COL11A1 is associated with developmental dysplasia of the hip and secondary osteoarthritis in the HUNT study.

Objective: Developmental dysplasia of the hip (DDH) is a congenital condition affecting 2-3% of all infants. DDH increases the risk of osteoarthritis, is the cause of 30 â€‹% of all total hip arthroplasties (THAs) in adults <40 years of age and can result in loss of life quality. Our aim was to explore the genetic background of DDH in order to improve diagnosis, management and longterm outcome. Design: We used the large, ongoing, longitudinal Trøndelag Health Study (HUNT) database. Case definition was based on ICD-9/-10 diagnoses of DDH, or osteoarthritis secondary to DDH. Analyses were performed using SAIGE software, with covariates including sex, batch, birth year and principal components. We included only single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥ 0.01, R2≥ 0.8 and Hardy-Weinberg equilibrium (HWE) P-value ≥ 0.0001. Significance level was set at p â€‹< â€‹5 â€‹× â€‹10-8. Meta-analysis using data from DDH and primary osteoarthritis genome-wide association studies (GWASs) was done using METAL software. The study was approved by the regional ethical committee. Results: Analysis included 69,500 individuals, of which 408 cases, and 8,531,386 SNPs. Two SNPs near COL11A1 were significantly associated with DDH; rs713162 (ߠ​= â€‹-0.43, SE â€‹= â€‹0.07, p â€‹= â€‹8.4 â€‹× â€‹10-9) and rs6577334 (ߠ​= â€‹-0.43, SE â€‹= â€‹0.08, p â€‹= â€‹8.9 â€‹× â€‹10-9). COL11A1 has previously been associated with acetabular dysplasia and osteoarthritis. Meta-analysis supported previous GWAS findings of both DDH and primary osteoarthritis. Conclusions: This large, genome-wide case-control study indicates an association between COL11A1 and DDH and is an important contribution to investigating the etiology of DDH, with further research needed.

The unintended consequences of artificial intelligence in paediatric radiology.

Over the past decade, there has been a dramatic rise in the interest relating to the application of artificial intelligence (AI) in radiology. Originally only 'narrow' AI tasks were possible; however, with increasing availability of data, teamed with ease of access to powerful computer processing capabilities, we are becoming more able to generate complex and nuanced prediction models and elaborate solutions for healthcare. Nevertheless, these AI models are not without their failings, and sometimes the intended use for these solutions may not lead to predictable impacts for patients, society or those working within the healthcare profession. In this article, we provide an overview of the latest opinions regarding AI ethics, bias, limitations, challenges and considerations that we should all contemplate in this exciting and expanding field, with a special attention to how this applies to the unique aspects of a paediatric population. By embracing AI technology and fostering a multidisciplinary approach, it is hoped that we can harness the power AI brings whilst minimising harm and ensuring a beneficial impact on radiology practice.

[Hip dysplasia in infants ­ screening, treatment and follow-up]. / Hofteleddsdysplasi hos spedbarn ­ screening, behandling og oppfølging.

BACKGROUND: Hip dysplasia occurs in up to 3 % of neonates and if untreated can lead to dislocated hip, osteoarthritis and the need for a hip prosthesis. The study aimed to identify routines for ultrasound screening, treatment and follow-up of hip dysplasia in Norwegian hospitals. MATERIAL AND METHOD: An online questionnaire was sent to radiologists responsible for paediatric examinations at all hospitals with paediatric departments. INTERPRETATION: Routines for screening, treatment and follow-up of hip dysplasia varied to a considerable degree between the hospitals.

European Society of Paediatric Radiology Artificial Intelligence taskforce: a new taskforce for the digital age.

A new task force dedicated to artificial intelligence (AI) with respect to paediatric radiology was created in 2021 at the International Paediatric Radiology (IPR) meeting in Rome, Italy (a joint society meeting by the European Society of Pediatric Radiology [ESPR] and the Society for Pediatric Radiology [SPR]). The concept of a separate task force dedicated to AI was borne from an ESPR-led international survey of health care professionals' opinions, expectations and concerns regarding AI integration within children's imaging departments. In this survey, the majority (> 80%) of ESPR respondents supported the creation of a task force and helped define our key objectives. These include providing educational content about AI relevant for paediatric radiologists, brainstorming ideas for future projects and collaborating on AI-related studies with respect to collating data sets, de-identifying images and engaging in multi-case, multi-reader studies. This manuscript outlines the starting point of the ESPR AI task force and where we wish to go.

