Reticulon 2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity.

Heterozygous RTN2 variants have been previously identified in a limited cohort of families affected by autosomal dominant spastic paraplegia (SPG12-OMIM:604805) with a variable age of onset. Nevertheless, the definitive validity of SPG12 remains to be confidently confirmed due to scarcity of supporting evidence. In our study, we identified and validated seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) using exome, genome and Sanger sequencing coupled with deep-phenotyping. All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography. Despite a slowly progressive disease course, all patients remained ambulatory over a mean disease duration of 19.71 ± 13.70 years. Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain. Treatment of the mutant with an endoplasmic/sarcoplasmic reticulum Ca2+ reuptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences, suggesting a potential therapeutic benefit for RTN2-disorder. Despite Reticulon-2 being an endoplasmic reticulum (ER)-resident membrane shaping protein, our analysis of patient fibroblast cells did not find significant alterations in ER structure or the response to ER stress. Our findings delineate a distinct form of autosomal recessive dHMN with pyramidal features associated with Reticulon-2 deficiency. This phenotype shares similarities with SIGMAR1-related dHMN, and Silver-like syndromes, providing valuable insights into the clinical spectrum and potential therapeutic strategies for RTN2-related dHMN.

Conclusion of diagnostic odysseys due to inversions disrupting GLI3 and FBN1.

Many genetic testing methodologies are biased towards picking up structural variants (SVs) that alter copy number. Copy-neutral rearrangements such as inversions are therefore likely to suffer from underascertainment. In this study, manual review prompted by a virtual multidisciplinary team meeting and subsequent bioinformatic prioritisation of data from the 100K Genomes Project was performed across 43 genes linked to well-characterised skeletal disorders. Ten individuals from three independent families were found to harbour diagnostic inversions. In two families, inverted segments of 1.2/14.8 Mb unequivocally disrupted GLI3 and segregated with skeletal features consistent with Greig cephalopolysyndactyly syndrome. For one family, phenotypic blending was due to the opposing breakpoint lying ~45 kb from HOXA13 In the third family, long suspected to have Marfan syndrome, a 2.0 Mb inversion disrupting FBN1 was identified. These findings resolved lengthy diagnostic odysseys of 9-20 years and highlight the importance of direct interaction between clinicians and data-analysts. These exemplars of a rare mutational class inform future SV prioritisation strategies within the NHS Genomic Medicine Service and similar genome sequencing initiatives. In over 30 years since these two disease-gene associations were identified, large inversions have yet to be described and so our results extend the mutational spectra linked to these conditions.

Use of genome sequencing to hunt for cryptic second-hit variants: analysis of 31 cases recruited to the 100 000 Genomes Project.

BACKGROUND: Current clinical testing methods used to uncover the genetic basis of rare disease have inherent limitations, which can lead to causative pathogenic variants being missed. Within the rare disease arm of the 100 000 Genomes Project (100kGP), families were recruited under the clinical indication 'single autosomal recessive mutation in rare disease'. These participants presented with strong clinical suspicion for a specific autosomal recessive disorder, but only one suspected pathogenic variant had been identified through standard-of-care testing. Whole genome sequencing (WGS) aimed to identify cryptic 'second-hit' variants. METHODS: To investigate the 31 families with available data that remained unsolved following formal review within the 100kGP, SVRare was used to aggregate structural variants present in <1% of 100kGP participants. Small variants were assessed using population allele frequency data and SpliceAI. Literature searches and publicly available online tools were used for further annotation of pathogenicity. RESULTS: Using these strategies, 8/31 cases were solved, increasing the overall diagnostic yield of this cohort from 10/41 (24.4%) to 18/41 (43.9%). Exemplar cases include a patient with cystic fibrosis harbouring a novel exonic LINE1 insertion in CFTR and a patient with generalised arterial calcification of infancy with complex interlinked duplications involving exons 2-6 of ENPP1. Although ambiguous by short-read WGS, the ENPP1 variant structure was resolved using optical genome mapping and RNA analysis. CONCLUSION: Systematic examination of cryptic variants across a multi-disease cohort successfully identifies additional pathogenic variants. WGS data analysis in autosomal recessive rare disease should consider complex structural and small intronic variants as potentially pathogenic second hits.

