Early-Onset Marfan Syndrome: A Case Series

Abstract

Mutations in fibrillin 1 cause Marfan syndrome (MFS), an autosomal dominant disorder of the connective tissue, with multisystem manifestations. In early-onset MFS, the physical characteristics are expressed much earlier than the classical MFS. Those affected by this form generally have their mutations restricted to the gene “hotspot” region of exons 24 to 32. Historically, affected individuals usually die within the first few years of life due to heart failure secondary to severe valvular insufficiency. We report three patients with early-onset MFS, whose clinical evolution has been remarkably positive, when compared with other reported cases in the literature.

Successful Mitral Valve Replacement in an Infant with Neonatal Marfan Syndrome due to a Novel Missense Mutation of the <i>FBN1</i> Gene

“…Although MVR in early infancy is often challenging, recent improvements in surgical techniques and devices have improved its surgical performance. 18) Children with MFS generally exhibit average intellectual and gross motor development. 23) In our patient, neurological development was consistent with that reported in a previous report.…”

“…We found a total of 20 cases that have been reported in 16 studies (Table ). 3,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Various surgical procedures such as mitral valvuloplasty (31%), MVR (26%), mitral annu- loplasty (11%), tricuspid annuloplasty (9%), tricuspid valvuloplasty (9%), tricuspid valve replacement (6%), valvesparing aortic root replacement (3%), Bentall procedure (3%), and repair of mitral chordae tendineae rupture (3%) were performed in these cases. In these cases, 11 (55%) patients were female, and the average age at surgery was 20 months (range, 1 month to 7 years).…”

Subdural Hygroma in an Infant with Marfan's Syndrome

“…8 Indeed, by Hennekam's criteria, our patient had EOMFS rather than neonatal MFS, and his FBN1 point mutation (c.6313_5G > A; extended splice site) is in intron 51 rather than in the region purportedly associated with higher risk for neonatal MFS. 6,8,10 Dural ectasia is reported in 63 to 92% of MFS patients, and unlike other features of classic MFS in adulthood, it is present in 40% of pediatric patients. 5,11 It can lead to cerebrospinal fluid leaks and thereby to spontaneous intracranial hypotension (SIH): subdural fluid collections, most of which are SDHy, are present in 50% of SIH patients (regardless of MFS).…”

“…Mutations of FBN1 in the region between exons 24 and 32 belong to the few generally accepted genotypephenotype correlations of MFS and are associated with neonatal MFS. [8][9][10] Although all reported mutations associated with neonatal MFS are found in that region, mutations associated with EOMFS or classic MFS can be found there as well, rendering it impossible to predict whether a given mutation in exons 24 to 32 will be associated with classic MFS, EOMFS, or neonatal MFS. 8 Indeed, by Hennekam's criteria, our patient had EOMFS rather than neonatal MFS, and his FBN1 point mutation (c.6313_5G > A; extended splice site) is in intron 51 rather than in the region purportedly associated with higher risk for neonatal MFS.…”

Cardiomyopathy in Genetic Aortic Diseases

“…Aortic root dilatation is also commonly present in children with nMFS but does not account for the most significant morbidity and mortality in this age group. Most children with nMFS die within the 1 st year of life of cardiac failure (20), although the number of survivors into teenage years is increasing thanks to improvement in care (23,24).…”