Selective ultrasound screening for developmental hip dysplasia: effect on management and late detected cases. A prospective survey during 1991-2006.

BACKGROUND: Early treatment is considered essential for developmental dysplasia of the hip (DDH), but the choice of screening strategy is debated. OBJECTIVE: We evaluated the effect of a selective ultrasound (US) screening programme. MATERIALS AND METHODS: All infants born in a defined region during 1991-2006 with increased risk of developmental dysplasia of the hip, i.e. clinical hip instability, breech presentation, congenital foot deformities or a family history of DDH, underwent US screening at age 1-3 days. Severe sonographic dysplasia and dislocatable/dislocated hips were treated with abduction splints. Mild dysplasia and pathological instability, i.e. not dislocatable/dislocated hips were followed clinically and sonographically until spontaneous resolution, or until treatment became necessary. The minimum observation period was 5.5 years. RESULTS: Of 81,564 newborns, 11,539 (14.1%) were identified as at-risk, of whom 11,190 (58% girls) were included for further analyses. Of the 81,564 infants, 2,433 (3.0%) received early treatment; 1,882 (2.3%) from birth and 551 (0.7%) after 6 weeks or more of clinical and sonographic surveillance. An additional 2,700 (3.3%) normalised spontaneously after watchful waiting from birth. Twenty-six infants (0.32 per 1,000, 92% girls, two from the risk group) presented with late subluxated/dislocated hips (after 1 month of age). An additional 126 (1.5 per 1,000, 83% girls, one from the risk group) were treated after isolated late residual dysplasia. Thirty-one children (0.38 per 1,000) had surgical treatment before age 5 years. Avascular necrosis was diagnosed in seven of all children treated (0.27%), four after early and three after late treatment. CONCLUSION: The first 16 years of a standardised selective US screening programme for developmental dysplasia of the hip resulted in acceptable rates of early treatment and US follow-ups and low rates of late subluxated/dislocated hips compared to similar studies.

Radiographic measurements of hip dysplasia at skeletal maturity--new reference intervals based on 2,038 19-year-old Norwegians.

OBJECTIVE: Normative references for radiographic measurements commonly used in the diagnosis of developmental dysplasia of the hip at skeletal maturity are incomplete. The present study therefore aimed to establish new gender-specific standards for measurements reflecting the acetabular morphology, namely Sharp's angle, the acetabular roof angle of Tönnis (AA) and the acetabular depth-width ratio (ADR), and measurements reflecting the position of the femoral head related to the acetabulum, namely the center-edge (CE) angle of Wiberg, the refined CE angle of Ogata, and the femoral head extrusion index (FHEI). The joint space width (JSW) is also reported. MATERIALS AND METHODS: The population-based 1989 Bergen Birth Cohort (n = 3,935) was invited at age 19 years to a follow-up during 2007-09, of which 2,038 (52 %) attended. A standardized antero-posterior radiograph was assessed. The normative references are presented as mean ± standard deviation (SD) and 2.5-97.5 percentiles with 95 % confidence intervals. RESULTS: A total of 2,011 (841 males, 1,170 females, mean age 18.6 (SD 0.6)) radiographs were analyzed. Sharp's angle was 38.8° ± 3.5° in males and 40.7° ± 3.5° in females, with 97.5 percentiles of 46° and 47°, respectively. The CE angle was 32.1° ± 6.1° in males and 31.0° ± 6.1° in females, with 2.5 percentiles of 21° and 20°, respectively. The FHEI was 86.0 % ± 6.3 % in males and 85.6 % ± 6.6 % in females, with 2.5 percentiles of 74° and 73°, respectively. CONCLUSIONS: Updated gender-specific reference ranges for radiographic measurements commonly used for hip dysplasia at skeletal maturity are reported, similar to or slightly wider than those described in the literature. Statistically significant gender differences have been confirmed for most of the measurements.

Radiological findings for hip dysplasia at skeletal maturity. Validation of digital and manual measurement techniques.

