Miyagi Children's Hospital

Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) is a congenital disorder characterized by lymphedema, telangiectasia, and hypotrichosis or alopecia, caused by mutations in the SRY-related high-mobility group box (SOX) 18 gene. We report the case of a 10-year-old boy who presented with aortic valve regurgitation, marbled skin, minor anomalies, and iron-deficiency anemia due to frequent mucosal bleeding. At 5 years of age, he experienced significant hemostatic difficulties following the extraction of a deciduous tooth. The usual doses of iron supplementation did not cure his iron-deficiency anemia. Blood coagulation analysis revealed a decreased platelet agglutination capacity, associated with reduced von Willebrand factor (vWF) antigen levels and activity. Whole-genome sequencing at the age of 15 years did not identify any pathogenic variants in the VWF gene. However, this analysis revealed a heterozygous pathogenic variant of SOX18 (NM_018419.3: c.481C>T, p.Gln161Ter), which led to the diagnosis of HLTS. SOX18 plays a significant role in VWF expression in stem cells. vWF replacement therapy facilitated safe tooth extraction and stabilized hemoglobin levels. Decreased vWF may be a complication of HLTS, and vWF replacement therapy can significantly improve patients' quality of life.

小児のためのアトピー性皮膚炎の予防と治療の手引き～小児アトピー性皮膚炎治療・管理ガイドライン2024～の第III章では，鑑別診断・重症度評価について概説されている．アトピー性皮膚炎の治療選択とその効果判定には，重症度を正しく評価することが欠かせない．バイオマーカーとしては，血清thymus and activation regulated chemokine（TARC）値，血清squamous cell carcinoma antigen 2（SCCA2）値が主に用いられ，医師による評価法は，日常臨床では簡便なinvestigator's global assessment（IGA）を用い，全身療法を考慮する患者ではさらにeczema area and severity index（EASI）が用いられる．また，アトピー性皮膚炎として個疹の特徴や抗炎症外用薬等への反応性に違和感がある場合は，常にアトピー性皮膚炎以外の疾患との鑑別を繰り返す必要がある．

SummaryWe report the case of a male infant born at 37 weeks and 4 days of gestation with a birth weight of 3396 g. He presented with hypotonia, congenital heart disease, heterotaxy and polydactyly. Based on physical examination and brain MRI, which revealed the characteristic molar tooth sign, he was diagnosed with Joubert syndrome and related disorders (JSRD). He experienced repeated episodes of atelectasis, making extubation challenging. Electron microscopy revealed ciliary structural abnormalities, leading to the diagnosis of primary ciliary dyskinesia as well as JSRD. Despite multiple medical interventions and two surgical procedures for heart failure, he died at 10 months old due to progressing chronic heart failure and pulmonary infections.This report presents the course leading to the diagnosis of ciliary dysfunction-associated multiple malformations, based on the diverse symptoms. Furthermore, we discuss the potential risk of postoperative complications associated with ciliary dysfunction.

Aim: To report the efficacy and safety of ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) from the phase III, 72-week, placebo-controlled period of Study 041. Materials & methods: Inclusion criteria: boys with nmDMD aged ≥5years, on a stable corticosteroid regimen for ≥12months, and baseline 6-minute walk distance (6MWD) ≥150m. Randomization: 1:1, ataluren (40mg/kg/day):placebo. Primary end point: slope of 6MWD change (average rate of change). Secondary end points: changes in 6MWD, time to 10% persistent worsening in 6MWD, North Star Ambulatory Assessment score, timed function tests and safety. Study populations: intention-to-treat; patients aged ≥7 to ≤16years with baseline 6MWD ≥300m and stand from supine ≥5s; patients with baseline 6MWD 300-400m. Results: In the intention-to-treat population (n=359), over 72weeks, ataluren reduced the rate of 6MWD decline by 21% (p = 0.0248), reduced the average 6MWD change (p = 0.0248), delayed time to 10% persistent worsening in 6MWD (p = 0.0078), and reduced North Star Ambulatory Assessment total score decline (p = 0.0235), change in 10m walk/run time (p=0.0422) and change in time to climb four stairs (p = 0.0293) versus placebo. In the 6MWD 300-400m subgroup (n=169), ataluren reduced the rate of 6MWD decline by 30% (p = 0.0310) versus placebo. Ataluren treatment benefits were seen in secondary end points in this subgroup, except for change in time to descend four stairs. In the 6MWD ≥300m and time to stand from supine ≥5s subgroup (n=185), there was a 9% slower rate of 6MWD decline for ataluren versus placebo over 72weeks (p = 0.3626). Ataluren reduced change in time to climb four stairs (p = 0.0179) versus placebo in this subgroup; no treatment benefits were seen for other secondary end points. Ataluren was well tolerated (serious adverse events: ataluren, 7.1%; placebo, 6.8%); no deaths occurred. Conclusion: Long-term ataluren treatment has a favorable benefit-risk profile, slowing motor function decline in the largest phase III nmDMD study to date.

Inflammatory bowel disease (IBD) can occur at any age. In pediatric patients, the disease may present with a broader range of symptoms and more severe course than in adults, due to ongoing growth and development. Therefore, pediatric IBD often exhibits an atypical clinical course and laboratory findings. It is essential to recognize differences in disease presentation, differential diagnoses, and evaluation strategies specific to children. The revised Porto criteria, proposed by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) in 2014, are widely used globally, including in Japan, for the diagnosis of pediatric IBD. Despite the widespread use of these criteria, no formal diagnostic guidelines for pediatric IBD have been developed in Japan. We aimed to support future guideline development by summarizing important diagnostic considerations and clinical practices for pediatric IBD in Japan. This review was developed based on relevant international diagnostic guidelines and the expert opinions of Japanese pediatric gastroenterologists. It outlines key clinical and laboratory evaluations, as well as current treatment and follow-up approaches. We summarized recommended diagnostic tests and clinical points that require special attention in children with suspected IBD. The article reflects both global standards and domestic clinical experience. Although this article does not provide formal diagnostic criteria or assess evidence levels, it offers accurate and practical information to guide physicians and patients in the diagnosis and management of pediatric IBD in Japan.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions. There is an urgent need to establish objective, simple, and accurate screening and diagnostic methods for ASD in childhood. Recently, the ability to visualize and quantify eye movements has emerged, suggesting that ASD may exhibit characteristic gaze patterns. To examine the potential of gaze patterns as an early marker of ASD, we analyzed the relationship between gaze patterns at ages 4-6 and individual ASD characteristics, as determined by the Autism Spectrum Quotient Japanese version for children (AQ-J-child) at age 6, using data from 4- to 6-year-old children recruited into the BirThree Cohort Study of the Tohoku Medical Megabank Project. The median gaze rate, which represents the percentage of time the subjects spent looking at the screen during the test, was 92%, reflecting the highly versatile nature and proper execution of this test in our study. We found that children with social impairment tend to prefer looking at geometric patterns. In addition, children with communication difficulties tend to spend less time looking at the eyes in still images of human faces. Our analyses of the relationships between various gaze results and ASD characteristics defined by AQ-J-child revealed that specific gaze preferences are significantly associated with communication difficulties, social impairment, and impaired imagination. These findings indicate that the gaze measurement results show strong correlations with specific aspects of ASD. Therefore, gaze patterns demonstrate the potential to reflect one aspect of ASD.