The first Japanese case of small airway disease in a patient with autosomal dominant cutis laxa harboring frameshift variant in exon 30 of the elastin gene

Abstract

Abstract Background: Cutis laxa constitutes a diverse group of connective tissue diseases, both inherited and acquired, characterized by loose skin and varying systemic involvement, including pulmonary lesions. While cutis laxa has been linked to conditions like emphysema, asthma, and bronchiectasis, the specific pathological and radiological characteristics underlying pulmonary complications related to cutis laxa remain unclear. Case presentation: A 36-year-old woman, diagnosed with cutis laxa at birth, presented to our outpatient clinic with severe obstructive ventilatory impairment, evident in preoperative pulmonary function tests (expiratory volume in one second (FEV1)/forced vital capacity (FVC): 34.85%). Pulmonary function tests also indicated small airway disease (FEF50%, 7.9%; FEF75%, 5.7%; and FEF25–75%, 6.8%). Computed tomography (CT) revealed pronounced air trapping during expiration, with no discernible emphysematous changes. Exome sequencing was performed to confirm the association between the pulmonary lesions and cutis laxa, revealing a frameshift variant in exon 30 of the elastin gene (ELN). Further analysis employing a parametric response map revealed a longitudinal increase in the percentage of functional small airway disease (fSAD), despite the absence of overt changes in CT findings, specifically air trapping and emphysema. Conclusions: This case highlighted an instance of autosomal dominant cutis laxa arising from a frameshift variant in exon 30 of ELN, accompanied by small airway disease. Comprehensive investigation, utilizing quantitative CT analysis, revealed a longitudinal increase in fSAD percentage with a slight reduction in FEV1. These findings indicate that elastin deficiency may not only diminish elastic fibers in the skin but also be implicated in small airway disease by impacting components of the extracellular matrix in the lungs.