Haploinsufficiency of NKX2-1 is likely to contribute to developmental delay involving 14q13 microdeletions.

Nucleotide variations or deletions in the NK2 homeobox 1 gene (NKX2-1), located at 14q13.3, lead to symptoms associated with the brain, lungs, and thyroid, and the combination of these phenotypes is clinically recognized as the brain-lung-thyroid syndrome. Many types of nucleotide variants of NKX2-1 have been identified, and phenotypic variability has been reported. Chromosomal deletions involving NKX2-1 have also been reported; however, phenotypic differences between patients with nucleotide variants of NKX2-1 and patients with chromosomal deletions involving NKX2-1 have not been well established. Recently, we identified seven patients with 14q13 microdeletions involving the NKX2-1. Most patients exhibited developmental delay. This inquiry arises regarding the potential existence of haploinsufficiency effects beyond those attributed to NKX2-1 within the 14q13 microdeletion. However, a literature review has shown that developmental delay is not rare in patients with nucleotide alterations in NKX2-1. Rather, motor function impairment may have affected the total developmental assessment, and the haploinsufficiency of genes contiguous to NKX2-1 is unlikely to contribute to developmental delay.

Pediatric allergies in Japan: Coronavirus disease pandemic-related risk factors.

Background: The coronavirus disease 2019 (COVID-19) pandemic impacted various parts of society, including Japanese children with allergies. Objective: This study investigated risk factors for pediatric allergic diseases associated with the state of emergency owing to the COVID-19 pandemic in Japan, including during school closures. Methods: Parents of pediatric patients (0-15 years) with allergies were enrolled and queried regarding the impact of school closure on pediatric allergies compared to that before the COVID-19 pandemic. Results: A valid response was obtained from 2302 parents; 1740 of them had children with food allergies. Approximately 4% (62/1740) of the parents reported accidental food allergen ingestion was increased compared to that before the COVID-19 pandemic. Accidental ingestion during school closures was associated with increased contact with meals containing allergens meant for siblings or other members of the family at home. The exacerbation rate during the pandemic was highest for atopic dermatitis at 13% (127/976), followed by allergic rhinitis at 8% (58/697), and bronchial asthma at 4% (27/757). The main risk factors for worsening atopic dermatitis, allergic rhinitis, and bronchial asthma were contact dermatitis of the mask area (34/120 total comments); home allergens, such as mites, dogs, and cats (15/51 total comments); and seasonal changes (6/25 total comments), respectively. Conclusion: The main factors affecting allergic diseases were likely related to increased time at home, preventive measures against COVID-19, and refraining from doctor visits. Children with allergies were affected by changes in social conditions; however, some factors, such as preventing accidental ingestion and the management of allergens at home, were similar to those before the COVID-19 pandemic. Patients who had received instructions on allergen avoidance at home before the pandemic were able to manage their disease better even when their social conditions changed.

Development of an Oral Immunotherapy-Related Parental Burden Scale.

INTRODUCTION: Oral immunotherapy (OIT) imposes a burden on parents and their children with food allergies (FAs). We already developed a questionnaire for OIT-related Parental Burden (OIT-PB) scale. However, the previous questionnaire had some problems. This study modified OIT-PB and verified its reliability and validity. METHODS: A 20-item draft covering the physical and mental burdens caused by OIT was prepared jointly with multiple allergists. The Food Allergy Quality of Life Questionnaire-Parental Burden (FAQLQ-PB) and Stress Response Scale-18 (SRS-18) were used to verify concurrent validity. A questionnaire survey was administered during treatment to parents of FA children who had started OIT for the first time. An additional OIT-PB survey was performed at one specific institution 1 week after the posttreatment survey. RESULTS: The responses of 64 of the 76 recruited parents were analyzed. Of the 20 questions, 1 item was excluded owing to the floor effect, 1 was excluded because its commonality was less than 0.2, and 2 were excluded because their factor loading values were less than 0.4. Factor analysis was used to classify the OIT-PB into the following 4 subscales: "burden caused by adherence to treatment plan," "anxiety about symptom-induced risk," "burden due to patient's eating behavior," and "anxiety about treatment effect." The Cronbach's α for all 16 items of the OIT-PB was 0.893; Cronbach's α for each subscale was 0.876, 0.898, 0.874, and 0.717. The re-test reliability coefficient was 0.864 (95% confidence interval [CI]: 0.720-0.937, p < 0.001). A significant positive correlation was found between the OIT-PB and FAQLQ-PB (R = 0.610 [95% CI: 0.422-0.747], p < 0.001) and the SRS-18 (R = 0.522 [95% CI: 0.306-0.687], p < 0.001). A significant negative correlation was found between the rate of increase in OIT food intake and the "anxiety about treatment effect" score (R = -0.355 [95% CI: -0.558-0.112], p < 0.001). Parents of children on the hen's egg OIT treatment scored higher on the "burden due to patient's eating behavior" subscale than did parents of children on the milk and wheat OIT treatment. CONCLUSION: The burden of OIT experienced by parents can be broadly classified into four categories. The modified OIT-PB was able to evaluate them individually and was shown to have reliability and validity. This scale is expected to be useful in the development of OIT that considers not only therapeutic effect but also the burden experienced by FA children and their parents.

