Body Mass Index Distributions and Obesity Prevalence in a Transgender Youth Cohort - A Retrospective Analysis.

PURPOSE: To evaluate differences in auxological parameters between transgender and cisgender adolescents. METHODS: Retrospective analysis of auxological data of 269 transgender and gender diverse patients (75% assigned female at birth or AFAB, 25% assigned male at birth or AMAB) at the outpatient clinic for Pediatric Endocrinology at the Vienna General Hospital. All were treatment naïve at initial measurement. Height and weight data were compared to current World Health Organization (WHO) standards, defining a standard deviation score (SDS) of ≥ 1 ≤ 2 as overweight and > 2 as obese. RESULTS: In our untreated transgender population (mean age 15.7 years), 20% were overweight and 17% obese. Mean BMI was 0.64 SDS above the WHO average (p < .001). This result was more pronounced in the AFAB subgroup (+0.73 SDS, p < .001) than in the AMAB group (+0.37 SDS, p = .07). The AMAB group showed markedly higher BMI variance compared to WHO standards (p < .001) and to the AFAB group (p = .03), due to a higher relative number of underweight observations. When correcting for psychiatric diagnosis, transgender patients were still significantly overweight (p < .001). In patients for whom data both pregender-affirming hormone therapy and during gender-affirming hormone therapy was available (n = 133), BMI SDS did not change significantly over time (p = .22). DISCUSSION: We observed significantly higher rates of overweight and obesity in our adolescent transgender cohort. The reasons are likely complex and multifactorial. This makes eating and exercise behaviors central in both transgender care and future research.

Treatment trajectories of gender incongruent Austrian youth seeking gender-affirming hormone therapy.

Objective: The aim of this study was to describe the treatment trajectories of Austrian children and adolescents with gender incongruence seeking gender-affirming medical care. Methods: Patients who presented with gender incongruence at the pediatric outpatient clinic for differences in sex development at a large university hospital in Austria from January 2008 to December 2022 were included in a retrospective chart review, and analyzed regarding referral numbers, patient characteristics, treatment trajectories, fertility preservation, and legal gender marker changes. Results: Of 310 eligible patients, 230 (74.2%) were assigned female at birth (AFAB), and 80 (25.8%) were assigned male at birth (AMAB). The number of referrals increased steeply from 2008 to 2018, whereafter it stabilized at around 50 per year. At the time of initial presentation, the median age of patients was 15.6 years (IQR 14.3-16.8). AMAB individuals tended to be younger (median 14.9 years, IQR 13.9-16.8) than AFAB individuals (median 15.8 years, IQR 14.4-16.8; p= 0.012). 207 (66,8%) completed the assessment process and were eligible for gender affirming medical treatment (GAMT). Of those, 89% (186/207) commenced gender affirming hormone therapy in the pediatric outpatient clinic (79/186 received GnRHa monotherapy, 91/186 GnRHa and sex steroids, and 16/186 sex steroid monotherapy). Of the 54 AMAB individuals receiving GAMT, 6 (11.1%) completed fertility preservation prior to therapy initiation. Only 1/132 AFAB adolescents receiving GAMT completed fertility preservation. Chest masculinization surgery was performed in 22 cases (16.7%), and breast augmentation in two cases (3.7%) between the ages of 16 and 18. Changes in legal gender marker were common, with 205 individuals (66.1%) having changed their legal gender marker. Conclusion: This is the first time that treatment trajectories, fertility preservation rates, and changes of legal gender marker have been described in Austrian adolescents with gender incongruence seeking GAMT. The majority received GAMT and changed their legal gender marker, while gender affirming surgery rates were low, and utilization of fertility preservation treatment options was rare.

Mental Health of Transgender Youth: A Comparison of Assigned Female at Birth and Assigned Male at Birth Individuals.

