Expectoration of bronchial casts in association with Ramipril treatment.

We report of a 26-year-old female patient who was referred to our centre with congestive heart failure (CHF). Acute myocarditis with a high Parvovirus B19 virus load was diagnosed by myocardial biopsy. CHF improved after start of ramipril 5 mg/d, metoprolol, diuretics, immunoglobins, and a 24-hour infusion of levosimendan. Soon after initiation of medical therapy, the patient started to expectorate bronchial casts with varying frequencies (three times per week to five times daily). Thorough pneumological workup, including histology of the casts, microbiology, and a CT scan of the lungs, did not reveal any cause for bronchial cast formation. Inhalative corticoids were started without any benefit. Two years later, cardiac catheterisation demonstrated normalised left ventricular function. LV end-diastolic pressure, however, was still elevated at 14 mmHg. Endomyocardial biopsies at this time were negative for virus genome. Finally, we changed afterload reduction therapy from ramipril to candesartan. Within 24 hours, expectoration of bronchial casts terminated. Four weeks later, re-exposition to ramipril prompted immediate re-appearance of cast formation, which again stopped with switching back to candesartan. Finally, we were to prove that treatment with ramipril resulted in bronchial cast formation in this patient.

FOXG1 syndrome: genotype-phenotype association in 83 patients with FOXG1 variants.

PurposeThe study aimed at widening the clinical and genetic spectrum and assessing genotype-phenotype associations in FOXG1 syndrome due to FOXG1 variants.MethodsWe compiled 30 new and 53 reported patients with a heterozygous pathogenic or likely pathogenic variant in FOXG1. We grouped patients according to type and location of the variant. Statistical analysis of molecular and clinical data was performed using Fisher's exact test and a nonparametric multivariate test.ResultsAmong the 30 new patients, we identified 19 novel FOXG1 variants. Among the total group of 83 patients, there were 54 variants: 20 frameshift (37%), 17 missense (31%), 15 nonsense (28%), and 2 in-frame variants (4%). Frameshift and nonsense variants are distributed over all FOXG1 protein domains; missense variants cluster within the conserved forkhead domain. We found a higher phenotypic variability than previously described. Genotype-phenotype association revealed significant differences in psychomotor development and neurological features between FOXG1 genotype groups. More severe phenotypes were associated with truncating FOXG1 variants in the N-terminal domain and the forkhead domain (except conserved site 1) and milder phenotypes with missense variants in the forkhead conserved site 1.ConclusionsThese data may serve for improved interpretation of new FOXG1 sequence variants and well-founded genetic counseling.