Disparities in paediatric radiology research publications from low- and lower middle-income countries: a time for change.

The positive impact of diversity on health research and outcomes is well-recognised and widely published. Despite this, published evidence shows that at every step of the research pathway, issues of equity, diversity and inclusion (EDI) arise. There is evidence of a lack of diversity within research teams, in the research questions asked/research participants recruited, on grant review/funding panels, amongst funded researchers and on the editorial boards and reviewer pools of the journals to which results are submitted for peer-reviewed publication. Considering the journal Pediatric Radiology, while its editorial board of 92 members has at least one member affiliated to a country in every region of the world, the majority are in North America (n=52, 57%) and Europe (n=30, 33%) and only two (2%) are affiliated to institutions in a lower middle-income country (LMIC) (India, Nigeria), with one (1%) affiliated to an institution in an upper middle-income country (UMIC) (Peru) and none in a low-income country (LIC). Pediatric Radiology is "…the official journal of the European Society of Paediatric Radiology, the Society for Pediatric Radiology, the Asian and Oceanic Society for Pediatric Radiology and the Latin American Society of Pediatric Radiology". However, of the total number of manuscripts submitted for potential publication in the four years 2019 through 2022, only 0.03% were from a LIC and only 7.9% were from a LMIC. Further, the frequency of acceptance of manuscripts from UMIC was seven times higher than that from LMIC (no manuscripts were published from LIC). Increased collaboration is required between researchers across the globe to better understand the barriers to equity in the funding, conduct and publication of research from LIC and LMIC and to identify ways in which we can overcome them together.

The prevalence and phenotypic range associated with biallelic PKDCC variants.

PKDCC encodes a component of Hedgehog signalling required for normal chondrogenesis and skeletal development. Although biallelic PKDCC variants have been implicated in rhizomelic shortening of limbs with variable dysmorphic features, this association was based on just two patients. In this study, data from the 100 000 Genomes Project was used in conjunction with exome sequencing and panel-testing results accessed via international collaboration to assemble a cohort of eight individuals from seven independent families with biallelic PKDCC variants. The allelic series included six frameshifts, a previously described splice-donor site variant and a likely pathogenic missense variant observed in two families that was supported by in silico structural modelling. Database queries suggested that the prevalence of this condition is between 1 of 127 and 1 of 721 in clinical cohorts with skeletal dysplasia of unknown aetiology. Clinical assessments, combined with data from previously published cases, indicate a predominantly upper limb involvement. Micrognathia, hypertelorism and hearing loss appear to be commonly co-occurring features. In conclusion, this study strengthens the link between biallelic inactivation of PKDCC and rhizomelic limb-shortening and will enable clinical testing laboratories to better interpret variants in this gene.

Expanding the phenotype of SPARC-related osteogenesis imperfecta: clinical findings in two patients with pathogenic variants in SPARC and literature review.

BACKGROUND: Secreted protein, acidic, cysteine rich (SPARC)-related osteogenesis imperfecta (OI), also referred to as OI type XVII, was first described in 2015, since then there has been only one further report of this form of OI. SPARC is located on chromosome 5 between bands q31 and q33. The encoded protein is necessary for calcification of the collagen in bone, synthesis of extracellular matrix and the promotion of changes to cell shape. METHODS: We describe a further two patients with previously unreported homozygous SPARC variants with OI: one splice site; one nonsense pathogenic variant. We present detailed information on the clinical and radiological phenotype and correlate this with their genotype. There are only two previous reports by Mendozo-Londono et al and Hayat et al with clinical descriptions of patients with SPARC variants. RESULTS: From the data we have obtained, common clinical features in individuals with OI type XVII caused by SPARC variants include scoliosis (5/5), vertebral compression fractures (5/5), multiple long bone fractures (5/5) and delayed motor development (3/3). Interestingly, 2/4 patients also had abnormal brain MRI, including high subcortical white matter changes, abnormal fluid-attenuated inversion in the para-atrial white matter and a large spinal canal from T10 to L1. Of significance, both patients reported here presented with significant neuromuscular weakness prompting early workup. CONCLUSION: Common phenotypic expressions include delayed motor development with neuromuscular weakness, scoliosis and multiple fractures. The data presented here broaden the phenotypic spectrum establishing similar patterns of neuromuscular presentation with a presumed diagnosis of 'myopathy'.