Rare case of Stevens-Johnson syndrome with bronchiolitis obliterans as a chronic complication.

A young girl in her teens presented with fever, rashes and various mucocutaneous symptoms. Flat erythematous macules were seen mainly on the limbs, without blisters or skin detachments. The lips were swollen with crusts and haemorrhage. The oral cavity and pharynx showed ulcerative lesions with exudate. Severe bilateral ocular lesions with pseudomembrane formation and corneal epithelial defects were present. Also, urogenital lesion and gastrointestinal symptoms with frequent haematochezia were observed. Her symptoms and pathological findings were consistent with Stevens-Johnson syndrome. She was treated with prednisolone and methylprednisolone pulse therapy. Her ocular and cutaneous symptoms improved without severe chronic complications. However, 1 month later, she developed dyspnoea, and a pulmonary function test revealed severe obstructive ventilation disorder. After discharge, she was regularly followed up for respiratory complications. High-resolution chest CT performed 9 months after onset revealed mosaic perfusions and bronchiectasis, consistent with bronchiolitis obliterans.

A rare case of retroperitoneal teratoma with obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome.

A 9-month-old girl presented with progressive abdominal distension. Imaging revealed a huge cystic mass in the left retroperitoneum with solid components. The right kidney was absent and hydrometrocolpos was found. Tumour drainage and complete surgical excision were performed. A bulge in the right side of the uterus, suggestive of a uterine anomaly, was seen on laparoscopic observation. Pathology was consistent with teratoma with a small portion of immature neural tissue. The patient was discharged in good condition and was advised regular follow-up.

Infantile Inflammatory Bowel Disease in a Three-Month-Old-Boy.

Very early-onset inflammatory bowel disease (VEO-IBD) and infantile IBD occur in children aged less than six years and less than two years, respectively. Since childhood-onset IBD seems to be a more aggressive and rapidly progressive disease than adult-onset IBD, it should therefore be diagnosed and treated immediately. Here, we report a case of infantile IBD in a three-month-old infant with clinical and biochemical manifestations. The diagnosis was confirmed with histopathological evidence. The patient had been treated successfully with both mesalazine and prednisolone and with mesalazine alone on follow-up.

Left retroperitoneal abscess caused by injury of the right knee.

Minor trauma rarely triggers a retroperitoneal abscess. The patient' history, careful evaluation of their symptoms, and general examination with a detailed inspection of the skin are helpful to diagnose retroperitoneal abscess.

Serum cytokine profile in pediatric Sweet's syndrome: a case report.

