex is highest. Rotational movements induce the highest stress and translational forces develop the lowest stress related to the physiologic capillary blood pressure. Furthermore, in situations with reduced periodontium, lower forces are needed to reach the maximum tolerable stress compared with teeth with intact periodontium.

Poster 245: Clinical Measurement of the Standard Q-Angle Correlates Poorly with Tibial Tuberosity to Trochlear Groove Distance in Awake Patients and Anesthetized Patients with Patella Alta and Trochlear Dysplasia

Objectives: The quadriceps angle (Q-angle) measures the force vector of pull of the extensor mechanism of the knee. A larger Q-angle is thought to be a predisposing factor for patellar dislocation, but previous literature has reported poor reliability and validity of clinically measured Q-Angle. In response to poor reliability, a new “Standard Q-Angle” (SQA) was developed by Merchant et al. (Merchant 2020) in an attempt to create a standardized and repeatable method of clinically measuring the Q-Angle. The SQA may be a practical, inexpensive, and valuable part of physical examinations to help clinicians decide if concomitant medializing osteotomy is indicated in patellar stabilization procedures. However, SQA has not yet been validated in patients with anatomic risk factors for recurrent patellar instability such as patella alta and trochlear dysplasia. Furthermore, while SQA has previously been demonstrated to have strong interrater reliability, it has never been shown to correlate with standardized measurements for a lateralized tibial tuberosity, such as the Tibial Tuberosity – Trochlear Grove (TT-TG) distance. Therefore, the purpose of our study was to determine the correlation between SQA and TT-TG distance in patients with recurrent patellar instability. We hypothesized that there would be a positive correlation between SQA and TT-TG distance. 1. Merchant AC, Fraiser R, Dragoo J, Fredericson M. A reliable Q angle measurement using a standardized protocol. Knee. 2020;27(3):934-939. Methods: Patients at a single institution treated by a single surgeon with recurrent patellar instability who had previously obtained a dynamic 4D CT scan were included in this study. Patients who had previous patellar stabilization procedures were excluded. The Standard Q-angle was measured as previously described by Merchant et al. (Merchant 2020). The patient was placed in the supine position with the knee extended. A long-arm goniometer was centered over the patella with the distal arm over the tibial tuberosity and the proximal arm extended up to the anterior superior iliac spine (ASIS). The examiner then centered the patella within the trochlear groove and the SQA was measured. A second examiner stood at foot of the patient’s bed to confirm positioning. Measurements were taken in the office, as well as in the operating room after the induction of general anesthesia. All measurements were performed by the senior author (***). Utilizing 4D CT scans, the TT-TG, Caton-Deschamps index (CDI), and lateral trochlear inclination (LTI) were measured as previously described. Patients whose CDIs were between 0.8 and 1.2 were considered to have normal patellar height. Patients whose LTIs were &gt;11° were considered to have normal LTI, which has been shown to have a sensitivity of 93% and a specificity 87% for detecting trochlear dysplasia. Mean and standard deviation values were calculated for patient demographic information, and correlation coefficients were calculated to compare SQA with TT-TG distance in both awake and anesthetized patients. The statistical software Stata was utilized for all analyses (StataCorp. 2021. Stata Statistical Software: Release 17. College Station, TX). Results: Fifty-seven patient knees were included in the study. The mean age was 22 years-old (±6 years). For awake patients, the correlation coefficient (R2) between SQA and TT-TG was -0.006 (Figure 1), and in anesthetized patients R2 = 0.093 (Figure 2). In the “normal patellar height” group, the R2 value was higher in the anesthetized group (R2 = 0.334) than the awake group (R2 = 0.239). In the normal lateral trochlear inclination group, there was also a greater R2 value in the anesthetized group (R2 = 0.403) than the awake group (R2 =0.093). The correlation between SQA and TT-TG was the strongest in anesthetized patients with both a CDI &lt; 1.2 and LTI &gt;11° (R2 = 0.635). Conclusions: There was a strong positive association between SQA and TT-TG in anesthetized patients with normal patellar height and a normal lateral trochlear inclination. However, in awake patients and patients with anatomic risk factors for recurrent patellar instability there was only a weak association between SQA and TT-TG. The SQA may be able to provide useful information, but only in selected cases. Therefore, it remains important to have objective radiographic measurements to characterize the position of the tibial tuberosity when planning patellar stabilization surgery.