Gender dysphoric adolescents report a gender identity which is incongruent with their assigned sex at birth, whereby the experienced incongruence is accompanied by clinically relevant distress. The aim of the study was to assess and compare the mental health of transgender youth by assigned sex at birth. A total of n = 49 adolescents (n = 29 assigned females at birth, n = 20 assigned male at birth) aged 12 to 18 years with the diagnosis of gender dysphoria according to DSM-5 were included in the study. The adolescents underwent a psychological assessment in a child and adolescent psychiatry outpatient department prior to starting gender-affirming medical treatment, completing relevant mental health questionnaires. Although no differences were found in psychiatric disorders, more externalizing problems above the clinical threshold were reported by parents in assigned female at birth (AFAB) adolescents. On the other hand, internalizing problems, both in general and within the clinical range, were found to be more prevalent in assigned male at birth (AMAB) adolescents, as indicated by self-report. Our results suggest that a comprehensive assessment of mental health in gender dysphoric adolescents is crucial for understanding the diverse range of challenges they may face and tailoring appropriate interventions to address their specific needs.

Impact of Newborn Screening on Adult Height in Patients With Congenital Adrenal Hyperplasia (CAH).

CONTEXT: Treatment of children with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is challenging. Linear growth and adult height are compromised according to recent publications. However, most of these data were obtained in the era before CAH newborn screening. DESIGN: Body height of patients with classical CAH diagnosed before and after the establishment of newborn screening were analyzed retrospectively. PATIENTS AND METHODS: We identified 600 patients with classical CAH (227 male) with data on near-adult height (NAH), target height (TH), and information on newborn screening from the electronic German CAH registry (German Society for Paediatric Endocrinology and Diabetology). Newborn screening was performed in 101 (16.8%) patients. All patients received hydrocortisone with or without fludrocortisone.To assess the effects of newborn screening, a linear regression model adjusted/stratified for sex and phenotype was used (SAS 9.4). RESULTS: TH corrected NAH (mean; 95% confidence interval) was closer to 0 in patients with CAH and newborn screening [-0.25 standard deviation score (SDS); -0.44 to -0.06] than in patients without newborn screening (-0.44 SDS; -0.52 to -0.36) (P = .069). Screening had no effect on NAH in female patients. In male patients, NAH was significantly better (P = .033) with screening than without screening. After stratifying for CAH phenotype, screening did not affect the NAH of patients with salt-wasting CAH. Patients with simple-virilizing CAH had a significantly better cNAH (P = .034) with screening (0.15 SDS; -0.28-0.59) than without screening (-0.35 SDS; -0.52 to -0.18). CONCLUSIONS: Our data suggest that newborn screening might be associated with improved NAH in male CAH patients and in patients with simple-virilizing CAH.

Lipidation and PEGylation Strategies to Prolong the in Vivo Half-Life of a Nanomolar EphA4 Receptor Antagonist.

The EphA4 receptor tyrosine kinase plays a role in neurodegenerative diseases, inhibition of nerve regeneration, cancer progression and other diseases. Therefore, EphA4 inhibition has potential therapeutic value. Selective EphA4 kinase inhibitors are not available, but we identified peptide antagonists that inhibit ephrin ligand binding to EphA4 with high specificity. One of these peptides is the cyclic APY-d3 (ßAPYCVYRßASWSC-NH2), which inhibits ephrin-A5 ligand binding to EphA4 with low nanomolar binding affinity and is highly protease resistant. Here we describe modifications of APY-d3 that yield two different key derivatives with greatly increased half-lives in the mouse circulation, the lipidated APY-d3-laur8 and the PEGylated APY-d3-PEG4. These two derivatives inhibit ligand induced EphA4 activation in cells with sub-micromolar potency. Since they retain high potency and specificity for EphA4, lipidated and PEGylated APY-d3 derivatives represent new tools for discriminating EphA4 activities in vivo and for preclinical testing of EphA4 inhibition in animal disease models.

Effects of the short stitch technique for midline abdominal closure on incisional hernia (ESTOIH): randomized clinical trial.

