Is ectopia lentis in some cases a mild phenotypic expression of Marfan syndrome? Need for a long-term follow-up.
OBJECTIVE
Ectopia lentis (EL) and Marfan syndrome (MFS) are considered two distinct clinical entities. We performed genetic and clinical studies to investigate whether EL is actually distinct from MFS or if it is a mild phenotypic expression of it.


METHODS
Seven patients with EL were followed for 5-10 years. Mutation screening analysis of the 65 exons of FBN1 was performed by polymerase chain reaction (PCR) amplification of genomic DNA, denaturing high pressure liquid chromatography analysis, and direct sequencing of heteroduplexes.


RESULTS
Yearly examinations during the 10 years of follow-up allowed the detection of a late onset of dural ectasia in six out of seven patients (age range: 32-64 years versus 8-55 years in MFS previously reported). We also detected the onset of mild thoracic aortic dilatation in a sporadic case (age 45). Six out of seven index cases of EL turned out to be mild forms of Marfan syndrome with possible late cardiovascular involvement as detected in one case. Four novel missense mutations and one known splicing mutation were detected in five out of seven (71%) patients. Their localization confirmed the presence of a first hot spot within exons 1-15 and suggested the presence of a second one between exons 31-39.


CONCLUSIONS
The presence of a second major criterion in six EL patients shifted the clinical diagnosis from EL to MFS. These data demonstrate that some cases, which are initially diagnosed as EL, turn out to be mild Marfan patients. A clinical cardiovascular follow-up is therefore highly recommended for all EL patients since they may develop thoracic aortic aneurysm (TAA) or dissection later in life. Also magnetic resonance imaging (MRI) for dural ectasia (DE) should be performed in a complete follow up for a MFS diagnosis.
Pepe
Guglielmina
G
Department of Medical and Surgical Critical Care, University of Florence, Regional Marfan Centre, Florence, Centre of Research, Transfer, High Education 'DENOTHE', University of Florence, Italy. g.pepe@dac.unifi.it
Lapini
Ilaria
I
Evangelisti
Lucia
L
Attanasio
Monica
M
Giusti
Betti
B
Lucarini
Laura
L
Fattori
Rossella
R
Pellicanò
Giannantonio
G
Scrivanti
Mario
M
Porciani
Maria Cristina
MC
Abbate
Rosanna
R
Gensini
Gian Franco
GF
D000293:Adolescent; D000328:Adult; D002648:Child; D004479:Ectopia Lentis / Q000150:complications* / Q000235:genetics; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000150:complications*; D008840:Microfilament Proteins / Q000235:genetics; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D013997:Time Factors; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines