The new Ghent criteria for Marfan syndrome: what do they change?

Abstract

International audienceThe diagnosis of Marfan syndrome (MFS) is challenging and international criteria have been proposed. The 1996 Ghent criteria were adopted worldwide, but new diagnostic criteria for MFS were released in 2010, giving more weight to aortic root aneurysm and ectopia lentis. We aimed to compare the diagnosis reached by applying this new nosology vs the Ghent nosology in a well-known series of 1009 probands defined by the presence of an FBN1 mutation. A total of 842 patients could be classified as MFS according to the new nosology (83%) as compared to 894 (89%) according to the 1996 Ghent criteria. The remaining 17% would be classified as ectopia lentis syndrome (ELS), mitral valve prolapse syndrome or mitral valve, aorta, skeleton and skin (MASS) syndrome, or potential MFS in patients aged less than 20 years. Taking into account the median age at last follow-up (29 years), the possibility has to be considered that these patients would go on to develop classic MFS with time. Although the number of patients for a given diagnosis differed only slightly, the new nosology led to a different diagnosis in 15% of cases. Indeed, 10% of MFS patients were reclassified as ELS or MASS in the absence of aortic dilatation; conversely, 5% were reclassified as MFS in the presence of aortic dilatation. The nosology is easier to apply because the systemic score is helpful to reach the diagnosis of MFS only in a minority of patients. Diagnostic criteria should be a flexible and dynamic tool so that reclassification of patients with alternative diagnosis is possible, requiring regular clinical and aortic follow-up

Study of phenotype evolution during childhood in Marfan syndrome to improve clinical recognition

“…The succession of classifications (Berlin, Ghent 1, and Ghent 2) illustrates the difficulty in diagnosis. [4][5][6][7] Although the phenotype in adults is becoming well documented, data in children are much rarer because of marked phenotypic variability both between and within families, and incomplete phenotype in the young, limiting effectiveness of familial screening in children in the absence of molecular biology. Therefore, child populations examined in earlier reports were possibly biased toward severe phenotypes.…”

Chest Pain in Children With Suspected Type I Fibrillinopathy: A Case Report

“…15 MVP is considered the most common primary valvular abnormality in young populations (prevalence 2% to 5%), 16,17 and it is often associated with heritable connective tissue disorders. 4,15,18 It is usually a benign asymptomatic condition, although it is also related to a confusing array of seemingly unrelated symptoms of dysautonomia that cannot be explained on the basis of mitral regurgitation alone, such as palpitations, orthostatic hypotension, syncope fatigue-exercise intolerance, chest pain, shortness of breath, and panic attacks, which are collectively called MVP syndrome. 17,18 Moreover, inferior ECG lead abnormalities may occasionally be found, as well as typically early repolarization patterns and ST-segment depression or T-wave inversion, mimicking myocardial ischemia.…”

“…First, because of the evolving nature of some clinical manifestations of Marfan syndrome, classic signs are rarely present in younger children and usually appear as the disease progresses over time. 4 Second, the broad spectrum of type 1 fibrillinopathies, as well as the wide clinical heterogeneity among individuals and families affected with the same mutation, result in a challenging phenotypic-genotypic correlation. 8,9 Furthermore, extensive phenotypic overlapping is observed in the general population, with high prevalence of MVP or skeletal marfanoid disorders 10,11 and so-called MM conditions.…”

“…After 48 hours, ECG abnormalities remained unchanged. The child did not fulfill Ghent-modified criteria for Marfan syndrome, 4 and he was discharged with a diagnosis of thoracic pain secondary to MVP associated with inferior repolarization abnormalities in the context of milder Marfan (MM) phenotype. Genetic testing of the fibrillin 1 gene (FBN1) revealed a heterozygous missense mutation in the proband (c.7605C.G; p.Cys1084Trp), involving Cys residues of calcium-binding epidermal growth factor-like modules.…”

Hereditary Connective Tissue Disorders: Nomenclature and Diagnostic Algorithm

“…До-стоинства и ограничения пересмотренной версии Гент-ских критериев продолжают обсуждаться. Сравнение диагностической ценности новых и старых Гентских критериев у пациентов с подтвержденной мутацией гена FBN1 показало их сопоставимость [10]. Вместе с тем возможна гиподиагностика патологии из-за недо-оценки значения эктазии твердой мозговой оболочки и дилатации аорты у пациентов с высоким показателем площади поверхности тела [11].…”