Early diagnosis enabling precision medicine treatment in a young boy with PIK3R1-related overgrowth.

Mosaic PIK3R1 variants have recently been demonstrated in patients with complex vascular malformations and overgrowth in a syndrome resembling PIK3CA-related overgrowth syndrome (PROS). The PIK3CA-inhibitor, alpelisib, seems to be a promising treatment option for PROS patients. We describe a young boy with overgrowth and a pathogenic mosaic variant in PIK3R1; c.1699A > G, p.(Lys567Glu). He was prenatally suspected of a syndrome on the presence of unusual transient fluctuating subcutaneous edemas and lymphedema of his left shoulder. The pathogenic variant, later found to be causative, was below detection threshold in whole-genome sequencing (WGS) analysis of amniotic fluid. Upon delivery a mosaic pathogenic PIK3R1 variant, was identified by whole-exome sequencing (WES) of a skin biopsy. With no proven treatment options available, and based on the theoretical disease mechanism, alpelisib therapy was initiated at nine months of age. In the first year of treatment growth normalized and the affected vascular and lymphatic tissue regressed. No side effects have been observed. This report underlines the importance of early variant detection in children suspected of having severe mosaic overgrowth, and proves that prenatal diagnosis is possible, enabling prompt treatment. Furthermore, it demonstrates the promising effects of alpelisib in this patient group.

Children Hospitalized With Varicella in Denmark: Sensitivity of the National Patient Register.

BACKGROUND: Varicella, common in childhood and most often self-limiting, may cause complications including bacterial superinfection, pneumonia and encephalitis. Universal childhood varicella vaccination has been introduced in several countries, but is controversial in Europe. In Denmark, varicella is not part of the national immunization program and there is no national surveillance of varicella. The primary aim of the study was to describe the epidemiology and clinical characteristics of children hospitalized with varicella in Denmark. The secondary aim was to validate the sensitivity and completeness of the Danish National Patient Register. METHODS: Active surveillance of children hospitalized with varicella was carried out at 4 pediatric departments. In the Danish National Patient Register, we identified all children discharged with an International Classification of Diseases, 10th revision code of varicella from the 4 departments. We used a capture-recapture analysis to estimate the "true" number of hospitalized children with varicella. RESULTS: By active surveillance, we identified 86 children eligible for clinical description. In 87% of cases, the children were 0-4 years of age. Complications were identified in 69% of patients, including 1 child with postvaricella cerebral angiopathy. In the National Patient register (NPR), we identified 125 children with a discharge diagnosis of varicella. By capture-recapture analysis, the sensitivity of the NPR was estimated to be 74%. CONCLUSIONS: Varicella can cause serious complications including cerebral angiopathy in children in Denmark. The NPR will be a useful tool for estimating hospitalization incidence, but will underestimate the true number of hospitalizations.

[Post-exposure prophylaxis against measles]. / Posteksponeringsprofylakse mod mæslinger.

This review article deals with the newest guidelines in post-exposure prophylaxis against measles and puts forward recommendations on how this prophylaxis should be handled with regards to children in all ages, both immunosuppressed and competent.

[Chronic HBV infection in a two year-old girl in spite of correct HBV vaccination after birth]. / Kronisk HBV-infektion hos en toårig pige trods korrekt HBV-vaccination efter fødslen.

Our case story is about a two year-old girl who, despite full vaccination with neonatal hepatitis B immunoglobulin and hepatitis B vaccination and revaccination with hepatitis B vaccine at one, two and 12 months of age, got chronic hepatitis B presumably due to intrauterine mother-to-child transmission. Her mother was known to be HBsAg and HBeAg positive with genotype C and a viral load of one billion IU/ml. It is important that children with HBV infection are detected and seen in a special department. Post-vaccination screening of children from HBsAg positive mothers should be considered.

Influenza-associated illness is an important contributor to febrile convulsions in Danish children.

