A Rare Case of Autosomal Recessive Cutis Laxa Type Ib in a Young Girl with Arterial Aneurysms and Successful Valve Sparing Root and Aortic Arch Replacement

Background: Autosomal recessive cutis laxa type Ib is a rare and often perinatally lethal syndrome caused by mutations in the EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) gene, leading to a reduced secretion of fibulin-4 which is essential for elastogenesis within cross-linking of collagen and elastin. This loss-off function mechanism leads to reduced and disrupted elastic fibers with extreme tortuosity and fusiform dilatations of nearly all large and medium sized arteries and veins. We describe the case of a 15-year-old girl from a consanguine family with a diagnosis of a giant ascending aortic aneurysm (45 mm) at 1 year of age when a Yacoub's valve sparing root replacement (VSRR) was performed. She presented 14 years later with marked left ventricular hypertrophy, a stenotic aortic conduit and anteposition of her significantly tortuoused head and neck arteries. The succeeding aortic arch was severely dilated (40 mm). Remarkably, her brother died suddenly in infancy with postmortem diagnosis of a giant ascending aneurysm and aortic coarctation.

Method: We performed MRI and CT scans for visualization of the complete arterial and venous system including the former reimplanted coronary arteries during Yacoub's operation. Whole-exome sequencing (WES) was performed and the detected variants were screened in family members including autopsies’ material from the deceased brother.

Results: WES revealed a hitherto unknown homozygous mutation in the EFEMP2 gene (c.905A > G) leading to a missense mutation in exon 9 (p.Asn302Ser) at a location for essential disulfide bonding for correct fibulin-4 structure. Further, a variant of unknown significance (VUR) in COX2 could be detected in the mitochondrial genome. The deceased brother showed both mutations identically, the parents were heterozygous for the EFEMP2 mutation and the mother additionally expressed the mitochondrial VUR. After thorough planning, a redo VSRR with extension into the aortic arch was performed. Postoperative CT proved excellent outcome, surgery was uneventful, and the patient was discharged 10 days postoperatively.

Conclusion: Extensive genetic investigations clarified the unknown cause of the partially lethal connective tissue disorder in this family and with this knowledge a successful redo corrective ascending and aortic arch replacement was performed.

Publication History

Article published online:
12 February 2022