BACKGROUND: Incisional hernia remains a frequent problem after midline laparotomy. This study compared a short stitch to standard loop closure using an ultra-long-term absorbent elastic suture material. METHODS: A prospective, multicentre, parallel-group, double-blind, randomized, controlled superiority trial was designed for the elective setting. Adult patients were randomly assigned by computer-generated sequence to fascial closure using a short stitch (5 to 8 mm every 5 mm, USP 2-0, single thread HR 26 mm needle) or long stitch technique (10 mm every 10 mm, USP 1, double loop, HR 48 mm needle) with a poly-4-hydroxybutyrate-based suture material (Monomax®). Incisional hernia assessed by ultrasound 1 year after surgery was the primary outcome. RESULTS: The trial randomized 425 patients to short (n = 215) or long stitch technique (n = 210) of whom 414 (97.4 per cent) completed 1 year of follow-up. In the short stitch group, the fascia was closed with more stitches (46 (12 s.d.) versus 25 (7 s.d.); P < 0.001) and higher suture-to-wound length ratio (5.3 (2.2 s.d.) versus 4.0 (1.3 s.d.); P < 0.001). At 1 year, seven of 210 (3.3 per cent) patients in the short and 13 of 204 (6.4 per cent) patients in the long stitch group developed incisional hernia (odds ratio 1.97, 95 per cent confidence interval 0.77 to 5.05; P = 0.173). CONCLUSION: The 1-year incisional hernia development was relatively low with clinical but not statistical difference between short and long stitches. Registration number: NCT01965249 (http://www.clinicaltrials.gov).

Endocrine outcome and seminal parameters in young adult men born with hypospadias: A cross-sectional cohort study.

BACKGROUND: Hypospadias affects around 1/200 newborn males. Intrauterine testicular dysfunction may underlie a subset of cases. The long-term endocrine and reproductive outcomes in these men remain largely unknown. METHODS: Cross-sectional study in Ghent and Vienna University Hospitals to assess the endocrine and seminal parameters of young adult men (16-21 years) born with non-syndromic hypospadias (NSH) (n = 193) compared to healthy typical males (n = 50). Assessments included physical exam, semen analysis, hormone assays and exome-based gene panel analysis (474 genes). FINDINGS: All participants had experienced a spontaneous puberty, in spite of higher LH and INSL3 levels than typical males. Oligo- or azoospermia was observed in 32/172 (18·6%; 99%-CI: 12·2-27·4%) of NSH men; but in 5/16 (31·3%; 99%-CI: 11·1;62·4%) of complex NSH men and in 13/22 (59·1%; 99%-CI: 33·2-80·7%) of those born small for gestational age (SGA). No (likely) pathogenic coding variants were found in the investigated genes. Suboptimal statural growth affected 8/23 (34·8%; 99%-CI: 15·4-61·0%) of men born SGA with NSH. INTERPRETATION: Spermatogenesis is significantly compromised in NSH men, especially in those born SGA or those with complex NSH. Long-term andrological follow-up is recommended, including end-pubertal semen analysis. No clear monogenic causes could be demonstrated in our cohort even in proximal or complex NSH. Being born SGA with NSH is frequently associated with poor catch-up growth, requiring growth hormone therapy in some. FUNDING: Research grants from the European Society of Paediatric Endocrinology, the Belgian Society of Pediatrics, the Belgian Society of Pediatric Endocrinology and Diabetology and the Research Foundation Flanders (FWO).

[Emergency card, emergency medication, and information leaflet for the prevention and treatment of adrenal crisis (Addison crisis): an Austrian consensus document]. / Notfallausweis, Notfallmedikation und Informationsmaterial zur Prävention und Therapie der Nebennierenkrise (Addison-Krise): Ein österreichisches Konsensusdokument.

A central goal of the adrenal insufficiency management is the prevention of acute adrenal insufficiency (also known as adrenal crisis or Addison crisis). This consensus document was generated in order to achieve better implementation and harmonization of measures for the prevention and treatment of acute adrenal insufficiency in Austria. The following measures are generally recommended for all patients with adrenal insufficiency and are outlined in this manuscript: (1) Provision of a "steroid emergency card" and possibly also a medical alert bracelet or necklace (or similar identification). (2) Provision of a hydrocortisone injection kit (or alternative glucocorticoid preparations) for emergency use plus sufficient oral glucocorticoid doses for stress situations/illness. (3) Education of patients and relatives on glucocorticoid stress dosing and "sick day rules" as well as on self-injection of hydrocortisone. (4) Provision of a treatment guideline (information leaflet) for the prevention and therapy of the adrenal crisis, which should also be shown to healthcare staff if necessary. (5) Provision of an emergency phone number (contact details) of the responsible endocrine specialist team or other trained staff. (6) Reinforcement of patient education on a regular basis (preferably yearly). This consensus document also includes recommendations for glucocorticoid dosing in the perioperative setting as well as in various other stress situations.