BACKGROUND: Sweet's syndrome is characterized by fever, leukocytosis, and tender erythematous papules or nodules. It is a rare condition, particularly in the pediatric population, and has recently been proposed to be an autoinflammatory disease that occurs due to innate immune system dysfunction, involving several cytokines, which causes abnormally increased inflammation. To the best of our knowledge, no report has documented the cytokine profile in a pediatric patient with Sweet's syndrome. CASE PRESENTATION: A previously healthy 34-month-old Japanese girl was hospitalized because of remittent fever and pain in her right lower extremity with erythematous nodules. A skin biopsy of the eruption revealed dermal perivascular neutrophilic infiltration with no evidence of vasculitis, which led to the diagnosis of Sweet's syndrome. She was prescribed with orally administered prednisolone and a prompt response was observed; then, the prednisolone dose was tapered. During treatment she developed upper and lower urinary tract infections, after which her cutaneous symptoms failed to improve despite increasing the prednisolone dosage. To avoid long-term use of systemic corticosteroids, orally administered potassium iodide was initiated, but it was unsuccessful. However, orally administered colchicine along with prednisolone effectively ameliorated her symptoms, and prednisolone dosage was reduced again. We analyzed the circulating levels of interleukin-1ß, interleukin-6, interleukin-18, neopterin, and soluble tumor necrosis factor receptors I and II, in order to clarify the pathogenesis of Sweet's syndrome. Of these cytokines, only interleukin-6 levels were elevated prior to orally administered prednisolone therapy. Following therapy, the elevated interleukin-6 levels gradually diminished to almost normal levels; interleukin-1ß and interleukin-18 stayed within normal ranges throughout the treatment. Neopterin became marginally elevated after the start of treatment. Both soluble tumor necrosis factor receptor I and soluble tumor necrosis factor receptor II levels increased shortly after the onset of urinary tract infections. CONCLUSIONS: This is the first case report of pediatric Sweet's syndrome in which serum cytokine levels were investigated. Future studies should gather more evidence to elucidate the pathophysiology of Sweet's syndrome.

A Case of Apparent Life-Threatening Event: Comorbid Gastric Volvulus Associated Gastroesophageal Reflux Disease and Epilepsy in a 4-Month-Old Boy.

Most isolated episodes of apparent life-threatening events (ALTEs) do not lead to the diagnosis of serious conditions, and their prognoses are generally benign. However, recurrent ALTEs are often associated with a risk of future serious adverse events and should be evaluated for appropriate management. Here we present ALTE case in which gastric volvulus associated gastroesophageal reflux disease was detected as an etiology initially, followed by the detection of epilepsy as another etiology. Clinicians should consider possibility of two or more etiologies in a single recurrent ALTE case.

Human parechovirus infections and child myositis cases associated with genotype 3 in Osaka City, Japan, 2014.

Human parechovirus (HPeV) infects humans early in life and typically causes asymptomatic or mild diseases such as gastrointestinal and respiratory illness but sometimes leads to more serious consequences in neonates and young infants. In 2014, we detected HPeV from 38 patients by real-time reverse transcription-PCR in Osaka City, Japan, and 33 HPeV strains were genotyped based on their VP1 sequences. HPeV genotype 3 (HPeV-3) was the most prevalent and accounted for 22 cases (66.7%) followed by nine HPeV-1 (27.3%), one HPeV-2 (3.0%) and one HPeV-4 (3.0%). Phylogenetic analysis revealed that detected HPeV-3 strains were divided into three genetically distinct groups. One was characterized by a novel single amino acid deletion mutation at the N terminus of the 2A protein as well as the VP1 sequence, whereas the others were closely related to HPeV-3 strains detected in Japan in either 2008 or 2011. These HPeV-3 groups were detected from patients with various symptoms including three myositis cases. Recent papers have demonstrated that HPeV-3 was the aetiological agent for epidemic myalgia exclusively among adults from Yamagata Prefecture in Japan. Here, we provide clinical details and episodes of three myositis patients including an adult and two children in Osaka City, Japan. Our results suggest that HPeV-3 is a causative agent of myositis not only in adults but also in children.

An endobronchial inflammatory myofibroblastic tumor in a 10-yr-old child after allogeneic hematopoietic cell transplantation.

IMTs belong to the group of soft tissue tumor and could occur at any anatomical site; however, the causes and growth feature remain unclear. This case report documents a 10-yr-old male suffering from slowly developing dyspnea on exertion and cough around seven months post-HCT. He was diagnosed with an endobronchial tumor based on imaging, and histology confirmed ALK-positive submucosal spindle-shaped cells with infiltrative cells, compatible with IMT. We should be aware that IMT is a potential complication of pediatric allogeneic HCT and can cause sudden airway obstruction.

Congenital dyserythropoietic anemia type 1 with a novel mutation in the CDAN1 gene previously diagnosed as congenital hemolytic anemia.

The congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of genetic disorders of red cell production. They are characterized by ineffective erythropoiesis and dyserythropoiesis. Here, we present the clinical description and mutation analysis of a Japanese female with CDA type 1. She has long been diagnosed with unclassified congenital hemolytic anemia from the neonatal period. However, bone marrow morphology and genetic testing of the CDAN1 gene at the age of 12 years confirmed the afore-mentioned diagnosis. Thus, we should be aware of the possibility of CDA if the etiology of congenital anemia or jaundice cannot be clearly elucidated.