FBLN5-Related Cutis Laxa Syndrome: A Case with a Novel Variant and Review of the Literature

Abstract

<b><i>Introduction:</i></b> <i>FBLN5</i>-related cutis laxa is a very rare, autosomal recessive syndrome that is characterized by loose, wrinkled, and redundant skin, sagging cheeks, emphysema, aortic or pulmonary artery abnormalities, inguinal hernia, and diverticula of the gastrointestinal and urinary tract. <b><i>Case Presentation:</i></b> In this study, we report an 8-year-old Turkish girl with a novel homozygous missense variant in the <i>FBLN5</i> gene, c.862G>T, p.(Asp288Tyr). Her unaffected parents were carriers of the same variant. The patient had loose skin, short stature, broad eyebrows, large ears, inguinal hernia, frequent respiratory tract infections, a history of peripheral pulmonary artery stenosis, and fourth finger contractures on both hands. <b><i>Discussion:</i></b> To our knowledge, 8 families have been reported to date, and this family is the third Turkish family with <i>FBLN5</i>-related cutis laxa. In addition to the classical findings of cutis laxa, the patient had fourth finger contractures on both hands. This report contributes to the ongoing clinical and genetic characterization of <i>FBLN5</i>-related cutis laxa.

Effect of Aging, Sex, and Gene (Fbln5) on Arterial Stiffness of Mice: 20 Weeks Adult Fbln5-knockout Mice Have Older Arteries than 100 Weeks Wild-Type Mice

“…2) show that the Fbln5-knockout results in more severe waviness loss than aging from 20 weeks to 100 weeks for all the five investigated locations, which explains the higher 'arterial age' of 20 weeks mice with Fbln5 -/than 100 weeks mice with Fbln5 +/+ . These results are also consistent with the effect of Fbln5 mutations on the abnormal looseness and wrinkling of skins in both mice 7,8 and humans 11,36,37 with Fbln5-related Cutis Laxa Syndrome. Thus, the knock-out of Fbln5 gene may be considered as a super-aging effect.…”

“…The protein Fibulin-5 (Fbln5) is an extracellular elastin-associated protein that connects to integrins and localizes tropoelastin to microfibrils as shown in the pioneering work by Yanagisawa et al 7 and Nakamura et al 8 . Abnormal mutations of Fbln5 gene could results in cutis laxa syndrome in humans [9][10][11] . The Fbln5 deficiency alters arterial microstructures by disrupting the integrity of elastic lamellae 7,8,12 , which results in elongated and tortuous central arteries.…”