Growth, puberty and testicular function in boys born small for gestational age with a nonspecific disorder of sex development.

OBJECTIVE: Being born small for gestational age (SGA) is frequently associated with unexplained disorders of sex development (nonspecific DSD) in boys. Little is known about their future growth, puberty and testicular function. Our objective is to determine the long-term endocrine outcome of boys born SGA who have a nonspecific DSD. DESIGN: Boys with a nonspecific DSD born SGA and appropriate for GA (AGA) were retrieved through the International Disorders of Sex Development registry and retrospective data collected, based on a spreadsheet containing 102 items. PATIENTS AND MEASUREMENTS: In total, 179 boys were included, of which 115 were born SGA and 64 were born AGA. Their growth and pubertal development were compared. Serum LH, FSH, testosterone, AMH and inhibin B levels in infancy and puberty were analysed to assess testicular function. RESULTS: At 2 years of age, 30% of SGA boys had incomplete or absent catch-up growth. Boys born SGA also had higher LH during minipuberty and lower testosterone in stimulation tests (p = 0.037 and 0.040, respectively), as compared to boys born AGA. No differences were observed in timing or course of puberty or end-pubertal hormone levels. CONCLUSIONS: Almost one out of three SGA boys with a nonspecific DSD experiences insufficient catch-up growth. In addition, our data suggest dysfunction of infantile Leydig cells or altered regulation of the hypothalamic-pituitary-gonadal axis in SGA boys during childhood. Sex steroid production during puberty seems unaffected.

Adolescent and Young Adult Urogenital Outcome following Childhood Hypospadias Repair: Perfection Revisited.

PURPOSE: We assessed the long-term surgical, functional urinary and sexual outcomes of adolescent and young adult men who underwent childhood hypospadias repair. MATERIALS AND METHODS: Men born with nonsyndromic hypospadias and healthy male controls aged 16-21 years old were recruited, and their surgical, urinary, sexual functional and aesthetic outcomes assessed. Good outcome was defined as a patent and orthotopic meatus without fistulas, and straight erections (<30 degree curvature) without erectile or ejaculatory problems. Statistics included regression analyses, chi-square/Fisher exact tests and Student's t/Mann-Whitney U and Kruskal-Wallis tests. RESULTS: A total of 193 patients and 50 controls participated 16.4 years (range 8.2-21.2) after initial repair. At least 1 reintervention was performed in 39.2%. The highest reintervention rate was found in those younger than 12 months at initial repair, even when excluding proximal hypospadias cases. A disturbed urinary and/or suboptimal sexual functional outcome was seen in 52.9% of cases. Suboptimal voiding was found in 22.1%, although few had relevant residual urine. More reinterventions and proximal hypospadias cases were associated with suboptimal urinary outcome, and the latter also with impaired sexual function. Poor inter-observer agreements were found between physician and patient genital appraisal. CONCLUSIONS: In 52.9% of cases, at least 1 concern was identified that required long-term followup. Hypospadias repair below 12 months was associated with more reinterventions. Adopting a restrictive attitude toward aesthetic refinement, unless on the patient's own request, could improve urinary outcomes.

Hydrocortisone dosing in children with classic congenital adrenal hyperplasia: results of the German/Austrian registry.

