Multi-gene panel sequencing in highly consanguineous families and patients with congenital forms of skeletal dysplasias.

Skeletal dysplasias (SKDs) are a heterogeneous group of more than 750 genetic disorders characterized by abnormal development, growth, and maintenance of bones or cartilage in the human skeleton. SKDs are often caused by variants in early patterning genes and in many cases part of multiple malformation syndromes and occur in combination with non-skeletal phenotypes. The aim of this study was to investigate the underlying genetic cause of congenital SKDs in highly consanguineous Pakistani families, as well as in sporadic and familial SKD cases from India using multigene panel sequencing analysis. Therefore, we performed panel sequencing of 386 bone-related genes in 7 highly consanguineous families from Pakistan and 27 cases from India affected with SKDs. In the highly consanguineous families, we were able to identify the underlying genetic cause in five out of seven families, resulting in a diagnostic yield of 71%. Whereas, in the sporadic and familial SKD cases, we identified 12 causative variants, corresponding to a diagnostic yield of 44%. The genetic heterogeneity in our cohorts was very high and we were able to detect various types of variants, including missense, nonsense, and frameshift variants, across multiple genes known to cause different types of SKDs. In conclusion, panel sequencing proved to be a highly effective way to decipher the genetic basis of SKDs in highly consanguineous families as well as sporadic and or familial cases from South Asia. Furthermore, our findings expand the allelic spectrum of skeletal dysplasias.

Cytomorphologic and immunocytochemical characterization of pediatric pleuropulmonary blastoma with a comprehensive review of the literature.

INTRODUCTION: Pleuropulmonary blastoma (PPB) is a rare, aggressive, primary intrathoracic malignancy typically seen in infancy and early childhood. Accurate distinction from congenital cystic lung lesions is crucial due to significant prognostic and therapeutic differences. Cytologic features have rarely been described. Establishing a cytodiagnosis is challenging owing to its rarity, lack of awareness, and multiple morphologic mimics. MATERIALS AND METHODS: This was a retrospective study conducted over 8 years. The histopathology and cytopathology databases were searched for all pediatric PPB cases. The corresponding cytologic samples were reviewed to identify characteristic features that can help distinguish PPB from its mimics. RESULTS: There was a total of six cases of pediatric PPB reported during the study period. Of these, four (66.7%) presented as intrathoracic, and two (33.3%) as pleural-based masses. Cytology smears showed discretely scattered and perivascular arrangements of round-oval tumor cells with background eosinophilic stromal material. The tumor cells were mildly pleomorphic (n = 3) with round nuclei, fine chromatin, inconspicuous nucleoli, and scanty cytoplasm; however, three cases showed marked anaplasia, and one each showed necrosis and rhabdoid differentiation. On immunocytochemistry (4/6), these were positive for vimentin and desmin and negative for WT1, chromogranin, SALL4, cytokeratin, CD45, and CD99. FISH (1/6) did not show N-Myc amplification. CONCLUSIONS: Knowledge of the characteristic cytomorphological and immunocytochemical features of PPB is vital to establish a prompt and accurate cytodiagnosis with appropriate clinicoradiologic correlation.

Canal of nuck hernia with uterus and ovary presenting as inguinal swelling in a female infant.

Canal of nuck hernia is rarely reported in pediatric population. We report one such case of a canal of nuck hernia in a 2-month-old girl containing uterus, ovary and small bowel diagnosed on ultrasonography, and which was later confirmed and treated surgically.

Pneumatic Insufflation to Confirm Distal Stoma When in Doubt.

Background Distal colostogram and ileostogram are commonly performed radiological procedures in the pediatric population. It is sometimes difficult to identify the distal stoma while performing these procedures. Aim The aim of this study was to describe a technique for the confident identification of distal stoma. Methods Injection of a small quantity of air through the catheterized stoma and following it can help to identify the stoma, as proximal or distal, based on anatomy of the delineated bowel. Conclusion Pneumatic insufflation is a simple, quick procedure to confidently identify the distal stoma whenever in doubt.

Unusual pediatric lung infections: imaging findings.

