Purchase this article with an account.
Kirk Stephenson, Adrian Dockery, Andrew Green, Jane G Farrar, David J Keegan; Fibrillin 1-associated Autosomal Dominant Non-Marfan Ectopia Lentis with Retinal Detachment. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2789.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To describe the phenotype of a large pedigree with a confirmed Fibrillin 1 (FBN1) mutation (C639Y), exhibiting autosomal dominant ectopia lentis (EL) with rhegmatogenous retinal detachments (RRD), but no systemic manifestations of Marfan syndrome.
As part of the Irish national inherited retinal disease registry, the proband was identified and pedigree mapping was performed. Each family member underwent full history and ophthalmic examination with retinal imaging and next generation sequencing.
Four affected family members were included in the study. A thorough pedigree was mapped, in which evidence of EL was demonstrated in 16 individuals spanning four generations. All four patients had bilateral EL; all were treated with pars plana vitrectomy (PPV) and lensectomy with secondary iris-fixated intraocular lens (IOL) implantation. Five of eight eyes had previously been treated for RRD, four following PPV and lensectomy (by four separate vitreoretinal surgeons) and one spontaneously on a surgically naïve eye. One patient had bilateral RRD. A causative heterozygous mutation was detected in this pedigree in FBN1 (C639Y), which, to our knowledge, has not been described in systemic fibrillinopathy phenotypes (e.g. Marfan syndrome).
Autosomal dominant FBN1 mutations are responsible for a diverse phenotypic spectrum all linked by deranged development and progressive degeneration of connective tissue (fibrillinopathies). There are >800 described pathogenic FBN1 mutations, which may be limited to individual pedigrees.Associated phenotypes vary in tissue specificity, and may present with an array of systemic features e.g. Marfan syndrome (tall stature, hypermobility, cardiac valvular, and EL), Weill-Marchesani syndrome (short stature, glaucoma, EL) or, like this series, be localized to ocular findings (Ectopia Lentis Syndrome, ELS). Distinguishing the phenotype associated with this specific FBN1 mutation from systemic Marfan syndrome is relevant to those affected. The ocular features (EL & RRD) have an effective surgical treatment (PPV/lensectomy/lens implantation), which has allowed visual function to be preserved. The fortunate lack of cardiac features has had a positive impact on this family’s ability to make informed life choices (e.g. health insurance, family planning, travel considerations, occupation, etc.) as well as reassuring them regarding long term prognosis.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only