OBJECTIVE: Treatment of classic congenital adrenal hyperplasia (CAH) is necessary to compensate for glucocorticoid/mineralocorticoid deficiencies and to suppress androgen excess. Hydrocortisone (HC) is preferred in growing children with classic CAH but recommendations regarding dosage/administration are inconsistent. The aim of this study was to evaluate HC dosing in children with CAH in relation to chronological age, sex, and phenotype based on a multicenter CAH registry. DESIGN: The CAH registry was initiated in 1997 by the AQUAPE in Germany. On December 31st 2018, data from 1571 patients were included. METHODS: A custom-made electronic health record software is used at the participating centers. Pseudonymized data are transferred for central analysis. Parameters were selected based on current guidelines. Descriptive analyses and linear regression models were implemented with SAS 9.4. RESULTS: We identified 1288 patients on exclusive treatment with hydrocortisone three times daily (604 boys; median age 7.2 years; 817 salt-wasting phenotype, 471 simple-virilizing phenotype). The mean (lower-upper quartiles) daily HC dose (mg/m² body surface area) was 19.4 (18.9-19.8) for patients <3 months (n = 329), 15.0 (14.6-15.3) for age ≥3-12 months (n = 463), 14.0 (13.7-14.3) for age 1-5.9 years (n = 745), 14.2 (14.0-14.5) for age 6 years to puberty entry (n = 669), and 14.9 (14.6-15.2) during puberty to 18 years (n = 801). Fludrocortisone was administered in 74.1% of patients with a median daily dosage of 88.8 µg. CONCLUSION: Our analyses showed that still a high proportion of children are treated with HC doses higher than recommended. This evaluation provides comprehensive information on nationwide hydrocortisone substitution dosages in children with CAH underlining the benefit of systematic data within a registry to assess daily practice.

Diagnostic Value of Serum Acid-Labile Subunit Alone and in combination with IGF-I and IGFBP-3 in the Diagnosis of Growth Hormone Deficiency.

BACKGROUND: The acid-labile subunit (ALS) is a crucial factor in the tertiary complex. IGF-I and IGFBP-3 are routinely measured during the diagnostic work-up for growth hormone deficiency (GHD). The aim of the study is to evaluate the relevance of serum ALS as an additional biomarker in the diagnosis of GHD. METHODS: Ninety-one children undergoing standard diagnostic work-up for GHD were included in this retrospective study. Inclusion criteria were evidence-based auxological cutoffs, IGF-I and IGFBP-3 <-2 SDS at first presentation, at least 1 growth hormone (GH) stimulation test, and IGF-I, IGFBP-3, and ALS measurements on the same day. Statistical analysis was performed by ROC as well as by odds ratio calculations. RESULTS: Forty-seven of 90 participants presented with peak GH values under the cutoff of 7 ng/mL. AUC from a model containing only IGF-I was 0.76 and 0.68 when using only ALS. A model containing IGF-I, IGFBP-3, and ALS (AUC = 0.77) did not improve the result compared to the combination of IGF-I/IGFBP-3 (0.77) or IGF-I/ALS (0.76). Furthermore, the variation in the outcome (GH peak

Psychosexual Outcome, Sexual Function, and Long-Term Satisfaction of Adolescent and Young Adult Men After Childhood Hypospadias Repair.

BACKGROUND: The psychosexual outcome in adolescents and young adults (AYA) men born with hypospadias is precarious. However, the factors responsible for impaired outcome in some AYA men have been understudied. AIM: To explore the outcome after hypospadias repair in childhood of AYA men aged 16-21 years and examine their opinion and their parents' opinion about this type of surgery. METHODS: Cross-sectional assessment of 193 AYA men born with hypospadias and 50 male controls was performed. Questionnaires such as the Decision Regret Scale, Pediatric Penile Perception Score, Sexual Quality of Life-Male, International Index of Erectile Function, and a custom-made questionnaire were used. The Decision Regret Scale and a custom-made questionnaire were also completed by the participants' parents. Physical examination including Hypospadias Objective Penile Evaluation and measuring stretched penile length was performed. OUTCOMES: This study reports the psychosexual functioning (ie, social, relational, and sexual), erectile and sexual function after childhood hypospadias repair, using ad hoc measures. In addition, the opinion about hypospadias repair of patients and their parents is represented. RESULTS: The number of surgeries and satisfaction regarding penile appearance were the most important factors associated with the opinion on hypospadias repair and the psychosexual outcome. Most AYA men were more satisfied with their penile appearance than the physician. 80% of men were satisfied with having had a childhood hypospadias repair, even though they had not been able to consent to surgery themselves. Erectile and ejaculation problems were mild and seen in approximately 10% of the population. CLINICAL IMPLICATIONS: Based on our data, deferring hypospadias repair until the patient can decide himself is not warranted. However, physicians who accept a suboptimal esthetic outcome and withdraw from repeated surgery may contribute importantly to the patient's well-being, especially in proximal forms of hypospadias. STRENGTHS & LIMITATIONS: This is one of the rare studies addressing the AYA's psychosexual outcome after childhood hypospadias repair. Strengths include the combination of clinical and psychosexual data from a very large cohort of men and their parents to provide a more holistic view. By entering this study, participants might have a different comfort level regarding their sexuality or have a different body image than the overall population of young men. CONCLUSION: Uncomplicated hypospadias surgery results in equal psychosexual outcome as controls and in high satisfaction rates; multiple surgeries are a risk factor for poorer outcomes. 80% of men are satisfied with childhood hypospadias repair. Tack LJW, Springer A, Riedl S, et al. Psychosexual Outcome, Sexual Function, and Long-Term Satisfaction of Adolescent and Young Adult Men After Childhood Hypospadias Repair. J Sex Med 2020;17:1665-1675.

