Clinical use of whole exome sequencing in children with developmental delay/intellectual disability.

BACKGROUND: Identifying the underlying etiology of developmental delay/intellectual disability (DD/ID) is challenging but important. The genetic diagnosis of unexplained DD/ID helps in the treatment and prognosis of the disability in patients. In this study, we reported our experience of using whole exome sequencing (WES) of children with unexplained DD/ID. METHODS: We conducted a retrospective analysis of WES results of children under 19 years of age with unexplained DD/ID between January 2020 and December 2021. The demographic data of all patients and variants identified through WES were evaluated. Furthermore, we evaluated the clinical characteristics that influenced the identification of genetic causes. RESULTS: Forty-one patients with DD/ID were included, of whom 21 (51.2 %) were male. The average age at symptom onset was 1.6 ± 1.3 years, and the duration from symptom onset to diagnosis was 3.1 ± 3.7 years. Hypotonia was the most common symptom (17 patients, 41.5 %), and epilepsy was confirmed in 10 patients (24.4 %). Twenty-two pathogenic/likely pathogenic variants were identified in 20 patients, and three variants of uncertain significance were identified in three patients. Family-based trio Sanger sequencing for candidate variants of 12 families was conducted; 10 variants were de novo, one variant paternally inherited, and two variants compound heterozygous. The diagnostic yield of WES for DD/ID was 48.8 % and was significantly high in patients with an early onset of DD/ID and facial dysmorphism. In contrast, patients with autism spectrum disorder (ASD) were more likely to have negative WES results compared with others without ASD. CONCLUSION: The diagnostic yield of WES was 48.8 %. We conclude that patients' characteristics, such as dysmorphic features and the age of symptom onset, can predict the likelihood that WES will identify a causal variant of a phenotype.

Pontocerebellar Hypoplasia 7 with Novel Compound Heterozygous Variants of TOE1 in a Boy with Micropenis, Developmental Delay, and Ataxia: The First Korean Case Report.

Pontocerebellar hypoplasia (PCH) is a rare neurodegenerative disorder characterized by hypoplasia of the pons and cerebellum and global developmental delay. Among several PCH types, PCH7 is a characteristic type that manifests with not only brain lesions but also sexual developmental disorders. The causative gene, TOE1, encodes a protein involved in small ribonucleic acid maturation and processing. TOE1 mutation is associated with neuronal survival that causes hypoplasia of the cerebellum and pons. We report the case of a male patient with PCH7, developmental delay, ataxia, micropenis, and undescended testis. Genetic analysis revealed compound heterozygous missense variants (c.955C>T and c.533T>G) in the TOE1 gene.

Adult height in girls with central precocious puberty without gonadotropin-releasing hormone agonist treatment: a retrospective case-control study.

BACKGROUND: The primary aim of this study was to investigate the final adult height (FAH) of girls diagnosed with central precocious puberty (CPP) who were untreated. METHODS: We retrospectively analyzed the medical records of 36 girls diagnosed with CPP between 8 and 9 years of age who did not receive treatment, and 206 girls diagnosed with CPP within the same age range who received gonadotropin-releasing hormone (GnRH) agonist treatment. Midparental height (MPH), predicted adult height (PAH) obtained using height and bone age (BA) at the time of diagnosis (PAH for BA), and PAH obtained using the Bayley-Pinneau method (PAH by BP) were calculated. Additionally, height at the time of growth completion was compared with the predicted height. RESULTS: The FAHs were 160.71±4.56 cm in the untreated group and 159.31±4.26 cm in the treated group. In the untreated group, the FAH was 0.99±4.50 cm shorter than the MPH but 4.29±3.33 cm and 3.46±3.93 cm greater than the PAH for BA and PAH by BP, respectively. CONCLUSION: In children diagnosed with CPP between 8 and 9 years of age who were untreated, FAH was greater than PAH for BA and PAH by BP at the time of diagnosis, indicating that the prognosis of FAH was not poor. Therefore, for girls diagnosed with CPP, it is recommended to consider various conditions, such as pubertal onset, height at diagnosis, BA, peak luteinizing hormone level, predicted height, and speed of puberty, when deciding whether to administer GnRH agonists.

Effect of moderate to severe atopic dermatitis on the prognosis of egg allergy resolution

BACKGROUND: Few studies have examined the effect of atopic dermatitis (AD) on the resolution of food allergies in Asia, and the predictors of egg allergy resolution are not yet well defined. OBJECTIVE: We evaluated whether AD severity could predict the resolution of egg allergy. METHODS: This retrospective cohort study included infants under 24 months of age diagnosed with IgE-mediated egg white allergy. We included subjects who completed a 60-month follow-up. Open oral food challenges (OFCs) and serologic tests were performed at the time of initial diagnosis and at 36 ± 3 and 60 ± 3 months. RESULTS: We analyzed 68 patients (39 boys and 29 girls). OFCs were performed in 88.2% of the patients. The egg allergy remission rates were 23.5% and 47.1% by 3 and by 5 years of age, respectively. Persistent egg allergy was significantly associated with moderate to severe AD and house dust mite sensitization. Kaplan-Meier curve analysis revealed that patients with moderate to severe AD had higher persistent egg allergy rates than patients with no and mild AD (p = 0.012). Multivariable analysis identified moderate to severe AD as strongly associated with persistent egg allergy (p = 0.001). CONCLUSIONS: In this study, 47.1% of infants had resolved egg white allergies at 60 months. Moderate to severe AD may be a practical and important prognostic factor for persistent egg allergy in clinical settings.

