Background: Biallelic defects in the EFEMP2 gene (also referred to as FBLN4), which encodes the extracellular matrix protein FBLN4, are associated with Autosomal Recessive Cutis Laxa type 1B (ARCL 1B) and severe vascular abnormalities, and in particular aortic aneurysms, vascular tortuosity and arterial stenosis.
Aim: To report on a patient with Coarctation of the aorta, aortic aneurysm, arterial tortuosity and no apparent skin disorder, and to present radiological and molecular findings that facilitated the diagnosis.
Methods: Whole exome sequencing (WES) was performed in a 5-months-old female infant of Kurdish descent, who was referred for evaluation and treatment due to Coarctation of the aorta, aortic aneurysm and arterial tortuosity. Due to parental consanguinity the analysis focused on an autosomal recessive mode of inheritance. Sanger sequencing was used to validate suspected variants.
Results: We identified an autosomal recessive c.835C>T missense mutation (NM_016938) in EFEMP2 gene that was previously described only in a compound heterozygous state as causing aortic and pulmonary tortuosity and aneurysms. The mutation was determined to be deleterious by multiple prediction models.
Conclusions: Arterial tortuosity should raise a suspicion for an inherited connective tissue disorder. Mutations in the EFEMP2 gene can cause severe vascular abnormalities, including Coarctation of the aorta and should be considered even in the absence of Cutis Laxa.