Biallelic cGMP-dependent type II protein kinase gene (PRKG2) variants cause a novel acromesomelic dysplasia.

BACKGROUND: C-type natriuretic peptide (CNP), its endogenous receptor, natriuretic peptide receptor-B (NPR-B), as well as its downstream mediator, cyclic guanosine monophosphate (cGMP) dependent protein kinase II (cGKII), have been shown to play a pivotal role in chondrogenic differentiation and endochondral bone growth. In humans, biallelic variants in NPR2, encoding NPR-B, cause acromesomelic dysplasia, type Maroteaux, while heterozygous variants in NPR2 (natriuretic peptide receptor 2) and NPPC (natriuretic peptide precursor C), encoding CNP, cause milder phenotypes. In contrast, no variants in cGKII, encoded by the protein kinase cGMP-dependent type II gene (PRKG2), have been reported in humans to date, although its role in longitudinal growth has been clearly demonstrated in several animal models. METHODS: Exome sequencing was performed in two girls with severe short stature due to acromesomelic limb shortening, brachydactyly, mild to moderate platyspondyly and progressively increasing metaphyseal alterations of the long bones. Functional characterisation was undertaken for the identified variants. RESULTS: Two homozygous PRKG2 variants, a nonsense and a frameshift, were identified. The mutant transcripts are exposed to nonsense-mediated decay and the truncated mutant cGKII proteins, partially or completely lacking the kinase domain, alter the downstream mitogen activation protein kinase signalling pathway by failing to phosphorylate c-Raf 1 at Ser43 and subsequently reduce ERK1/2 activation in response to fibroblast growth factor 2. They also downregulate COL10A1 and upregulate COL2A1 expression through SOX9. CONCLUSION: In conclusion, we have clinically and molecularly characterised a new acromesomelic dysplasia, acromesomelic dysplasia, PRKG2 type (AMDP).

Professional practice and awareness of child abuse among radiologists and radiologic technologists: results from Saudi Arabia.

BACKGROUND: The knowledge, awareness and professionalism of health care providers in the field of child protection are crucial in identifying and reporting suspected child abuse. Radiologic technologists and radiologists play a vital role in the diagnosis of suspected physical child abuse. OBJECTIVE: To assess current practice, knowledge and awareness of child abuse among radiologic technologists and radiologists in Saudi Arabia. MATERIALS AND METHODS: We distributed an internet-based questionnaire to radiologic technologists and radiologists working in Saudi Arabia via national radiology societies and social media channels over a 6-week period (27 October to 8 December 2021). Survey questions covered knowledge regarding child abuse, professional practice in radiology departments in Saudi Arabia in cases of suspected physical abuse (SPA), and knowledge of the national legislation and reporting and acting procedures in child abuse. RESULTS: A total of 315 respondents (224 radiologic technologists and 91 radiologists) participated in this study. The median score for knowledge of abuse was higher amongst radiologists (4.8) than radiologic technologists (4.0); P < 0.001. In total, 210 (93.8%) radiologic technologists and 61 (67.0%) radiologists reported that there was no protocol (i.e. skeletal survey) at their hospital for imaging children with SPA. Most radiologic technologists had no training in paediatric radiology (165/224, 73.7%) and most radiologists had received no training in evaluating imaging performed for SPA (73/91, 80.2%). More than half of respondents - 131 (58.5%) radiologic technologists and 44 (48.4%) radiologists - were not familiar with the reporting and acting procedures at their hospitals in cases of child abuse. CONCLUSION: Although radiologic technologists and radiologists in Saudi Arabia have good knowledge and awareness of child abuse in general, they lack specific knowledge of the reporting and acting procedures at their hospitals in cases of suspected child abuse. National imaging guidelines and training courses are needed to develop appropriate skills in the recognition, imaging and reporting of SPA in infants and young children in Saudi Arabia.

The effect of selective ultrasound screening on the incidence of late presentation of developmental hip dysplasia-a meta-analysis.

