How Much Does Paediatric Femoral Lengthening Cost? A Cost Comparison between Magnetic Lengthening Nails and External Fixators.

Aim: Motorised intramedullary lengthening nails are considered more expensive than external fixators for limb lengthening. This research aims to compare the cost of femoral lengthening in children using the PRECICE magnetic lengthening nail with external fixation. Methods: Retrospective analysis of 50 children who underwent femoral lengthening. One group included patients who were treated with PRECICE lengthening nails, the other group included patients who had lengthening with external fixation. Each group included 25 patients aged between 11 and 17 years. The patients in both groups were matched for age. Cost analysis was performed following micro-costing and analysis of the used resources during the different phases of the treatments. Results: Each group's mean patient age was 14.7 years. Lengthening nails were associated with longer operative times compared with external fixators, both for implantation and removal surgery (p-values of 0.007 and < 0.0001, respectively). Length of stay following the implantation surgery, frequency of radiographs and frequency of outpatient department appointments were all lower with lengthening nails. The overall cost of lengthening nails was £1393 more than external fixators, however, this difference was not statistically significant (p-value = 0.088). Conclusion: The difference in the mean costs between femoral lengthening with lengthening nails versus external fixators was not statistically significant. Further research to review the effectiveness of the devices and the quality of life during the lengthening process is crucial for robust health economic evaluation. How to cite this article: Hafez M, Nicolaou N, Offiah A, et al. How Much Does Paediatric Femoral Lengthening Cost? A Cost Comparison between Magnetic Lengthening Nails and External Fixators. Strategies Trauma Limb Reconstr 2023;18(1):16-20.

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.

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.

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.

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.

Neonatal osteofibrous dysplasia: Synchronous tibial and fibular involvement is common.

Osteofibrous dysplasia is a rare non-malignant fibro-osseous bone tumour, first described and characterised under this name by Campanacci in 1976. It is most commonly encountered in the tibia of children and young adults, but less frequently seen in the neonate with only few prior reports in the literature. We report a case of neonatal congenital osteofibrous dysplasia, presenting with unilateral limb deformity at birth. Radiographs demonstrated well-defined mixed lytic-sclerotic lesions, in a previously unreported distribution in this age-group, confined to the distal metadiaphysis of the affected tibia and fibula. Open surgery was performed for deformity correction, with tissue biopsy confirming the radiographically-suspected diagnosis. We present the up-to-date clinical, radiological and pathological findings in this case of a rare pathology with some novel features, within this age group, in disease distribution and consequent radiographic appearances. OFD should be considered in the differential of similar congenital deforming bone lesions of the lower limb. We also review the small number of previously published cases of congenital OFD in the neonate, noting in particular that the frequency of ipsilateral fibular involvement appears to be higher than that observed in older patients.

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.

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).

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'.

International Consensus Statement on the diagnosis, multidisciplinary management and lifelong care of individuals with achondroplasia.

Achondroplasia, the most common skeletal dysplasia, is characterized by a variety of medical, functional and psychosocial challenges across the lifespan. The condition is caused by a common, recurring, gain-of-function mutation in FGFR3, the gene that encodes fibroblast growth factor receptor 3. This mutation leads to impaired endochondral ossification of the human skeleton. The clinical and radiographic hallmarks of achondroplasia make accurate diagnosis possible in most patients. However, marked variability exists in the clinical care pathways and protocols practised by clinicians who manage children and adults with this condition. A group of 55 international experts from 16 countries and 5 continents have developed consensus statements and recommendations that aim to capture the key challenges and optimal management of achondroplasia across each major life stage and sub-specialty area, using a modified Delphi process. The primary purpose of this first International Consensus Statement is to facilitate the improvement and standardization of care for children and adults with achondroplasia worldwide in order to optimize their clinical outcomes and quality of life.

Femoral Lengthening in Children-A Comparison Between Magnetic Intramedullary Lengthening Nails and External Fixators.

BACKGROUND: Femoral lengthening can be achieved using external fixators or intramedullary lengthening nails. The purpose of this research was to compare the outcome of femoral lengthening in children using PRECICE magnetic lengthening nails with lengthening external fixators. METHODS: Retrospective analysis of 50 children who had femoral lengthening. Group A included patients who had lengthening with external fixation, patients in Group B had lengthening with PRECICE intramedullary lengthening nails. Each group included 25 patients. The sample strictly included children aged between 11 and 17 years. Patients in each group were matched according to age and indication for lengthening whether congenital or acquired conditions. The outcomes focused on the ability to achieve target length, healing index, residual malalignment, length of hospitalization following the osteotomy surgery, and encountered complications. RESULTS: Mean patient age was 14.7 years for each group. The length gain was 42±12 mm for Group A and 41.6±8 mm for Group B (P=0.84). Lengthening nails achieved the target length more accurately compared with external fixation (P=0.017). The healing index was significantly higher in group A with 53.2±19 days/cm compared with 40.2±14 days/cm in group B (P=0.03). Group A had significantly higher complications than group B (P<0.0001). There was no statistically significant difference in the final coronal malalignment between the 2 groups (P=0.2). The mean length of stay was 9.2±5.8 days for group A and 4.2±3.3 days for group B (P=0.0005). CONCLUSION: Magnetic lengthening nails are clinically effective for femoral lengthening in the pediatric population. Compared with external fixation, healing index and complications were more favorable with PRECICE nails. Further research is required to study the cost-effectiveness of this technique. LEVEL OF EVIDENCE: Level IV-case series.