Pediatric lung infections continue to be a leading cause of pediatric morbidity and mortality. Although both pediatric and general radiologists are familiar with typical lung infections and their imaging findings in children, relatively rare lung infections continue to present a diagnostic challenge. In addition, the advances in radiological imaging and emergence of several new lung infections in recent years facilitated the need for up-to-date knowledge on this topic. In this review article, we discuss the imaging findings of pediatric lung infections caused by unusual/uncommon and new pathogens. We review the epidemiological, clinical, and radiological imaging findings of viral (coronavirus disease 2019, Middle East respiratory syndrome, bird flu), bacterial (Streptococcus anginosus, Francisella tularensis, Chlamydia psittaci), and parasitic lung infections (echinococcosis, paragonimiasis, amoebiasis). Additional disorders whose clinical course and imaging findings may mimic lung infections in children (hypersensitivity pneumonitis, pulmonary hemorrhage, eosinophilic pneumonia) are also presented, to aid in differential diagnosis. As the clinical presentation of children with new and unusual lung infections is often non-specific, imaging evaluation plays an important role in initial detection, follow-up for disease progression, and assessment of potential complications.

Shear wave elastography of kidneys in children: utility in distinguishing steroid-resistant and steroid-sensitive nephrotic syndrome.

PURPOSE: To assess the renal elasticity values using (SWE) and correlate the values with steroid sensitivity to distinguish between steroid-resistant nephrotic syndrome (SRNS) and steroid-sensitive nephrotic syndrome (SSNS) in children. METHODS: In this IRB-approved cross-sectional study, 83 children (4-14 years) diagnosed with nephrotic syndrome were included from July 2021 to December 2022. SWE measurements were done for each kidney's upper pole, interpolar region, and lower pole. Mean as well as median SWE were calculated. Correlation of the renal stiffness values was done with different laboratory findings (blood urea, serum creatinine, 24 h urine protein, serum albumin, and serum cholesterol), the grayscale findings (cortical echogenicity, and corticomedullary differentiation), and the final diagnosis of SRNS and SSNS. The statistical tests were done at a significance level of α = 0.05. RESULTS: The median (IQR) overall SWE of kidneys was higher in SRNS group 12.64 (8.4-19.68) kPa than SSNS group 9.87 (8.20-12.56) kPa. The difference was significant (p = 0.004). At a cut-off of ≥ 10.694 kPa (AUROC- 0.641), the overall SWE predicted SRNS group with a sensitivity of 70% and a specificity of 63%. A significant correlation (p < 0.05) was found between the SWE and 24-h urine protein, cortical echogenicity, and corticomedullary differentiation in SSNS, while only between SWE and corticomedullary differentiation in SRNS. CONCLUSION: The mean SWE was higher in children with SRNS. While SWE has potential to differentiate SSNS from SRNS, a different study design where SWE is performed at presentation is needed for confirmation.

Ultrasound and magnetic resonance imaging in thoracic tuberculosis in the pediatric population: moving beyond conventional radiology.

Imaging is crucial in the diagnostic work-up and follow-up after treatment in children with thoracic tuberculosis (TB). Despite various technological advances in imaging modalities, chest radiography is the primary imaging modality for initial care and in emergency settings, especially in rural areas and where resources are limited. Ultrasonography (US) of the thorax in TB is one of the emerging applications of US as a radiation-free modality in children. Magnetic resonance imaging (MRI) is the ideal radiation-free, emerging imaging modality for thoracic TB in children. However, only limited published data is available regarding the utility of MRI in thoracic TB. In this pictorial review, we demonstrate the use of US and rapid lung MRI in evaluating children with thoracic TB, specifically for mediastinal lymphadenopathy and pulmonary complications of TB.

2D Shear wave elastography for evaluation of renal cortex and medulla: stiffness values in healthy children.

PURPOSE: To evaluate renal cortical and medullary stiffness using 2D Shear-wave elastography (SWE) in healthy children. METHODS: In this IRB approved prospective study, we measured the stiffness of cortex and medulla of children (4 months-17 years) at the upper pole, mid pole, and lower pole in bilateral kidneys. RESULTS: The median (IQR) values of renal cortex in <1 year age group was 8.7 (5.7-11.7) kPa for right and 8.7 (4.2-14.1) kPa for the left side. For 1-5 years age group, it was 7.3 (5.3-10) kPa for the right and 8.9 (6-12.3) kPa for the left side. For >5 years, it was 7.4 (5.3-11.2) kPa for the right and 9.6 (6.2-12.7) kPa for the left side. The median (IQR) values of renal medulla in <1 year age group was 7.1 (5.1-12.5) kPa for right and 6.8 (4-10.6) kPa for the left side. For 1-5 years age group, it was 7.2 (4.9-9.7) kPa for the right and 6.9 (5.6-9.9) kPa for the left side. For >5 years, it was 6.8 (5.1-9.6) kPa for the right and 7 (5-10.2) kPa for the left side. The differences in the elasticity values amongst these groups were statistically insignificant (p>0.05). There was a significant correlation between SWE values of cortex and medulla of right kidney (ρ=0.64) and of left kidney (ρ=0.61), respectively. CONCLUSION: SWE values of renal cortical and medullary stiffness in healthy children do not correlate with age. There is a significant correlation between SWE values of cortex and medulla of the kidneys in healthy children.

