Novel FBLN5 Mutation of Congenital Autosomal Recessive Cutis Laxa With Isolated Right Ventricular Non-Compaction (RVNC): New Findings on Echocardiographic Speckle-Tracking Strain Imaging of RVNC

Abstract

We report on a novel mutation in a two-year-old child with autosomal recessive cutis laxa with severe generalized laxity of the skin, prematurely aged appearance, conjunctival chalasia, episodes of severe rectal prolapse, isolated right ventricular non-compaction, (RVNC), significant pulmonary hypertension at the systemic arterial pressure level, severe tricuspid regurgitation, corpulmonale secondary to recurrent pulmonary infections, and mixed pulmonary fibrosis and emphysema. Next generation sequencing of cutis laxa genes identified a novel homozygous mutation in the FBLN5 gene (homozygous sequence alteration of c.907C > T [p. Gin303*] FBLN5 [ENST00000342058]). Despite severe and generalized disorder in the patient's connective tissues, she had no primary valvar or vascular abnormalities in the heart. Complete speckle-tracking strain imaging (SI) by two-dimensional echocardiography showed decreased systolic longitudinal and transverse strain in the involved segment of the right ventricle (RV).

Clinical and Molecular Delineation of Cutis Laxa Syndromes: Paradigms for Elastic Fiber Homeostasis

“…Other craniofacial features include a convex nasal ridge, large ear lobules, and micrognathia (Fig. 13.1) (Loeys et al 2002;Kantaputra et al 2014;Malakan Rad et al 2016;Van Maldergem and Loeys 1993). FBLN5-related CL has a poor prognosis with childhood mortality rates between 30-50%, mainly attributable to cardiopulmonary failure and hollow visceral diverticula (Loeys et al 2002;Elahi et al 2006;de Schepper et al 2003;Van Maldergem et al 1988).…”

“…In most cases, panlobular emphysema develops during early childhood, but it can already be present in the neonatal period (Van Maldergem et al 1988). Recurrent lower respiratory infections resulting in pneumonia are reported in most patients (Loeys et al 2002;Kantaputra et al 2014;Malakan Rad et al 2016;Elahi et al 2006;de Schepper et al 2003). Supravalvular aortic stenosis and peripheral pulmonary artery stenosis are the most common cardiovascular abnormalities.…”