Different screening strategies for developmental dysplasia of the hip (DDH) exist. Despite screening efforts, cases of late presentation continue to occur, often necessitating surgery. This systematic review and meta-analysis assess the effect of newborn selective ultrasound screening for DDH on the incidence of late presentation in infants and children, compared to a universal ultrasound strategy. A systematic search across Medline and EMBASE databases was performed between January 1950 and February 2021. A consensus-based evaluation of abstracts led to retrieval of relevant full text, original articles or systematic reviews in English only. These were assessed according to agreed eligibility criteria, and their reference lists were reviewed to identify additional eligible publications. Following final consensus on included publications, data was extracted, analysed and reported as per PRISMA and Prospero (CRD42021241957) guidelines. The 16 eligible studies consisted of 2 randomised controlled trials and 14 cohort studies, published between 1989 and 2014, with a total of 511,403 participants. In total, 121,470 (23.8%) received a neonatal hip ultrasound, of whom 58,086 and 63,384 were part of a selective or a universal ultrasound screening strategy, respectively. The difference in the proportion of late presentation between the universal and selective strategies was 0.0904 per 1,000 (P = 0.047). The time effect, i.e. the difference between early and late presentation defined respectively, as less than and more than 3 months of age, regardless of screening strategy, was not significant (P = 0.272). Although there was variability in study design and reporting, the quality of the evidence, based on the critical appraisal skills programme appraisal tools, was generally good. Compared to universal ultrasound screening for DDH, selective screening resulted in a slightly higher rate of late presentation. Uniformity in design and reporting of DDH studies and a cost-effectiveness analysis are needed.

Benign enlargement of the subarachnoid spaces and subdural collections-when to evaluate for abuse.

In infants without a history of trauma, subdural haemorrhages should raise the concern for an abusive head injury, particularly when they are associated with bridging vein clotting/rupture or with septations. However, non-haemorrhagic, fluid-appearing subdural collections (also called hygromas) may also be the result of abuse. Subdural collections have also been uncommonly observed in patients with benign enlargement of the subarachnoid spaces (BESS) and a few large-scale studies accurately investigate the incidence and the significance. Currently, there is a wide variation of practices in children with BESS and subdural collections. Due to the social risks associated with abuse evaluation and the perceived risk of radiation exposure, there might be a reluctance to fully evaluate these children in some centres. The diagnosis of physical abuse cannot be substantiated nor safely excluded in infants with BESS and subdural collection(s), without investigation for concomitant traumatic findings. The exact prevalence of occult injuries and abuse in these infants is unknown. In macrocephalic infants with subdural collections and imaging features of BESS, thorough investigations for abuse are warranted and paediatricians should consider performing full skeletal surveys even when fundoscopy, social work consult, and detailed clinical evaluation are unremarkable.

Controversial aspects of imaging in child abuse: a second roundtable discussion from the ESPR child abuse taskforce.

This second roundtable discussion was convened at the 56th European Society of Paediatric Radiology (ESPR) 2022 Annual Meeting in Marseille, France, to discuss controversial aspects of imaging in child abuse. The following topics were discussed: Fracture dating-the published literature is broadly similar with respect to the identification of the radiographic stages of bony healing. The non-expert/general radiologist is encouraged to use broad descriptors of fracture healing (acute, healing or old) within their reports, rather than attempting to date fractures. The more experienced/expert radiologist, who may provide a timeframe/range to assist the courts, should be aware that any published timeframes are not absolute and that recent research indicates that the rate of healing may differ according to the bone affected and the age of the patient. Whole spine imaging in suspected abusive head trauma-this is recommended to enable a complete assessment of the neuraxis when abusive head trauma is suspected or diagnosed, particularly in the presence of intracranial and cervical subdural haemorrhage and cervical ligamentous injury. Cranial imaging in suspected physical abuse-both computed tomography (CT) and magnetic resonance imaging (MRI) remain complimentary depending on the clinical context in which they are used with CT remaining first-line in the assessment of children with (suspected abusive) head trauma prior to an early MRI. MRI is superior in its assessment of parenchymal injury and may be employed as first-line in age appropriate asymptomatic siblings of a child with suspected physical abuse.

Current and emerging artificial intelligence applications for pediatric musculoskeletal radiology.