Analysis of variants in GATA4 and FOG2/ZFPM2 demonstrates benign contribution to 46,XY disorders of sex development.

BACKGROUND: GATA-binding protein 4 (GATA4) and Friend of GATA 2 protein (FOG2, also known as ZFPM2) form a heterodimer complex that has been shown to influence transcription of genes in a number of developmental systems. Recent evidence has also shown these genes play a role in gonadal sexual differentiation in humans. Previously we identified four variants in GATA4 and an unexpectedly large number of variants in ZFPM2 in a cohort of individuals with 46,XY Differences/Disorders of Sex Development (DSD) (Eggers et al, Genome Biology, 2016; 17: 243). METHOD: Here, we review variant curation and test the functional activity of GATA4 and ZFPM2 variants. We assess variant transcriptional activity on gonadal specific promoters (Sox9 and AMH) and variant protein-protein interactions. RESULTS: Our findings support that the majority of GATA4 and ZFPM2 variants we identified are benign in their contribution to 46,XY DSD. Indeed, only one variant, in the conserved N-terminal zinc finger of GATA4, was considered pathogenic, with functional analysis confirming differences in its ability to regulate Sox9 and AMH and in protein interaction with ZFPM2. CONCLUSIONS: Our study helps define the genetic factors contributing to 46,XY DSD and suggests that the majority of variants we identified in GATA4 and ZFPM2/FOG2 are not causative.

Clinical but Not Histological Outcomes in Males With 45,X/46,XY Mosaicism Vary Depending on Reason for Diagnosis.

CONTEXT: Larger studies on outcomes in males with 45,X/46,XY mosaicism are rare. OBJECTIVE: To compare health outcomes in males with 45,X/46,XY diagnosed as a result of either genital abnormalities at birth or nongenital reasons later in life. DESIGN: A retrospective, multicenter study. SETTING: Sixteen tertiary centers. PATIENTS OR OTHER PARTICIPANTS: Sixty-three males older than 13 years with 45,X/46,XY mosaicism. MAIN OUTCOME MEASURES: Health outcomes, such as genital phenotype, gonadal function, growth, comorbidities, fertility, and gonadal histology, including risk of neoplasia. RESULTS: Thirty-five patients were in the genital group and 28 in the nongenital. Eighty percent of all patients experienced spontaneous pubertal onset, significantly more in the nongenital group (P = 0.023). Patients were significantly shorter in the genital group with median adult heights of 156.7 cm and 164.5 cm, respectively (P = 0.016). Twenty-seven percent of patients received recombinant human GH. Forty-four patients had gonadal histology evaluated. Germ cells were detected in 42%. Neoplasia in situ was found in five patients. Twenty-five percent had focal spermatogenesis, and another 25.0% had arrested spermatogenesis. Fourteen out of 17 (82%) with semen analyses were azoospermic; three had motile sperm. CONCLUSION: Patients diagnosed as a result of genital abnormalities have poorer health outcomes than those diagnosed as a result of nongenital reasons. Most patients, however, have relatively good endocrine gonadal function, but most are also short statured. Patients have a risk of gonadal neoplasia, and most are azoospermic, but almost one-half of patients has germ cells present histologically and up to one-quarter has focal spermatogenesis, providing hope for fertility treatment options.

