OBJECTIVE:Management of 21-hydroxylase deficiency (21-OHD) congenital adrenal hyperplasia (CAH) in early infancy is challenging, with extent of variation in management unclear. DESIGN AND METHODS:Using the I-CAH Registry, we retrospectively reviewed management over the first 90 days of life of 154 infants with 21-OHD born in 2018-2023, across 33 centers in 18 countries. RESULTS:Of 154 infants (92 female, 62 male), 136 were diagnosed postnatally, with median (10th centile, 90th centile) presentation age of Day 4 (0, 20.8). At initial hospital discharge, median doses of hydrocortisone (HC), fludrocortisone (FC), and salt were 17 (11.4, 39.6) mg/m2/day, 100 (50, 200) mcg/day and 3.5 (1.6, 8.7) mmol/kg/day, and at Day 90 (D90) 14.5 (8.7, 24.1) mg/m2/day, 100 (50, 200) mcg/day, and 2.1 (1.0, 5.2) mmol/kg/day, respectively. Hyponatremia, hyperkalemia, and hypoglycemia were reported in 70.0%, 71.9%, and 13.0% of infants, respectively. At D90, hyponatremia and hyperkalemia were reported in 7.4% and 28.6%, respectively. At D90, BP measurements were recorded in 30.5%, amongst whom 31.9% had hypertension reported. Median total hospitalization duration over 90 days was 9 days (2, 24). Adrenal crises were associated with 40. 6% of hospitalization episodes. Percentages (males:females) of cases seen by a pediatric endocrinologist, psychologist, pediatric endocrine nurse specialist, and surgeon by D90 were 95.9% (58:84), 33.3% (9:35), 42.1% (20:36), and 23.8% (0:35), respectively. CONCLUSIONS:Contemporary management of CAH in early infancy varies considerably. Hypertension and hyperkalemia are frequently reported. Our data may help inform development of quality indicators for benchmarking CAH care in infancy.

Silver-Russell syndrome (SRS) is a complex multisystem condition requiring timely diagnosis for appropriate management. A clinical diagnosis is made in individuals scoring ≥ 4 Netchine-Harbison Clinical Scoring System (NH-CSS) criteria, with (epi)genetic investigations undertaken in those with NH-CSS ≥ 3 and strong clinical suspicion. Monogenic variants in imprinted (CDKN1C and IGF2) and non-imprinted (HMGA2 and PLAG1) genes are recognised as rare causes of SRS. The frequency of associated phenotypes is unclear. We evaluated the suitability of SRS as an umbrella term for these (epi)genotypes by identifying key clinical features and assessing the validity of NH-CSS. An extensive literature search identified 22 IGF2, 18 HMGA2, 11 CDKN1C and 11 PLAG1 published reports. Clinical phenotypes including the NH-CSS criteria were interrogated to assess (dis)similarity between the molecular subgroups of SRS. Strict adherence to the NH-CSS identified clinical SRS in 91

Silver-Russell syndrome (SRS) is a clinical diagnosis requiring the fulfillment of ≥ 4/6 Netchine-Harbison Clinical Scoring System (NH-CSS) criteria. A score of ≥ 4/6 NH-CSS (or ≥ 3/6 with strong clinical suspicion) warrants (epi)genetic confirmation, identifiable in ∼60% patients. The approach to the investigation and diagnosis of SRS is detailed in the only international consensus guidance, published in 2016. In the intervening years, the clinical, biochemical, and (epi)genetic characteristics of SRS have rapidly expanded, largely attributable to advancing molecular genetic techniques and a greater awareness of related disorders. The most common etiologies of SRS remain loss of methylation of chromosome 11p15 (11p15LOM) and maternal uniparental disomy of chromosome 7 (upd(7)mat). Rarer causes of SRS include monogenic pathogenic variants in imprinted (CDKN1C and IGF2) and non-imprinted (PLAG1 and HMGA2) genes. Although the age-specific NH-CSS can identify more common molecular causes of SRS, its use in identifying monogenic causes is unclear. Preliminary data suggest that NH-CSS is poor at identifying many of these cases. Additionally, there has been increased recognition of conditions with phenotypes overlapping with SRS that may fulfill NH-CSS criteria but have distinct genetic etiologies and disease trajectories. This group of conditions is frequently overlooked and under-investigated, leading to no or delayed diagnosis. Like SRS, these conditions are multisystemic disorders requiring multidisciplinary care and tailored management strategies. Early identification is crucial to improve outcomes and reduce the major burden of the diagnostic odyssey for patients and families. This article aims to enable clinicians to identify key features of rarer causes of SRS and conditions with overlapping phenotypes, show a logical approach to the molecular investigation, and highlight the differences in clinical management strategies.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Childhood osteoporosis leads to increased propensity to fracture, and thus is an important cause of morbidity, pain and healthcare utilisation. Osteoporosis in children may be caused by a primary bone defect or secondary to an underlying medical condition and/or its treatment. Primary osteoporosis is rare, but there is an increasing number of children with risk factors for secondary osteoporosis. Therefore it is imperative that all paediatricians are aware of the diagnostic criteria and baseline investigations for childhood osteoporosis to enable timely referral to a specialist in paediatric bone health. This review will discuss the approach to diagnosis, investigation and management of childhood osteoporosis, with particular consideration to advances in molecular diagnosis of primary bone disorders, and current and emerging therapies for fracture reduction.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

