Sir,
We read with interest the recent article of Shen et al,1 who report a unique Chinese pedigree with the features of ectopia lentis and varicose great saphenous vein. Marfan's syndrome (MFS), clinically diagnosed by characteristic multiple-system abnormalities, lies at one end of a phenotypic spectrum. At the other end of that spectrum are members of the general population who have one feature common to those with MFS.2 Of those patients who fulfil the modified Ghent criteria for full MFS, up to 97% are found to have FBN1 mutations.3 However, the patients presented by Shen et al are atypical. An alternative approach would be to try to postulate an all-encompassing molecular diagnosis that best fits the clinical signs. Venous varicosity is usually secondary to valvular incompetence, a condition that has been strongly associated with heterozygous mutations in the FOXC2 gene on chromosome 16.4 Similarly, a range of anterior segment phenotypes have been described, with mutations in FOXC2 inherited in a dominant manner.5 When aiming for a genetic diagnosis in this family, we would therefore advocate including FOXC2 in the screening set of genes. If a FOXC2 mutation were found in this family, this would represent an interesting extension to the associated phenotype.
References
Shen W, Fu Q, Sui R, Wu J, Liu L . Unique phenotype in a Chinese family pedigree: ectopia lentis with varicose great saphenous vein. Eye 2010; 24 (10): 1614–1617.
Pyeritz RE . The Marfan syndrome. Annu Rev Med 2000; 51: 481–510.
Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet 2010; 47 (7): 476–485.
Mellor RH, Brice G, Stanton AW, French J, Smith A, Jeffery S et al. Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb. Circulation 2007; 115 (14): 1912–1920.
Smith RS, Zabaleta A, Kume T, Savinova OV, Kidson SH, Martin JE et al. Haploinsufficiency of the transcription factors FOXC1 and FOXC2 results in aberrant ocular development. Hum Mol Genet 2000; 9 (7): 1021–1032.
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Khan, K., Ali, M. & Inglehearn, C. A possible genetic answer to a recently reported novel phenotype. Eye 25, 529 (2011). https://doi.org/10.1038/eye.2010.212
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DOI: https://doi.org/10.1038/eye.2010.212
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