A mild case of acromesomelic dysplasia, type Maroteaux with novel natriuretic peptide receptor B (NPR2) variants.

Acromesomelic dysplasia, type Maroteaux is caused by variants in NPR2. It is a severe chondrodysplasia resulting in shortening of the middle and distal segments of the limbs. Limb length at birth may be normal but decreased growth becomes obvious in the first 2 years of life. Here we present an 11-year-old male with mild but typical skeletal features of acromesomelic dysplasia, type Maroteaux. Whole exome sequencing has identified two likely pathogenic variants in NPR2 which have not previously been reported in individuals with acromesomelic dysplasia, type Maroteaux. Given these findings, a diagnosis of AMDM should be considered in individuals with characteristic radiological findings, even if stature is only modestly affected.

Diagnostic yield of rare skeletal dysplasia conditions in the radiogenomics era.

BACKGROUND: Skeletal dysplasia (SD) conditions are rare genetic diseases of the skeleton, encompassing a heterogeneous group of over 400 disorders, and represent approximately 5% of all congenital anomalies. Developments in genetic and treatment technologies are leading to unparalleled therapeutic advances; thus, it is more important than ever to molecularly confirm SD conditions. Data on 'rates-of-molecular yields' in SD conditions, through exome sequencing approaches, is limited. Figures of 39% and 52.5% have been reported in the USA (n = 54) and South Korea (n = 185) respectively. METHODS: We discuss a single-centre (in the UK) experience of whole-exome sequencing (WES) in a cohort of 15 paediatric patients (aged 5 months to 12 years) with SD disorders previously molecularly unconfirmed. Our cohort included patients with known clinical diagnoses and undiagnosed skeletal syndromes. Extensive phenotyping and expert radiological review by a panel of international SD radiology experts, coupled with a complex bioinformatics pipeline, allowed for both gene-targeted and gene-agnostic approaches. RESULTS: Significant variants leading to a likely or confirmed diagnosis were identified in 53.3% (n = 8/15) of patients; 46.7% (n = 7/15) having a definite molecular diagnosis and 6.7% (n = 1/15) having a likely molecular diagnosis. We discuss this in the context of a rare disease in general and specifically SD presentations. Of patients with known diagnoses pre-WES (n = 10), molecular confirmation occurred in 7/10 cases, as opposed to 1/5 where a diagnosis was unknown pre-test. Thus, diagnostic return is greatest where the diagnosis is known pre-test. For WGS (whole genome sequencing, the next iteration of WES), careful case selection (ideally of known diagnoses pre-test) will yield highest returns. CONCLUSIONS: Our results highlight the cost-effective use of WES-targeted bioinformatic analysis as a diagnostic tool for SD, particularly patients with presumed SD, where detailed phenotyping is essential. Thorough co-ordinated clinical evaluation between clinical, radiological, and molecular teams is essential for improved yield and clinical care. WES (and WGS) yields will increase with time, allowing faster diagnoses, avoiding needless investigations, ensuring individualised patient care and patient reassurance. Further diagnoses will lead to increased information on natural history/mechanistic details, and likely increased therapies and clinical trials.

Rationale, design, and methods of a randomized, controlled, open-label clinical trial with open-label extension to investigate the safety of vosoritide in infants, and young children with achondroplasia at risk of requiring cervicomedullary decompression surgery.

