Thymine > cytosine missense mutation at nucleotide 3538 in fibrillin-1 gene in Marfan syndrome: A case report of an aggressive phenotype

Aim: To report the case of a patient with Marfan syndrome that presented with an heterozygous change from thymine (T) to cytosine (C) at nucleotide 3538, resulting in a missense change from cysteine to arginine at codon 1180 in exon 28 (3538 T>C; cys1180arg) of the FBN1 gene, causing a severe phenotype of the disease with earlyonset bilateral lens subluxation with nasal displacement of the lens and absent zonules. Background: Ectopia lentis (EL) is a major criterion to diagnose MFS, a connective tissue disorder caused by a mutation in the FBN1 gene. Case Description: An 11-year-old boy with a history of MFS causing severe aortic root dilatation with increasing dimension and no evidence of dissection. Refraction revealed bilateral myopia with astigmatism and deprivation amblyopia in the left eye. Slit-lamp examination evidenced iridodonesis with flat iris in both eyes, and nasal displacement of the lens that was mild in the right eye and moderate in the left eye with absent temporal zonular ligaments. Conclusion: MFS typically presents with EL with superotemporal displacement of the lens secondary to zonular laxity. Our patient has bilateral lens subluxation with nasal displacement of the lens and absent zonules, due to a missense change from cysteine to arginine at codon 1180 in exon 28 (3538 T>C; cys1180arg) of the FBN1 gene, resulting in a severe phenotype of the disease. Clinical Significance: This mutation can be the cause of an aggressive phenotype with complete zonular weakness at a young age.