OBJECTIVE: To determine the burden of febrile convulsions attributed to influenza like illness in a western country during ten influenza seasons. METHODS: Based on national Danish registries, we explored the association between influenza like illness (ILI) activity and weekly number of hospital admittances for febrile convulsions in time-series analyses. We included data on 59,870 admissions for febrile convulsions in children between three months and five years of age in the period 1995-2005. RESULTS: There was a significant relation between ILI-activity and number of children admitted for febrile convulsions with a systematic increase in admissions to pediatric wards about one week before the national surveillance system detected the corresponding rise in ILI-activity. The yearly number of admissions attributable to ILI varied from 11 to 47% of admissions and was highest during influenza epidemics. This was in particular observed in seasons when a new strain of influenza A/H3N2 was circulating. During these epidemics, influenza contributed to 29-47% of admissions. CONCLUSIONS: Influenza like illness is associated with a considerable burden of febrile convulsions in children, most pronounced in years with epidemics. As febrile convulsions are just one of many complications contributing to the burden of influenza in children, this should be taken into consideration when planning a vaccination strategy for preventing influenza-related morbidity in younger children.

Universal screening for hepatitis B among pregnant women led to 96% vaccination coverage among newborns of HBsAg positive mothers in Denmark.

In Denmark selective screening programs of pregnant women for hepatitis B missed 30-50% of high-risk groups and in late 2005 a universal screening of pregnant women for HBsAg was implemented. During a 2-year period a prospective enhanced surveillance of the universal screening was performed to examine the effectiveness of universal HBV-screening of pregnant women and HBV-immunizations of their newborn, and to provide a prevalence-estimate for HBV in Denmark. On a opt out basis all women in Denmark attending antenatal care were tested for hepatitis B serology. Vaccination data of the newborns and households of HBsAg positive pregnant women were assembled. Among 140,376 HBsAg tests of pregnant women, 371 (0.26%) were positive. The prevalence among women of Danish origin was 0.012% and 2.74% among foreign born women, highest for women from Southeast Asia (14.5%). Genotype C was the most prevalent (37%) and 13% had a HBVDNA ≥10(8) IU/ml. The prevalence estimate of chronic hepatitis B in Denmark was 0.2-0.3% in the general population. Among children born within the project period, 96% received vaccination at birth compared to 50% of siblings born prior to universal screening. During 3 years of passive follow-up two transmissions (0.5%) have been notified. Among children born of the positive mothers prior to the trial-period 7.3% had been notified. Thus the prevalence of HBV positive mothers has more than doubled in Denmark over the last 40 years, but among women of Danish origin it has decreased 10-fold. By replacing selective screening with universal, identification of newborns in need of HBV-immunization was increased from 50% to almost complete coverage, and also identifies mothers with high viral load for evaluation of pre-term treatment to interrupt in utero transmission.

Burden of illness of the 2009 pandemic of influenza A (H1N1) in Denmark.

We analysed Danish surveillance data to estimate influenza-associated morbidity and mortality in 2009. To obtain population-based estimates of the clinical attack rate, we combined data from two different primary health care surveillance systems, national numbers of the proportion of positive influenza tests, and data from a web-based interview on health care seeking behaviour during the pandemic. From a national registry, we obtained data on hospital admissions (ICD-10 codes) for influenza related conditions. Admission to intensive care was monitored by a dedicated surveillance scheme. Mortality was estimated among laboratory confirmed cases but was also expressed as excess all-cause mortality attributed to influenza-like illness in a multivariable time series analysis. In total, we estimated that 274,000 individuals (5%) in Denmark experienced clinical illness. The highest attack rate was found in children 5-14 years (15%). Compared with the expected number of hospital admissions, there was an 80% increase in number of influenza related hospital admissions in this age group. The numbers of patients admitted to intensive care approached 5% of the national capacity. Estimates of the number of deaths ranged from 30 to 312 (0.5-5.7 per 100,000 population) depending on the methodology. In conclusion, the pandemic was characterised by high morbidity and unprecedented high rates of admissions to hospitals for a range of influenza-related conditions affecting mainly children. Nonetheless, the burden of illness was lower than assumed in planning scenarios, and the present pandemic compares favourable with the 20th century pandemics.