Radiological Imaging in Chest Diseases: Moving Away from Conventional Modes.

A chest radiograph is the most common and the initial radiological investigation for evaluating a child presenting with respiratory complaints. However, performing and interpreting chest radiography optimally requires training and skill. With the relatively easy availability of computed tomography (CT) scanning and more recently multidetector computed tomography (MDCT), these investigations are often performed. Although these can be the cross-sectional imaging modalities of choice in certain situations where detailed and exact anatomical and etiological information is required, both these investigations are associated with increased radiation exposure which has more detrimental effects on children, especially when repeated follow-up imaging is necessary to assess the disease status. Ultrasonography (USG) and magnetic resonance imaging (MRI) have evolved as radiation-free radiological investigations for evaluating the pediatric chest pathologies over the last few years. In the present review article, the utility and the current status, as well as the limitations of USG and MRI for evaluation of pediatric chest pathologies, are discussed. Radiology has grown beyond having just the diagnostic capabilities in managing children with chest disorders in the last two decades. Image-guided therapeutic procedures (percutaneous and endovascular) are routinely performed in children with pathologies in the mediastinum and lungs. The commonly performed image-guided pediatric chest interventions, including biopsies, fine needle aspiration, drainage procedures and therapeutic endovascular procedures, are also discussed in the current review.

Tuberculosis revisted: classic imaging findings in childhood.

Tuberculosis (TB) remains one of the major public health threats worldwide, despite improved diagnostic and therapeutic methods. Tuberculosis is one of the main causes of infectious disease in the chest and is associated with substantial morbidity and mortality in paediatric populations, particularly in low- and middle-income countries. Due to the difficulty in obtaining microbiological confirmation of pulmonary TB in children, diagnosis often relies on a combination of clinical and radiological findings. The early diagnosis of central nervous system TB is challenging with presumptive diagnosis heavily reliant on imaging. Brain infection can present as a diffuse exudative basal leptomeningitis or as localised disease (tuberculoma, abscess, cerebritis). Spinal TB may present as radiculomyelitis, spinal tuberculoma or abscess or epidural phlegmon. Musculoskeletal manifestation accounts for 10% of extrapulmonary presentations but is easily overlooked with its insidious clinical course and non-specific imaging findings. Common musculoskeletal manifestations of TB include spondylitis, arthritis and osteomyelitis, while tenosynovitis and bursitis are less common. Abdominal TB presents with a triad of pain, fever and weight loss. Abdominal TB may occur in various forms, as tuberculous lymphadenopathy or peritoneal, gastrointestinal or visceral TB. Chest radiographs should be performed, as approximately 15% to 25% of children with abdominal TB have concomitant pulmonary infection. Urogenital TB is rare in children. This article will review the classic radiological findings in childhood TB in each of the major systems in order of clinical prevalence, namely chest, central nervous system, spine, musculoskeletal, abdomen and genitourinary system.

Imaging recommendations and algorithms for pediatric tuberculosis: part 1-thoracic tuberculosis.

Tuberculosis (TB) remains a global health problem and is the second leading cause of death from a single infectious agent, behind the novel coronavirus disease of 2019. Children are amongst the most vulnerable groups affected by TB, and imaging manifestations are different in children when compared to adults. TB primarily involves the lungs and mediastinal lymph nodes. Clinical history, physical examination, laboratory examinations and various medical imaging tools are combined to establish the diagnosis. Even though chest radiography is the accepted initial radiological imaging modality for the evaluation of children with TB, this paper, the first of two parts, aims to discuss the advantages and limitations of the various medical imaging modalities and to provide recommendations on which is most appropriate for the initial diagnosis and assessment of possible complications of pulmonary TB in children. Practical, evidence-based imaging algorithms are also presented.