Artificial intelligence (AI) is playing an ever-increasing role in radiology (more so in the adult world than in pediatrics), to the extent that there are unfounded fears it will completely take over the role of the radiologist. In relation to musculoskeletal applications of AI in pediatric radiology, we are far from the time when AI will replace radiologists; even for the commonest application (bone age assessment), AI is more often employed in an AI-assist mode rather than an AI-replace or AI-extend mode. AI for bone age assessment has been in clinical use for more than a decade and is the area in which most research has been conducted. Most other potential indications in children (such as appendicular and vertebral fracture detection) remain largely in the research domain. This article reviews the areas in which AI is most prominent in relation to the pediatric musculoskeletal system, briefly summarizing the current literature and highlighting areas for future research. Pediatric radiologists are encouraged to participate as members of the research teams conducting pediatric radiology artificial intelligence research.

Autonomous artificial intelligence in pediatric radiology: the use and perception of BoneXpert for bone age assessment.

BACKGROUND: The autonomous artificial intelligence (AI) system for bone age rating (BoneXpert) was designed to be used in clinical radiology practice as an AI-replace tool, replacing the radiologist completely. OBJECTIVE: The aim of this study was to investigate how the tool is used in clinical practice. Are radiologists more inclined to use BoneXpert to assist rather than replace themselves, and how much time is saved? MATERIALS AND METHODS: We sent a survey consisting of eight multiple-choice questions to 282 radiologists in departments in Europe already using the software. RESULTS: The 97 (34%) respondents came from 18 countries. Their answers revealed that before installing the automated method, 83 (86%) of the respondents took more than 2 min per bone age rating; this fell to 20 (21%) respondents after installation. Only 17/97 (18%) respondents used BoneXpert to completely replace the radiologist; the rest used it to assist radiologists to varying degrees. For instance, 39/97 (40%) never overruled the automated reading, while 9/97 (9%) overruled more than 5% of the automated ratings. The majority 58/97 (60%) of respondents checked the radiographs themselves to exclude features of underlying disease. CONCLUSION: BoneXpert significantly reduces reporting times for bone age determination. However, radiographic analysis involves more than just determining bone age. It also involves identification of abnormalities, and for this reason, radiologists cannot be completely replaced. AI systems originally developed to replace the radiologist might be more suitable as AI assist tools, particularly if they have not been validated to work autonomously, including the ability to omit ratings when the image is outside the range of validity.

Postmortem computed tomography plus forensic autopsy for determining the cause of death in child fatalities.

BACKGROUND: Postmortem computed tomography (CT) and magnetic resonance imaging have been gradually introduced to forensic pathology centres over the past two decades, with varying results in comparison to autopsy. OBJECTIVE: The purpose of this study was to determine the accuracy of postmortem CT in determining a cause of death in children who died of unnatural causes. MATERIALS AND METHODS: This was a prospective recruitment of 30 children (< 18 years) who underwent postmortem CT and a forensic autopsy. A cause of death was independently assigned by two experienced paediatric radiologists and compared to that of the forensic autopsy. RESULTS: A correct cause of death was assigned by reviewers 1 and 2 in 70% (n = 21/30) and 67% (n = 20/30) of cases, respectively. For gunshot injuries and blunt force head injuries, there was 91% (n = 10/11) and 100% (n = 6/6) agreement between forensic autopsy and both reviewers, respectively. No cause of death could be assigned by reviewers 1 and 2 in 27% (n = 8) and 30% (n = 9) of cases, respectively. An incorrect cause of death was assigned by both reviewers in one case (3%). The Cohen Kappa level of agreement between the forensic autopsy and reviewers 1 and 2 was k = 0.624 (95% confidence interval [CI]: 0.45-0.80, P = 0) and k = 0.582 (95% CI 0.41-0.76, P = 0), respectively. There was near perfect agreement between reviewers 1 and 2 (k = 0.905) (95% CI 0.78-1.00, P = 0). CONCLUSION: Postmortem CT has good diagnostic accuracy for identifying a cause of death related to trauma, but it has poor accuracy for children dying from causes not associated with apparent physical injury.

The (extended) achondroplasia foramen magnum score has good observer reliability.

