Inherited cavernous malformations of the central nervous system: clinical and genetic features in 19 Swiss families

Cavernous malformations (CCMs) are benign, well-circumscribed, and mulberry-like vascular malformations that may be found in the central nervous system in up to 0.5% of the population. Cavernous malformations can be sporadic or inherited. The common symptoms are epilepsy, hemorrhages, focal neurological deficits, and headaches. However, CCMs are often asymptomatic. The familiar form is associated with three gene loci, namely 7q21-q22 (CCM1), 7p13-p15 (CCM2), and 3q25.2-q27 (CCM3) and is inherited as an autosomal dominant trait with incomplete penetrance. The CCM genes are identified as Krit 1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3). Here, we present the clinical and genetic features of CCMs in 19 Swiss families. Furthermore, surgical aspects in such families are also discussed.

Management of phenylketonuria in Europe: survey results from 19 countries

To gain better insight in the most current diagnosis and treatment practices for phenylketonuria (PKU) from a broad group of experts, a European PKU survey was performed. The questionnaire, consisting of 33 questions, was sent to 243 PKU professionals in 165 PKU centers in 23 European countries. The responses were compiled and descriptive analyses were performed. One hundred and one questionnaires were returned by 93/165 centers (56%) from 19/23 European countries (83%). The majority of respondents (77%) managed patients of all age groups and more than 90% of PKU teams included physicians or dieticians/nutritionists. The greatest variability existed especially in the definition of PKU phenotypes, therapeutic blood phenylalanine (Phe) target concentrations, and follow-up practices for PKU patients. The tetrahydrobiopterin (BH4; sapropterin) loading test was performed by 54% of respondents, of which 61% applied a single dose test (20mg/kg over 24h). BH4 was reported as a treatment option by 34%. This survey documents differences in diagnostic and treatment practices for PKU patients in European centers. In particular, recommendations for the treatment decision varied greatly between different European countries. There is an urgent need to pool long-term data in PKU registries in order to generate an evidence-based international guideline.