Cervical artery dissection expands the cardiovascular phenotype in FBN1‐related Weill–Marchesani syndrome

Abstract

Weill-Marchesani syndrome (WMS) is a rare form of acromelic dysplasia that is characterized by distinctive skeletal, ocular, and cardiovascular abnormalities. Previously described cardiac manifestations of WMS include aortic and pulmonary valve stenosis, mitral valve prolapse, mitral stenosis, and QTc prolongation. Autosomal dominant forms of WMS result from heterozygous pathogenic variants in FBN1, a gene with a well characterized role in the pathogenesis of thoracic aortic aneurysm (TAA) in the context of Marfan syndrome. In contrast, only one patient has been reported with aortic disease in WMS. Although the risk of aortic dissection from preceding TAA remains the leading cause of morbidity for individuals with Marfan syndrome, rare reports of arterial dissection in the peripheral vasculature have been described. Peripheral artery dissection has not been previously reported in other FBN1-related diseases. We describe a three generation family with FBN1-related WMS whose cardiovascular manifestations include TAA and cervical artery dissection, thus expanding the cardiovascular phenotype of WMS. Further research is required to quantify these risks and establish appropriate recommendations for cardiovascular imaging, medical management, and prophylactic surgical intervention in individuals with FBN1--related acromelic dysplasia.

New developments in the genetic diagnosis of short stature

“…It is well known that FBN1 mutations in Marfan syndrome can cause aortic aneurysm or dissection, but it is important to be aware that the heterozygous FBN1 mutations that cause short stature, especially in patients with Weill-Marchesani syndrome 2 and geleophysic dysplasia, also have been associated with various cardiac valve issues or aortic aneurysm [24]. How mutations in the same gene can cause opposite effects on growth but similar cardiac findings remain to be clarified [25]. The distinctive phenotype caused by FBN1 mutations is described in Table 1.…”

Acromelic dysplasias: how rare musculoskeletal disorders reveal biological functions of extracellular matrix proteins

“…(The Marfan syndrome–causing FBN1 mutation is listed in the UMD‐FBN1 database as ID 148 and is unpublished. ) 12,78,112 All SMAD4 mutations associated with Myhre syndrome are gain‐of‐function mutations and affect two amino acid residues located in the SMAD4 MH2 domain.…”

Neural/Bayes network predictor for inheritable cardiac disease pathogenicity and phenotype

“…Cardiovascular phenotype (cp) describes conditions affecting the cardiovascular system but not directly the myocardium (e.g. valvulopaties, aortic coarctation) [16,17]. Congenital myopathy (gm) are muscular diseases of genetic etiology that rarely affects the heart.…”