Connexion

GENATLAS PHENOTYPE

last update : 09-01-2018

Symbol	MFS1
Location	15q21.1
Name	Marfan syndrome 1
Corresponding gene	FBN1
Other symbol(s)	MFS
Main clinical features	characterized by disproportionate tall stature with long bone overgrowth (dolichostenomelia), arachnodactyly, scoliosis, pectus deformities, bilateral ectopia lentis, aortic dilatation or dissection, dural ectasia including the severe neonatal sporadic form with crumpled ears, flexion contractures, pulmonary emphysema and loose skin leading to a senile appearance and a fetal outcome by congenital heart failure within the first year of life
Genetic determination	autosomal dominant
Related entries	. including isolated cases of thoracic aortic aneurysm and Marfan-like syndrome (MASS, OMIM 604308 )
Function/system disorder	connective tissue
	cardiovascular
	eye
Type	disease

Mechanism(s)

Gene mutation	Effect	Comments

missense		affecting either the conserved cysteine residues or residues of the calcium(cb) binding consensus sequence of the cbEGF motifs
deletion	haploinsufficiency	deletions affecting the putative regulatory and promoter region, abolishing transcription of the deleted allele with complete loss of function of one allele, i.e. true haploinsufficiency

Remark(s)

homozygous R485C mutation in consanguineous family with healthy parents and mild phenotype (mimicking autosomal recessive form)

FBN1 mutation is associated with an increased risk for aortic dilatation and dissection whatever the clinical presentation

novel pseudoexon mutation in FBN1, in association with a clinical

diagnosis of MFS1 (Ko 2008)

Genotype/Phenotype correlations

hot spot for neonatal Marfan syndrome in exons 24-27 and 31-32

clustering of mutations in exons 59-65 in milder forms also premature termination codons (PTC) mutations with more common large-joint hypermobility, but less common lens dislocation and retinal detachment

multi-exon out of frame deletion of the FBN1 gene leading to a severe juvenile onset cardiovascular phenotype in Marfan syndrome (Singh 2007)

higher probability of ectopia lentis was found for patients with a missense mutation substituting or producing a cysteine, when compared with other missense mutations

premature termination codon had a more severe skeletal and skin phenotype than did patients with an inframe mutation

exon 24-32 mutations define a high-risk group for cardiac manifestations associated with severe prognosis at all ages

patients with an in-frame mutation within exons 24-32 , have a significantly higher probability of developing ectopia lentis and mitral insufficiency (Faivre 2009)

higher probability of neonatal presentations associated with exon 25 mutations, as well as a higher probability of cardiovascular manifestations (Faivre 2009)