Genotype-phenotype Correlation In Fibrillin-1 And ADAMTSL4 Ectopia Lentis

Abstract

Purpose: : To determine if the inheritance pattern, and ocular presentation can differentiate two major genetic subgroups of ectopia lentis (EL).

Methods: : Of 33 non Marfan syndrome EL patients studied, 21 had FBN1 mutations with no cardiac involvement (Ghent negative); 6 had causative ADAMTSL4 mutations; 6 had neither. Clinical notes were reviewed.

Results: : Of the 21 FBN1-mutation patients 19 had bilateral lens dislocation compared to four patients in the ADAMTSL4 group. Lens movement was in no specific direction in either group. Fifteen (71%) of the FBN1 had dominant family history, whilst seven (37%) demonstrated marfanoid build. No FBN1 mutation patients had cataracts compared to three out of six ADAMTSL4 patients. Three out of the six ADAMTSL4 group had an affected sibling, and two had first cousin parents: suggesting recessive inheritance.Of the remaining six patients where no mutations have been found, four out of six demonstrated dominant inheritance, and two had a possible recessive inheritance, suggesting at least two further genes (1 dominant, 1 recessive) causing EL.

Conclusions: : Two major EL subgroups can be distinguished clinically by trends in inheritance pattern, body habitus, bilaterality of disease and incidence of cataract. Further work is required to increase the cohort size and thus identify other genes predicted to cause EL, their possible interactions, and further clarify genotype- phenotype relationships.

Keywords: gene screening • genetics