Employment, occupation, and income in adults with neurofibromatosis 1 in Denmark: a population- and register-based cohort study.

BACKGROUND: Little is known about employment status, occupation, and disposable income in adults with NF1. METHODS: From the Danish National Patient Registry and database of two national Centers for Rare Diseases, we identified 1469 adults with NF1, who were matched to 11,991 randomly selected population comparisons on sex and birth year and month. Annual information on employment, occupation and disposable income was ascertained from national registries in 1980-2019. RESULTS: Adults with NF1 had a lower odds ratio (OR) for employment [OR 0.71, 95% confidence interval (CI) 0.61-0.83] and higher OR for health-related unemployment (OR 2.94, 95% CI 2.16-3.96) at age 30 years than population comparisons, which persisted at age 40 and 50 years. Somatic diagnoses were associated with a higher OR for health-related unemployment in adults with NF1 than in the population comparisons. Adults with NF1 had a slightly lower disposable income, with a 14% (0.82-0.89) reduction observed among the youngest birth cohort. Furthermore, adults with NF1 were less likely to be in a high skilled occupation at ages 30, 40 and 50 years. CONCLUSION: Adults with NF1 have a lower employment rate, which was mainly due to health-related reasons and a slightly lower disposable income than adults without NF1. Thus, anticipation guidance for employment should be part of the management of NF1 families.

Succesful MEK-inhibition of severe hypertrophic cardiomyopathy in RIT1-related Noonan Syndrome.

Infants with Noonan Syndrome and hypertrophic cardiomyopathy have a poor prognosis and a high mortality especially when diagnosed before six months of age. As for the majority of the RASopathies, no medical treatment has been approved for Noonan Syndrome. Meanwhile, several approved agents targeting the same RAS/MAPK signaling pathway are used in cancer treatment. In this case report we describe a child with Noonan Syndrome caused by a pathogenic RIT1 variant, who developed severe early-onset hypertrophic cardiomyopathy and pulmonary valve stenosis. She received off-label treatment with the MEK-inhibitor trametinib which resulted in complete remission of the cardiac hypertrophy and a significant improvement of the pulmonary valve stenosis. Our case emphasizes the potential of existing cancer agents targeting the RAS/MAPK signaling pathway as successful treatment for RASopathy manifestations.

School performance of children with neurofibromatosis 1: a nationwide population-based study.

Children with neurofibromatosis 1 (NF1) may have a high burden of somatic disease and cognitive impairments, which can lead to poor academic performance. We evaluated school grades from exams ending mandatory schooling (usually around age 15 or 16 years) of children with NF1 in a population-based registry study using a within-school matched design. The study included 285 children with NF1 and 12,000 NF1-free peers who graduated from the same school and year during 2002-2015. We estimated overall and gender-specific grades by subject and compared the grades of children with NF1 with those of NF1-free peers in linear regression models. We also examined the effect of social and socioeconomic factors (immigration status and parental education, income and civil status) on grades and age at finalizing ninth grade. School grades varied considerably by socioeconomic stratum for all children; however, children with NF1 had lower grades by an average of 11-12% points in all subjects. In the adjusted models, children with NF1 had significantly lower grades than their NF1-free peers, with largest negative differences in grades observed for girls with NF1. Finally, children with NF1 were 0.2 (CI 0.1-0.2) years older than their peers on graduating from ninth grade, but only maternal educational modified the age at graduating. In conclusion, students with NF1 perform more poorly than their peers in all major school subjects. Gender had a strong effect on the association between NF1 and school grades; however, socioeconomic factors had a similar effect on grades for children with NF1 and their peers.

Central Venous Catheters and Bloodstream Infection During Induction Therapy in Children With Acute Lymphoblastic Leukemia.

The purpose of the study was to assess the risk of first-time bloodstream infection (BSI) according to type of central venous catheter (CVC) during induction therapy in children with acute lymphoblastic leukemia (ALL). Patients eligible for our analysis were all newly diagnosed children with ALL treated at 3 pediatric centers in Denmark between 2008 and 2014. A total of 136 patients were followed from initial CVC placement until first BSI, CVC removal, death, or day 28, whichever occurred first. Thirty-nine BSIs were detected, of which 67% were gram-positive infections, and 59% met the criteria for being CVC associated. The 28-day cumulative incidence of BSI was similar in 77 patients with a nontunneled CVC (28%; 95% confidence interval, 19%-40%) and in 59 patients with a tunneled CVC with external lines (TE) (33%; 95% confidence interval, 23%-47%). Subgroup analyses showed that gram-negative blood isolates occurred more frequently in patients with a TE, and that lower incidences of BSI were detected in patients older than 9 years with a TE, and in patients with T-ALL. It is concluded that the type of CVC inserted at diagnosis has no impact upon the risk of BSI in patients with ALL undergoing induction therapy.