BACKGROUND: Achondroplasia is the most common skeletal dysplasia. A significant complication is foramen magnum stenosis. When severe, compression of the spinal cord may result in sleep apnea, sudden respiratory arrest and death. To avoid complications, surgical decompression of the craniocervical junction is offered in at-risk cases. However, practice varies among centres. To standardize magnetic resonance (MR) reporting, the achondroplasia foramen magnum score was recently developed. The reliability of the score has not been assessed. OBJECTIVE: To assess the interobserver reliability of the achondroplasia foramen magnum score. MATERIALS AND METHODS: Base of skull imaging of children with achondroplasia under the care of Sheffield Children's Hospital was retrospectively and independently reviewed by four observers using the achondroplasia foramen magnum score. Two-way random-effects intraclass coefficient (ICC) was used to assess inter- and intra-observer reliability. RESULTS: Forty-nine eligible cases and five controls were included. Of these, 10 were scored normal, 17 had a median score of 1 (mild narrowing), 11 had a median score of 2 (effacement of cerebral spinal fluid), 10 had a score of 3 (compression of cord) and 6 had a median score of 4 (cord myelopathic change). Interobserver ICC was 0.72 (95% confidence interval = 0.62-0.81). Intra-observer ICC ranged from 0.60 to 0.86. Reasons for reader disagreement included flow void artefact, subtle T2 cord signal and myelopathic T2 cord change disproportionate to canal narrowing. CONCLUSION: The achondroplasia foramen magnum score has good interobserver reliability. Imaging features leading to interobserver disagreement have been identified. Further research is required to prospectively validate the score against clinical outcomes.

A hypomorphic allele of SLC35D1 results in Schneckenbecken-like dysplasia.

We report the case of a consanguineous couple who lost four pregnancies associated with skeletal dysplasia. Radiological examination of one fetus was inconclusive. Parental exome sequencing showed that both parents were heterozygous for a novel missense variant, p.(Pro133Leu), in the SLC35D1 gene encoding a nucleotide sugar transporter. The affected fetus was homozygous for the variant. The radiological features were reviewed, and being similar, but atypical, the phenotype was classified as a 'Schneckenbecken-like dysplasia.' The effect of the missense change was assessed using protein modelling techniques and indicated alterations in the mouth of the solute channel. A detailed biochemical investigation of SLC35D1 transport function and that of the missense variant p.(Pro133Leu) revealed that SLC35D1 acts as a general UDP-sugar transporter and that the p.(Pro133Leu) mutation resulted in a significant decrease in transport activity. The reduced transport activity observed for p.(Pro133Leu) was contrasted with in vitro activity for SLC35D1 p.(Thr65Pro), the loss-of-function mutation was associated with Schneckenbecken dysplasia. The functional classification of SLC35D1 as a general nucleotide sugar transporter of the endoplasmic reticulum suggests an expanded role for this transporter beyond chondroitin sulfate biosynthesis to a variety of important glycosylation reactions occurring in the endoplasmic reticulum.

AIFM1-associated X-linked spondylometaphyseal dysplasia with cerebral hypomyelination.

Spondylometaphyseal dysplasia with cerebral hypomyelination (SMD-H) is a very rare but distinctive phenotype, unusually combining spondylometaphyseal dysplasia with hypomyelinating leukodystrophy. Recently, SMD-H has been associated with variants confined to a specific intra-genic locus involving Exon 7, suggesting that AIFM1 plays an important role in bone development and metabolism as well as cerebral myelination. Here we describe two further affected boys, one with a novel intronic variant associated with skipping of Exon 7 of AIFM1 and the other a synonymous variant within Exon 7 of AIFM1. We describe their clinical course and radiological and genetic findings, providing further insight into the natural history of this condition.

The diagnostic performance of chest computed tomography in the detection of rib fractures in children investigated for suspected physical abuse: a systematic review and meta-analysis.