OBJECTIVE: To report on intra-observer, inter-observer, and inter-method reliability and agreement for radiological measurements used in the diagnosis of hip dysplasia at skeletal maturity, as obtained by a manual and a digital measurement technique. MATERIALS AND METHODS: Pelvic radiographs from 95 participants (56 females) in a follow-up hip study of 18- to 19-year-old patients were included. Eleven radiological measurements relevant for hip dysplasia (Sharp's, Wiberg's, and Ogata's angles; acetabular roof angle of Tönnis; articulo-trochanteric distance; acetabular depth-width ratio; femoral head extrusion index; maximum teardrop width; and the joint space width in three different locations) were validated. Three observers measured the radiographs using both a digital measurement program and manually in AgfaWeb1000. Inter-method and inter- and intra-observer agreement were analyzed using the mean differences between the readings/readers, establishing the 95% limits of agreement. We also calculated the minimum detectable change and the intra-class correlation coefficient. RESULTS: Large variations among different radiological measurements were demonstrated. However, the variation was not related to the use of either the manual or digital measurement technique. For measurements with greater absolute values (Sharp's angle, femoral head extrusion index, and acetabular depth-width ratio) the inter- and intra-observer and inter-method agreements were better as compared to measurements with lower absolute values (acetabular roof angle, teardrop and joint space width). CONCLUSION: The inter- and intra-observer variation differs notably across different radiological measurements relevant for hip dysplasia at skeletal maturity, a fact that should be taken into account in clinical practice. The agreement between the manual and digital methods is good.

Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies.

BACKGROUND: To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative) for pancreatic autoantibodies [islet cell autoantibodies(ICA), glutamic acid decarboxylase antibodies (GADA) and insulinoma-associated antigen-2 antibodies (IA-2A)]. Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes. MATERIALS AND METHODS: In 261 newly diagnosed children with type 1 diabetes, we measured residual ß-cell function, ICA, GADA, and IA-2A at 1, 6 and 12 months after diagnosis. The genes KCNJ11, ABCC8, HNF1A, HNF4A and INS were sequenced in subjects AAB negative at diagnosis. We expressed recombinant K-ATP channels in Xenopus oocytes to analyse the functional effects of an ABCC8 mutation. RESULTS: Twenty-four patients (9.1%) tested AAB negative after one month. Patients, who were AAB-negative throughout the 12-month period, had higher residual ß-cell function (P = 0.002), lower blood glucose (P = 0.004), received less insulin (P = 0.05) and had lower HbA1c (P = 0.02) 12 months after diagnosis. One patient had a heterozygous mutation leading to the substitution of arginine at residue 1530 of SUR1 (ABCC8) by cysteine. Functional analyses of recombinant K-ATP channels showed that R1530C markedly reduced the sensitivity of the K-ATP channel to inhibition by MgATP. Morover, the channel was highly sensitive to sulphonylureas. However, there was no effect of sulfonylurea treatment after four weeks on 1.0-1.2 mg/kg/24 h glibenclamide. CONCLUSION: GAD, IA-2A, and ICA negative children with new onset type 1 diabetes have slower disease progression as assessed by residual beta-cell function and improved glycemic control 12 months after diagnosis. One out of 24 had a mutation in ABCC8, suggesting that screening of ABCC8 should be considered in patients with AAB negative type 1 diabetes.

DNA hypomethylation, transient neonatal diabetes, and prune belly sequence in one of two identical twins.

One known genetic mechanism for transient neonatal diabetes is loss of methylation at 6q24. The etiology of prune belly sequence is unknown but a genetic defect, affecting the mesoderm from which the triad abdominal muscle hypoplasia, urinary tract abnormalities, and cryptorchidism develop, has been suggested. We investigated a family, including one twin, with transient neonatal diabetes and prune belly sequence. Autoantibody tests excluded type 1 diabetes. Microsatellite marker analysis confirmed the twins being monozygotic. We identified no mutations in ZFP57, KCNJ11, ABCC8, GCK, HNF1A, HNF1B, HNF3B, IPF1, PAX4, or ZIC3. The proband had loss of methylation at the 6q24 locus TNDM and also at the loci IGF2R, DIRAS3, and PEG1, while the other family members, including the healthy monozygotic twin, had normal findings. The loss of methylation on chromosome 6q24 and elsewhere may indicate a generalized maternal hypomethylation syndrome, which accounts for both transient neonatal diabetes and prune belly sequence.