Achondroplasia causes narrowing of the foramen magnum and the spinal canal leading to increased mortality due to cervicomedullary compression in infants and significant morbidity due to spinal stenosis later in adulthood. Vosoritide is a C-natriuretic peptide analogue that has been shown to improve endochondral ossification in children with achondroplasia. The objective of this trial is to evaluate the safety of vosoritide and whether vosoritide can improve the growth of the foramen magnum and spinal canal in children that may require decompression surgery. An Achondroplasia Foramen Magnum Score will be used to identify infants at risk of requiring decompression surgery. This is a 2-year open label randomized controlled trial of vosoritide in infants with achondroplasia ages 0 to ≤12 months. Approximately 20 infants will be randomized 1:1 to either open label once daily subcutaneous vosoritide combined with standard of care or standard of care alone. The primary and secondary aims of the study are to evaluate the safety and efficacy of vosoritide in children with cervicomedullary compression at risk of requiring decompression surgery. The trial will be carried out in specialized skeletal dysplasia treatment centers with well established multidisciplinary care pathways and standardized approaches to the neurosurgical management of cervicomedually compression. After 2 years, infants randomized to standard of care alone will be eligible to switch to vosoritide plus standard of care for an additional 3 years. This pioneering trial hopes to address the important question as to whether treatment with vosoritide at an early age in infants at risk of requiring cervicomedullary decompression surgery is safe, and can improve growth at the foramen magnum and spinal canal alleviating stenosis. This in turn may reduce compression of surrounding structures including the neuraxis and spinal cord, which could alleviate future morbidity and mortality.Trial registrations: ClinicalTrials.gov, NCT04554940; EudraCT number, 2020-001055-40.

Lifetime impact of achondroplasia: Current evidence and perspectives on the natural history.

Achondroplasia, the most common form of disproportionate short stature, is caused by a variant in the fibroblast growth factor receptor 3 (FGFR3) gene. Advances in drug treatment for achondroplasia have underscored the need to better understand the natural history of this condition. This article provides a critical review and discussion of the natural history of achondroplasia based on current literature evidence and the perspectives of clinicians with extensive knowledge and practical experience in managing individuals with this diagnosis. This review draws evidence from recent and ongoing longitudinal natural history studies, supplemented with relevant cross-sectional studies where longitudinal research is lacking, to summarize the current knowledge on the nature, incidence, chronology, and interrelationships of achondroplasia-related comorbidities across the lifespan. When possible, data related to adults are presented separately from data specific to children and adolescents. Gaps in knowledge regarding clinical care are identified and areas for future research are recommended and discussed.

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.

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.

The radiologic diagnosis of skeletal dysplasias: past, present and future.

Skeletal dysplasias have been recognised since recorded history began. The advent of radiography at the beginning of the 20th century and the subsequent introduction of departments of radiology have had tremendous impact and allowed conditions to be identified by their specific radiographic phenotypes. This has been enhanced by the addition of cross-sectional modalities (ultrasound, computed tomography and magnetic resonance imaging), which have allowed for prenatal recognition and diagnosis of skeletal dysplasias, and by the recent explosion in identified genes. There are more than 400 recognised skeletal dysplasias, many of which (due to their rarity) the practising clinician (radiologist, paediatrician, geneticist) may never come across. This article provides a historical overview of aids to the radiologic diagnosis of skeletal dysplasias.

Expanding the phenotypic spectrum of IFT81: Associated ciliopathy syndrome.

Short-rib polydactyly syndromes are a heterogeneous group of disorders characterized by narrow thorax with short ribs, polydactyly and often other visceral and skeletal malformations. To date there have only been six reported patients with homozygous and compound heterozygous variants in IFT81, causing a short-rib thoracic dysplasia, with, or without, polydactyly (SRTD19: OMIM 617895). IFT81 is a protein integral to the core of the intraflagellar transport complex B (IFT-B), which is involved in anterograde transport in the cilium. We describe the case of a male infant with compound heterozygous variants in IFT81, who presented with short long bones, a narrow thorax, polydactyly, and multiple malformations. Three novel clinical features are reported including complete situs inversus, micropenis, and rectal atresia, which have not previously been associated with variants in IFT81. We reviewed the literature and identified the most consistent clinical features associated with this rare ciliopathy syndrome. We postulate that dolichocephaly and sagittal craniosynostosis may be associated with this condition, and provide a clue to considering IFT81 as the causative gene when deciphering complex ciliopathies.

Whole-body MRI in the diagnosis of paediatric CNO/CRMO.

Chronic recurrent multifocal osteomyelitis (CRMO) is an auto-inflammatory disorder affecting the skeleton of children and adolescents. Whole-body MRI (WBMRI) is key in the diagnosis and follow-up of CRMO. Imaging protocols should include sagittal short Tau inversion recovery of the spine, imaging of the hands and feet, and T1 images for distinguishing normal bone marrow. CRMO lesions can be metaphyseal, epiphyseal and physeal-potentially causing growth disturbance and deformity. Spinal lesions are common, important and can cause vertebral collapse. Lesion patterns include multifocal tibial and pauci-focal patterns that follow a predictable presentation and course of disease. Common pitfalls of WBMRI include haematopoietic marrow signal, metaphyseal signal early on in bisphosphonate therapy and normal high T2 signal in the hands and feet. Pictorial reporting assists in recording lesions and follow-up over time. The purpose of this paper is to review the different WBMRI protocols, imaging findings, lesion patterns and common pitfalls in children with CRMO.