Imaging recommendations and algorithms for pediatric tuberculosis: part 2-extrathoracic tuberculosis.

Despite advances in diagnosis and treatment in recent years, tuberculosis (TB) remains a global health concern. Children are amongst the most vulnerable groups affected by this disease. Although TB primarily involves the lungs and mediastinal lymph nodes, it can affect virtually any organ system of the body. Along with clinical history combined with physical examination and laboratory tests, various medical imaging tools help establish the diagnosis. Medical imaging tests are also helpful for follow-up during therapy, to assess complications and exclude other underlying pathologies. This article aims to discuss the utility, strengths and limitations of medical imaging tools in the evaluation of suspected extrathoracic TB in the pediatric population. Imaging recommendations for the diagnosis will be presented along with practical and evidence-based imaging algorithms to serve as a guide for both radiologists and clinicians.

Impact of Radial Percentage K-Space Filling and Signal Averaging on Native Lung MRI Image Quality in 3D Radial UTE Acquisition: A Pilot Study.

RATIONALE AND OBJECTIVE: To assess the impact of radial percentage k-space filling and signal averaging on lung MRI image quality in 3D radial ultrashort echo-time (UTE) acquisition. MATERIALS AND METHODS: In this IRB approved prospective study, 25 patients (10-30 years) referred for MRI examination for indications other than related to lungs were enrolled from January 2021 to November 2021. All the patients underwent lung MRI, using three different UTE sequence parameters with radial (R) percentage of 100 or 200 and number of signal averages (NSA) of one or two. Two radiologists independently assessed the images for the outline of pleural and mediastinal surface, visibility of lung parenchyma, major bronchi, and segmental bronchi. The quality of the images was assessed based on the degree of motion artifacts. For objective assessment, signal-to-noise ratio, contrast-to-noise ratio, and contrast ratio were calculated. RESULTS: The outline of pleural and mediastinal surface, lung parenchyma, and segmental bronchi were best demonstrated on R100_NSA2 sequence. The major bronchi were best demonstrated on R100_NSA2 and R100_NSA1 sequences. The intersequence difference was statistically significant for evaluating the pleural and mediastinal surface and segmental bronchi only (p < 0.05). Overall, the best image quality with least artifacts was seen with R100_NSA2 sequence. The objective assessment showed no statistically significant difference between the three sequences (p > 0.05). Interobserver agreement for different findings was substantial to almost perfect for R100_NSA2 and R200_NSA1 sequences. CONCLUSION: R100_NSA2 UTE sequence performed best for the evaluation of the different findings and showed the best image quality.

Utility of the New Faster Compressed SENSE MRCP at 3 Tesla MRI in Children with Pancreatitis.

OBJECTIVE: To compare the acquisition time, diagnostic efficacy, and image quality of the newer compressed SENSE 3D MRCP (CS-3D MRCP) with conventional 3D MRCP (C-3D MRCP) in children with pancreatitis. METHODS: A total of 24 children (2-17 y) diagnosed with pancreatitis were included in this study. The children underwent CS-3D MRCP and C-3D MRCP sequences. C-3D MRCP and CS-3D MRCP images were evaluated for the acquisition time duration, visualization of the pancreaticobiliary ducts, background suppression, image quality degradation by artifacts, and overall image quality by the two radiologists independently. Paired sample t-test was used to compare the acquisition time, the McNemar test for the image quality features, and the kappa coefficient was used for interobserver agreement. RESULTS: A two-fold decrease in the acquisition time of CS-3D MRCP (~148 ± 61 s) was seen, compared to C-3D MRCP (~310 ± 98 s), p < 0.001. The median scores for overall image quality on CS-3D MRCP and C-3D MRCP, respectively, were 2.05 ± 0.52 and 2.21 ± 0.53 (p = 0.18) for both radiologists. No significant difference was seen for the visibility of ducts, background suppression, and artifacts between the two radiologists, with substantial to almost perfect agreement seen for the different findings. CONCLUSION: The application of compressed SENSE 3D MRCP in children with pancreatitis results in a two-fold reduction in acquisition time with acceptable image quality. This may help in reducing the need for long sedation in children requiring anesthesia support for the MRCP and potentially help in reducing motion artifacts.