Ectopia lentis

Isolated ectopia lentis (EL) is genetically heterogeneous. In autosomal dominant ectopia lentis (ECTOL1), pathogenic variants in the FBN1 gene can be detected in 71-100% of cases. According to the Ghent nosology of 2010, 46% of patients with ectopia lentis and FBN1 variants were retrospectively diagnosed with Marfan syndrome on the basis of additional skeletal or cardiovascular involvement. Since the majority of FBN1 variants identified in patients with EL also occur in patients with aortic dilatation/dissection, EL caused by FBN1 variants should be considered part of the Marfan spectrum.

Isolated recessive ectopia lentis (ECTOL2) is caused by homozygous or combined heterozygous variants in the ADAMTSL4 gene. In sporadic cases with isolated ectopia lentis with no indication of the mode of inheritance, variants in the FBN1 gene were detected in 64% and variants in the ADAMTSL4 gene in 18%. The detection rate of ADAMTSL4 variants in different populations varies greatly between 0% in the Chinese population and 50% in different patient groups of European origin. Homozygous variants in the LTBP2 gene have been identified in individual families with an autosomal recessive syndrome with megalocornea, microspherophakia, progressive ectopia lentis, myopia and secondary glaucoma.

References
Rødahl in: Pagon RA, Adam MP, Ardinger HH, et al. (eds). GeneReviews® (Last Update: July 5, 2018) / Overwater et al. 2017, Eur J Med Genet 60:465 / Chandra et al., Clin Genet 87:284 (2015) / Li et al. 2014, Mol Vis 20:1017 / Chandra et al. 2012, Invest Ophthalmol Vis Sci 53:4889 / Aragon-Martin et al. 2010, Hum Mutat 31:E1622 / Desir et al. 2010, Eur J Hum Genet 18:761