Brugada syndrome (BrS) is a rare inherited arrhythmia syndrome. Affected children may experience life-threatening symptoms, mainly during fever. The percentage of SCN5A variant carriers in children... Show moreBrugada syndrome (BrS) is a rare inherited arrhythmia syndrome. Affected children may experience life-threatening symptoms, mainly during fever. The percentage of SCN5A variant carriers in children is higher than in adults. Current diagnostic and follow-up policies for children with (a family history of) BrS vary between centres. Here, we present a consensus statement based on the current literature and expert opinions to standardise the approach for all children with BrS and those from BrS families in the Netherlands. In summary, BrS is diagnosed in patients with a spontaneous type 1 electrocardiogram (ECG) pattern or with a Shanghai score >= 3.5 including >= 1 ECG finding. A sodium channel-blocking drug challenge test should only be performed after puberty with a few exceptions. A fever ECG is indicated in children with suspected BrS, in children with a first-degree family member with definite or possible BrS according to the Shanghai criteria with a SCN5A variant and in paediatric SCN5A variant carriers. In-hospital rhythm monitoring during fever is indicated in patients with an existing type 1 ECG pattern and in those who develop such a pattern. Genetic testing should be restricted to SCN5A. Children with BrS and children who carry an SCN5A variant should avoid medication listed at and fever should be suppressed. Ventricular arrhythmias or electrical storms should be treated with isoproterenol infusion. Show less
Borras, D.M.; Vossen, R.H.A.M.; Liem, M.; Buermans, H.P.J.; Dauwerse, H.; Heusden, D. van; ... ; Anvar, S.Y. 2017
Predicting the likelihood that an individual is a BRCA mutation carrier is the first step to genetic counseling, followed by germ-line mutation testing in many family cancer clinics. Individuals... Show morePredicting the likelihood that an individual is a BRCA mutation carrier is the first step to genetic counseling, followed by germ-line mutation testing in many family cancer clinics. Individuals who have been diagnosed as BRCA mutation-positive are offered special medical care; however, clinical management in the case of a negative test result or an unclassified variant in BRCA1 or BRCA2 can be difficult. Since it is estimated that 15% of BRCA mutation carriers are missed by current diagnostics and assessment of the clinical significance of many unclassified variants is complex and time consuming, new strategies are emerging that are able to predict BRCA dysfunction based on molecular tumor information (BRCAness) rather than on family history. This thesis starts with reviewing the importance of BRCA status assessment, followed by the studies performed by SA Joosse in which array comparative genomic hybridization has been utilized for the prediction of the involvement of BRCA in tumorigenesis. Show less
