van Peter Tintelen

Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome

Radonic T, de Witte P, Groenink M, de Bruin‐Bon RACM, Timmermans J, Scholte AJH, van den Berg MP, Baars MJH, van Tintelen JP, Kempers M, Zwinderman AH, Mulder BJM. Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome.

Founder mutations in hypertrophic cardiomyopathy patients in the Netherlands

In this part of a series on cardiogenetic founder mutations in the Netherlands, we review the Dutch founder mutations in hypertrophic cardiomyopathy (HCM) patients. HCM is a common autosomal dominant genetic disease affecting at least one in 500 persons in the general population. Worldwide, most mutations in HCM patients are identified in genes encoding sarcomeric proteins, mainly in the myosin-binding protein C gene (MYBPC3, OMIM #600958) and the beta myosin heavy chain gene (MYH7, OMIM #160760). In the Netherlands, the great majority of mutations occur in the MYBPC3, involving mainly three Dutch founder mutations in the MYBPC3 gene, the c.2373_2374insG, the c.2864_2865delCT and the c.2827C>T mutation. In this review, we describe the genetics of HCM, the genotype-phenotype relation of Dutch founder MYBPC3 gene mutations, the prevalence and the geographic distribution of the Dutch founder mutations, and the consequences for genetic counselling and testing. (Neth Heart J 2010;18:248-54.)

Diagnostic yield in adults screened at the marfan outpatient clinic using the 1996 and 2010 ghent nosologies

Marfan syndrome (MFS) is diagnosed according to the Ghent nosology, which has recently been revised. In the Netherlands, evaluation for possible MFS is performed in specialized Marfan outpatient clinics. We investigated the diagnostic yield in our clinic and the impact of the 2010 nosology. All adult patients (n = 343) who visited our clinic between 1998 and 2008 were included. We analyzed their reasons for referral, characteristics, and established diagnoses. In addition, we applied the 2010 nosology to all patients and compared the outcomes to those obtained with the 1996 nosology. Diagnoses that were made using the 1996 and the 2010 Ghent nosology included MFS (44/343 vs. 47/343), familial thoracic aortic aneurysm and/or dissection (22/343 vs. 22/343 patients), Loeys–Dietz syndrome (4/343 vs. 4/343 patients), and (familial) mitral valve prolapse (MVPS; 5/343 vs. 28/343 patients). In both nosologies, 77% of MFS patients had an FBN1 mutation. The 2010 nosology led to an increase in the number of diagnoses made: 4 additional cases of MFS were identified (one patient was “lost” who no longer fulfilled the criteria) and 23 additional cases of MVPS were diagnosed. The diagnostic yield of patients with aortic root dilatation was 65% using the 1996 nosology and 70% using the 2010 nosology. The change in diagnoses did not lead to a difference in clinical follow‐up. We conclude that the diagnostic yield of our specialized clinic was high, in particular in patients with aortic root dilatation. Further more the 2010 Ghent nosology led to a significant increase in the number of diagnoses made, mainly due to lowering of the diagnostic threshold for MVPS.

Haplotype sharing test maps genes for familial cardiomyopathies

van der Zwaag PA, van Tintelen JP, Gerbens F, Jongbloed JDH, Boven LG, van der Smagt JJ, van der Roest WP, van Langen IM, Bikker H, Hauer RNW, van den Berg MP, Hofstra RMW, te Meerman GJ. Haplotype sharing test maps genes for familial cardiomyopathies.