A term Caucasian neonate with an uncomplicated birth history presented with persistent umbilical stump bleeding unresponsive to extensive topical haemostatic measures initially. He subsequently developed hypovolaemic shock. Routine full blood count and basic coagulation screen were unremarkable. He received packed red cell and cryoprecipitate transfusions. Further specialist coagulation studies performed revealed factor XIII deficiency. Genetic investigations demonstrated a compound heterozygosity for the disorder. He was later started on monthly prophylactic treatment of plasma-derived factor XIII. Clinicians should have a high index of suspicion for factor XIII deficiency for newborns with abnormal umbilical stump bleeding in the presence of no bleeding risk factors and normal routine blood investigations.

The genetic cause of 46, XY disorder of sex development (DSD) still cannot be determined in about half of the cases. GATA-4 haploinsufficiency is one of the rare causes of DSD in genetic males (46, XY). Twenty-two cases with 46, XY DSD due to GATA-4 haploinsufficiency (nine missense variant, two copy number variation) have been previously reported. In these cases, the phenotype may range from a mild undervirilization to complete female external genitalia. The haploinsufficiency may be caused by a sequence variant or copy number variation (8p23 deletion). The aim of this study was to present two unrelated patients with DSD due to GATA-4 variants and to review the phenotypic and genotypic characteristics of DSD cases related to GATA-4 deficiency.

ACAN variants can manifest as various clinical features, including short stature, advanced bone age (BA), and skeletal defects. Here, we report rare clinical manifestations of ACAN defects in a 9 year, 5 month-old girl born small for gestational age (SGA), who presented with short stature, and was initially diagnosed with idiopathic growth hormone deficiency. She displayed several dysmorphic features, including genu valgum, cubitus valgus, and recurrent patellar dislocations. She presented with progressive advancement of BA compared with chronological age. Whole exome sequencing confirmed the presence of a novel heterozygous nonsense variant, c.1968C>G, p.(Tyr656*), in ACAN. ACAN variants should be considered in short stature patients born SGA with joint problems, particularly those with recurrent patellar dislocation and genu valgum.

Aim To determine the prevalence and risk factors of ear disease in Turner syndrome (TS), propose an algorithm for future surveillance and recommend preventative strategies. Methods Review of TS patients seen in the West of Scotland between 1989 and 2015, with questionnaire follow-up in 2015. Results Of 168 girls, median age 27.3 (3.8-47.2) years, ear problems occurred more frequently with 45,X and 45,X/46,XiXq than other karyotypes: 71/103 (69%) versus 23/65 (35%). Recurrent acute otitis media (AOM) first developed at 0-5 years in 23 (40%) girls, persisting in 16 (10%) at 5-10 years; and first developing at 5-10 years in 11 (7%). Persistent otitis media with effusion (OME) first developed at 0-5 and 5-10 years in 23 (40%) and 14 (8%) girls. Recurrent AOM was significantly linked with cholesteatoma in 8 (4.9%) girls (7 aged >10 years). Permanent hearing loss was documented in 28 girls (16.7%), with 16 (9.5%) receiving hearing aids (bone-anchored in 3). Conclusion Acute otitis media and OME occur commonly in preschool TS girls and may persist or newly develop in later childhood. Recurrent AOM predisposes to cholesteatoma. Strategies to reduce otological morbidity include: intensive patient education, annual audiology, vaccinations and a randomised trial of antibiotic prophylaxis in high-risk groups.

A healthy 3-year-old girl presented with a 5-day history of right-sided cheek and eye swelling and pain, associated with right-sided green nasal discharge. Examination revealed diffuse erythematous swelling around the right cheek, jawline and eye. Oral antibiotics for suspected periorbital cellulitis were ineffective. Blood inflammatory markers and ultrasound of her neck and parotid glands were normal. She was discharged as having viral parotitis. Antibiotics and nasal drops were later restarted for clinical sinusitis; however, she showed no improvement, now having 3 weeks of right-sided facial swelling …

Aim: Implantation of a permanent sacral nerve stimulation (SNS) device is reserved for patients who have demonstrated benefit during testing and patients selected for implantation must have shown a minimum level of understanding with the technology. The hypothesis behind this study was that the Scottish SNS for Urinary Dysfunction service unknowingly selected patients from higher socioeconomic classes, who seemed more likely to manage the technology. The objectives of this study were to analyse socioeconomic status of referrals and to compare socioeconomic classes of referrals which were (a) accepted for testing and (b) proceeding to permanent implantation. Methods and results: All patients referred to the service from April 2010–February 2013 were included in this study. Using the Scottish Index of Multiple Deprivation 2012, each patient’s postcode was matched to the corresponding datazone quintile (1–5, in descending order of deprivation). Altogether 178 referrals were analysed with no significant differences between each quintile observed: of these 56.7% progressed to testing, and 36.5 % progressed to permanent implantation with no significant difference in proportion between each quintile. Conclusion: Reassuringly, patient selection for sacral nerve stimulation in our study demonstrated no significant discrimination by socioeconomic status.