Coffin-Siris Syndrome: Case Series of Three Patients and a Novel ARID2 Variant.

Coffin-Siris syndrome (CSS) is a rare congenital disorder characterized by coarse facial features, intellectual disability or developmental delay, and aplasia or hypoplasia of the tips of the fifth finger and/or toes. Mutations in genes affecting the switch/sucrose non-fermenting ATP-dependent chromatin remodeling complex are reported to cause CSS. Here, we describe three CSS patients. Two girls aged 3 and 2 years old presented with global developmental delay, poor growth, and a dysmorphic face. Whole-exome sequencing (WES) was performed and they were diagnosed with CSS due to heterozygous frameshift variants (c.3443_3444del, p.Lys1148ArgfsTer9 and c.2869_2890del, p.Pro957CysfsTer20) in ARID1B A 2-year-old girl presented with gross motor delay and dysmorphic face. She was diagnosed with CSS due to a novel heterozygous frameshift variant (c.4942_4943del: p.Gln1648GlyfsTer8) in ARID2.

Clinical characteristics and treatment response of chronic spontaneous urticaria according to age: A single-center Korean study.

BACKGROUND: Little information exists regarding the incidence of chronic spontaneous urticaria (CSU) or differences in its characteristics according to age. OBJECTIVE: To evaluate the incidence, clinical characteristics and treatment response of CSU according to age. METHODS: The relevance of gender, age, history of allergic disease, pre-diagnosis duration, and treatment response were retrospectively evaluated in patients diagnosed with CSU at Pusan National University Hospital between 2011 and 2018. RESULTS: A total of 970 patients were included in the study, consisting of 198 children and 772 adults. The CSU incidence increased during the study period in children, but not in adults. CSU was more common in adults than in children and the peak age of occurrence was 20-59 years. Increased female incidence was noted in adults, whereas patient and family allergic history was frequently observed in children than in adults. The overall rate of improvement was remarkably higher in children than in adults (P < 0.01), with pre-diagnosis duration and treatment duration both shorter in children than in adults. (P = 0.001). The proportion of men was higher and treatment duration was shorter in adolescence than in the other age groups, whereas the treatment duration was shorter in patients greater or equal to 60 years than in adults under 60 years, and the step 1 treatment rate was higher. CONCLUSIONS: CSU incidence increased annually in children, but not in adults. The clinical characteristics and treatment response of CSU may differ depending on age and clinicians should be made aware of this fact.

Pediatric and Parents' Attitudes Towards COVID-19 Vaccines and Intention to Vaccinate for Children.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination is necessary to reach herd immunity and essential for mitigating the spread of the pandemic. In May 2021, the US FDA and the EU have expanded the emergency use authorization for a COVID-19 vaccine to children aged 12 to 15. The aim of this study was to investigate parental acceptability of COVID-19 vaccination for their children, factors affecting their acceptability, and children's perceptions of COVID-19 vaccines in Republic of Korea. METHODS: We conducted a questionnaire survey at two tertiary hospitals from May 25, 2021 to June 3, 2021. Subjects were parents having children under 18 years and children aged 10-18 years. RESULTS: Two hundred twenty-six parents and 117 children aged 10-18 years were included in the final analysis. Overall, 76.5% and 64.2% of parents intended to get vaccinated against COVID-19 and intended to have their children vaccinated, respectively. However, only 49.6% of children responded that they would get COVID-19 vaccination. In the multivariate analysis, high confidence in the safety of COVID-19 vaccines (adjusted odds ratio [AOR], 4.87; 95% confidence interval [CI], 1.32-24.12), parents' willingness to vaccinate themselves (AOR, 19.42; 95% CI, 6.85-64.00), and awareness of the need to vaccinate children against COVID-19 (AOR, 13.15; 95% CI, 4.77-41.27) were associated with positive factors intention to vaccinate their children. CONCLUSION: This study provides insight into how parents think about the COVID-19 vaccine for their children in South Korea. Our findings could be referenced in establishing a policy for childhood COVID-19 vaccination in the future.

A Case Report for Severe COVID-19 in a 9-Year-Old Child Treated with Remdesivir and Dexamethasone.

Coronavirus disease 2019 (COVID-19) is generally milder in children than in adults, and a substantial proportion of children with the disease have asymptomatic infections. Remdesivir is recommended for severe COVID-19. To date, there are little data on the outcomes of remdesivir treatment in children. We report a case of severe COVID-19 in a previously healthy but obese (body mass index, 27.6; 99.8th percentile of the age) 9-year-old boy treated with remdesivir and dexamethasone. The patient had pneumonia at the time of diagnosis and required supplemental oxygen due to hypoxia one day after diagnosis. The patient developed respiratory distress as his pneumonia progressed rapidly. Therefore, remdesivir with dexamethasone therapy was initiated on hospital day 2. Supplemental oxygen was gradually weaned on hospital day 6 and stopped on hospital day 9. Significant improvement in pneumonic consolidations on chest X-ray was noted on hospital day 8. The patient was discharged on hospital day 21. We did not observe any adverse effects of remdesivir therapy and successfully treated a 9-year-old child with severe COVID-19.