Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene.

BACKGROUND: Cutis laxa is an acquired or inherited condition characterized by redundant, pendulous and inelastic skin. Autosomal dominant cutis laxa has been described as a benign disease with minor systemic involvement. OBJECTIVE: To report a family with autosomal dominant cutis laxa and a young girl with sporadic cutis laxa, both with variable expression of an aortic aneurysmal phenotype ranging from mild dilatation to severe aneurysm or aortic rupture. METHODS AND RESULTS: Histological evaluation of aortic aneurysmal specimens indicated classical hallmarks of medial degeneration, paucity of elastic fibres, and an absence of inflammatory or atherosclerotic lesions. Electron microscopy showed extracellular elastin deposits lacking microfibrillar elements. Direct sequencing of genomic amplimers detected defects in exon 30 of the elastin gene in affected individuals, but did not in 121 normal controls. The expression of mutant elastin mRNA forms was demonstrated by reverse transcriptase polymerase chain reaction analysis of cutis laxa fibroblasts. These mRNAs coded for multiple mutant tropoelastins, including C-terminally truncated and extended forms as well as for molecules lacking the constitutive exon 30. CONCLUSIONS: ELN mutations may cause severe aortic disease in patients with cutis laxa. Thus regular cardiac monitoring is necessary in this disease to avert fatal aortic rupture.

Rapid enlargement of neoaortic root after the Ross procedure in children.

Serial echocardiographic studies from 11 patients who underwent the Ross procedure were reviewed, and the rate of neoaortic annulus size increase was compared with that in a normal population. The rate of growth of the neoaortic annulus after the Ross procedure was significantly greater than that in the normal population.

Acrofacial dysostosis with ambiguous genitalia.

We report on a 46,XY infant with mandibulofacial dysostosis, preaxial and postaxial limb anomalies, urethral stenosis with left hydronephrosis, and ambiguous genitalia with phallic/scrotal transposition. This infant with atypical pre/postaxial acrofacial dysostosis (AFD) is the first to be reported with ambiguous genitalia. The acrofacial dysostoses are a heterogenous group of disorders characterized by varying degrees of mandibulofacial dysostosis with acral limb defects and may represent a polytopic field defect. These disorders have generally been separated on the basis of their limb anomalies into preaxial, postaxial, lethal, and atypical types. Most cases are sporadic, but various causes have been postulated including autosomal dominant and recessive inheritance, a chromosome 2q duplication, and a possible case of diabetic embryopathy. We review the nonfacial/limb anomalies in other cases of AFD and compare them to those of our case, thereby expanding the spectrum of anomalies in these disorders.