PURPOSE: To describe the genotype-phenotype relationship of a cohort of 
consecutive patients with isolated ectopia lentis (EL) secondary to ADAMTSL4 and 
FBN1 mutations.
METHODS: Patients underwent detailed ocular, cardiovascular, and skeletal 
examination. This was correlated with Sanger sequencing of ADAMTSL4 and FBN1 
genes.
RESULTS: Seventeen patients were examined, including one with ectopia lentis et 
pupillae. Echocardiography and skeletal examination revealed no sign of systemic 
disorders associated with EL, in particular Marfan syndrome (MFS). Nine patients 
(52.9%) were found to have mutations in ADAMTSL4, including four novel nonsense 
mutations. Four patients (25%) were found to have novel FBN1 mutations, not 
previously reported as causing classical Marfan syndrome. One additional patient 
was found to have an FBN1 mutation previously reported in classical MFS. Four 
patients (25%) were found to have no mutations in either gene. Median age of 
diagnosis of EL was 35 years in patients with FBN1 mutations and 2 years in 
patients with ADAMTSL4 mutations (P < 0.01). Mean axial length was 22.74 mm (95% 
confidence interval [CI]: 21.3-24.2) (FBN1) and 27.54 mm (95% CI: 24.2-30.9) 
(ADAMTSL4) (P < 0.01). Other ophthalmic features, including corneal thickness 
and power, foveal thickness, visual acuity, and direction of lens displacement, 
were similar for both groups.
CONCLUSIONS: ADAMTSL4 is the most important known causative gene in isolated EL. 
Mutations in ADAMTSL4 appear to cause earlier manifestation of EL and are 
associated with increased axial length as compared to FBN1. We suggest that 
ADAMTSL4 be screened in all patients with isolated EL and that physicians be 
vigilant for the more severe ocular phenotype associated with mutations in this 
gene.