[Children's Rights in Health Care: The Views of Ombudsman Offices for Children and Youth and Patient Advocacies in Austria]. / Kinderrechte im Gesundheitswesen ­ die Sicht der Kinder- und Jugendanwaltschaften und der Patientenanwaltschaften in Österreich.

AIM: The aim of the survey was to obtain a rough estimate of the number and type of reported violations of children's rights in the health care system, as well as an expert evaluation of the problem by the responsible institutions. METHODS: A written survey of all Austrian Ombudsman offices for Children and Youth (OCYs) and Patient Advocacy offices (PAs) asked for the number and type of potential violations of children's rights and their significance. RESULTS: Both institutions are consulted very rarely regarding children's rights in health care. OCYs report a higher awareness about children's rights, even though health care issues are legally incorporated in the PA offices. PAs report incoming complaints regarding children's health care even less often. Cooperation between the 2 institutions is insufficient. Participation rights/consent issues and health care service deficiencies have been identified as the main children's rights problems. CONCLUSIONS: The low number of reported complaints as well the available literature indicates an insufficient awareness of supporting services and institutions for children's rights in health care in Austria. There is room for improvement in this area with more intensive cooperation between the responsible institutions, remediation of deficiencies in care, improved communication, and training and further education of personnel.

Body mass index and height in 11- to 16-year-old Austrian students attending two different school types with divergent socioeconomic backgrounds.

BACKGROUND: In developed countries high socioeconomic status (SES) is associated with lower body mass index (BMI) and greater height compared with low SES. AIM: To investigate differences in BMI/height in adolescent students from two different school types with divergent SES backgrounds. METHODS: A total of 4579 students (2313 female), aged 11-16 years, attending either low SES vocation-directed secondary schools (VSS) or high SES secondary academic schools (AHS) were compared. Potential differences were investigated using ANCOVA models including sex, school type, geographical region and degree of urbanicity. RESULTS: At all ages between 11 and 16 years the BMI of students attending VSS was significantly higher than that of students attending AHS (mean +0.87kg/m2). The AHS students were on average taller (mean +0.93cm; p<0.001), without statistically significant age-specific differences. The taller height contributed to lower BMI by approximately 25%. Short stature, overweight and obesity were 2.3-fold, 1.8-fold and 2.5-fold, respectively more frequent in VSS than in AHS students. The BMI was higher in students in Vienna than in communities with >100,000 (p<0.001) and 20,000-100,000 (p=0.045) but similar to communities with <20,000 inhabitants. CONCLUSION: These findings suggest that differences in BMI and height between students reflect early SES-based grouping into school types according to the academic level of the schools they attend.

Functional analysis of novel desert hedgehog gene variants improves the clinical interpretation of genomic data and provides a more accurate diagnosis for patients with 46,XY differences of sex development.

BACKGROUND: Desert hedgehog (DHH) gene variants are known to cause 46,XY differences/disorders of sex development (DSD). We have identified six patients with 46,XY DSD with seven novel DHH gene variants. Many of these variants were classified as variants of uncertain significance due to their heterozygosity or associated milder phenotype. To assess variant pathogenicity and to refine the spectrum of DSDs associated with this gene, we have carried out the first reported functional testing of DHH gene variant activity. METHODS: A cell co-culture method was used to assess DHH variant induction of Hedgehog signalling in cultured Leydig cells. Protein expression and subcellular localisation were also assessed for DHH variants using western blot and immunofluorescence. RESULTS: Our co-culture method provided a robust read-out of DHH gene variant activity, which correlated closely with patient phenotype severity. While biallelic DHH variants from patients with gonadal dysgenesis showed significant loss of activity, variants found as heterozygous in patients with milder phenotypes had no loss of activity when tested with a wild type allele. Taking these functional results into account improved clinical interpretation. CONCLUSION: Our findings suggest heterozygous DHH gene variants are unlikely to cause DSD, reaffirming that DHH is an autosomal recessive cause of 46,XY gonadal dysgenesis. Functional characterisation of novel DHH variants improves variant interpretation, leading to greater confidence in patient reporting and clinical management.