OBJECTIVES: To assess the diagnostic performance of chest CT in the detection of rib fractures in children investigated for suspected physical abuse (SPA). METHODS: Medline, Web of Science and Cochrane databases were searched from January 1980 to April 2020. The QUADAS-2 tool was used to assess the quality of the eligible English-only studies following which a formal narrative synthesis was constructed. Studies reporting true-positive, false-positive, true-negative, and false-negative results were included in the meta-analysis. Overall sensitivity and specificity of chest CT for rib fracture detection were calculated, irrespective of fracture location, and were pooled using a univariate random-effects meta-analysis. The diagnostic accuracy of specific locations along the rib arc (anterior, lateral or posterior) was assessed separately. RESULTS: Of 242 identified studies, 4 met the inclusion criteria. Of these, 2 were included in the meta-analysis. Chest CT identified 142 rib fractures compared to 79 detected by initial skeletal survey chest radiographs in live children with SPA. Post-mortem CT (PMCT) has low sensitivity (34%) but high specificity (99%) in the detection of rib fractures when compared to the autopsy reference standard. PMCT has low sensitivity (45%, 21% and 42%) but high specificity (99%, 97% and 99%) at anterior, lateral and posterior rib locations, respectively. CONCLUSIONS: Chest CT detects more rib fractures than initial skeletal survey chest radiographs in live children with SPA. PMCT has low sensitivity but high specificity for detecting rib fractures in children investigated for SPA. KEY POINTS: • PMCT has low sensitivity (34%) but high specificity (99%) in the detection of rib fractures; extrapolation to CT in live children is difficult. • No studies have compared chest CT with the current accepted practice of initial and follow-up skeletal survey chest radiographs in the detection of rib fractures in live children investigated for SPA.

Comparison of prevalence and characteristics of fractures in term and preterm infants in the first 3 years of life.

BACKGROUND: Preterm infants may be more vulnerable to fractures due to various factors, including metabolic bone disease, but an increased risk of fractures up to the age of 2 is unproven. OBJECTIVE: To compare fracture patterns in premature and full-term children in the first 3 years of life. MATERIALS AND METHODS: A retrospective study was conducted. We excluded any child who returned with the same injury, with known metabolic bone disease, with any disease or condition known to reduce bone density, who received any medication known to affect Vitamin D metabolism within 3 months of enrollment or who had fractures post-surgery/resuscitation. Variables such as the number of fractures sustained each year, age of presentation to the Emergency Department and mechanism of injury were compared between the preterm and term groups using statistical analysis (χ2 and Fisher exact test for categorical variables and Student's t-test for continuous variables). Simple linear regression was performed on the total number of fractures sustained by age 3. RESULTS: Forty-four children with fractures were included. Of these, none were born extremely preterm, 24 (55%) were preterm, and 20 (45%) were born at term. Mean gestational ages of the preterm and term groups were 32 weeks 3 days and 39 weeks 6 days, respectively. There were no extremely low birth weight or very low birth weight children. There was no significant difference in the number of fractures sustained yearly, the age of presentation to the Emergency Department or the site of fracture between preterm and term groups. Linear regression showed that the total number of fractures sustained by age 3 years was unrelated to prematurity status, gender or birth weight category. CONCLUSION: No significant difference in fracture number or pattern was identified.

Validating scoring systems for fracture healing in infants and young children: pilot study.

BACKGROUND: Recent studies have analysed birth-related clavicular fractures to propose time frames for healing that could be applied to dating of all fractures in cases of suspected child abuse. OBJECTIVE: To assess differences in healing rates between femoral fractures and birth-related clavicular fractures in infants and young children. MATERIALS AND METHODS: A retrospective 5-year pilot study of femoral fractures in children younger than 3 years of age was performed. Anonymised radiographs were independently scored by two radiologists for stages of fracture healing. In cases of reader disagreement, radiographs were independently scored by a third radiologist. RESULTS: In total, 74 radiographs (30 children) met the inclusion criteria. Fracture healing evolved over time with subperiosteal new bone formation (SPNBF) appearing first, followed by callus then remodelling. A power calculation for a single proportion, with a level of confidence of 95% and a margin of error of 5%, showed that in a definitive study, 359 radiographs would be required. CONCLUSION: Although the overall pattern of healing is similar, in this small pilot study, the earliest times for SPNBF and callus formation in femoral fractures appeared to lag behind healing of birth-related clavicular fractures. Remodelling appeared earlier than remodelling of clavicular fractures. A power calculation has determined numbers of femoral radiographs (359) required for a definitive study.