Valve-Sparing Root and Total Arch Replacement for Cutis Laxa Aortopathy

Abstract

Aortic aneurysms requiring surgery in early childhood are rare. Herein we describe the case of a three-year-old with massive aneurysmal aortic dilation secondary to the rare and often lethal genetic disorder, cutis laxa. Initial thoracic aortic aneurysm gene panel was negative. Parents of the child were not known to be consanguineous, but high-density SNP array revealed several regions of homozygosity. This prompted targeted sequence analysis that identified a novel homozygous missense mutation in the gene for cutis laxa, EFEMP2. The patient underwent aortic valve-sparing aortic root and ascending aorta replacement and total aortic arch replacement, with continuous, moderately hypothermic cardiopulmonary bypass, using a dual cannulation technique. He was discharged well on the third postoperative day and remains free of aneurysmal disease at two-year follow-up.

Case Report: Occurrence of Severe Thoracic Aortic Aneurysms (Involving the Ascending, Arch, and Descending Segments) as a Result of Fibulin-4 Deficiency: A Rare Pathology With Successful Management

“…TAA are very rare in the pediatric population and have primarily been ascribed to autosomal dominant conditions such as the Loeys-Dietz, osteoartheritis-aortopathy, and the neonatal Marfan syndromes ( 6 ). The aneurysms in these conditions typically involve uneven dilation of the aortic root ( 9 ).…”

“…EFEMP2 encodes for the ECM protein fibulin-4. Deficiency of fibulin-4, an elastin-binding ECM protein prominently expressed in the medial layer of large veins, arteries and skin, affects the expression and localization of fibrillary collagen, leading to elastic fiber disarray and aortic aneurysm formation ( 6 , 8 , 14 ).…”

“…The differential diagnosis for several connective tissue disorders associated with arterial tortuosity and aneurysm formation show considerable clinical, histological, and pathophysiological overlap ( 11 ), and therefore, make the differential rather broad and confounding. Different genomic mapping/sequencing approaches have been suggested as the first line approach while investigating these genetically heterogenous disorders ( 6 – 8 , 11 ). With only eight total EFEMP2 mutations previously described ( 6 ), these can be associated with symptomatic aneurysms in early childhood and should be considered by the physician when evaluating an infant or young child with severe aortic dilation.…”

“…Different genomic mapping/sequencing approaches have been suggested as the first line approach while investigating these genetically heterogenous disorders ( 6 – 8 , 11 ). With only eight total EFEMP2 mutations previously described ( 6 ), these can be associated with symptomatic aneurysms in early childhood and should be considered by the physician when evaluating an infant or young child with severe aortic dilation. Previous reports have described a high mortality rate associated with EFEMP2 mutations until early childhood, likely as a result of aortic coarctation or the presence of an aneurysm and compression of airway or pulmonary artery ( 8 , 11 , 13 ).…”

“…Mutations that cause TAA interfere with the function of genes that encode components of the extracellular matrix (ECM) or proteins implicated in the transduction of either mechanical or biochemical signals in vascular smooth muscle cells ( 5 ). The major spectrum of heritable connective tissue diseases related to aortopathy tend to follow an autosomal dominant pattern of inheritance but some mutations (such as those in the EFEMP2 gene, alias FBLN4 ) that result in aneurysms are autosomal recessive in nature ( 6 ).…”