Discordant Manifestations of Lymphangioleiomyomatosis and Tuberous Sclerosis Complex in Monozygotic Twins

作者：Amanda M. Jones, Samantha Verling, Elias Bou Farhat, C Girod, Devin Barzallo, D J Kwiatkowski, Thomas N. Darling, Joanna Moss · 发表于：American Journal of Respiratory and Critical Care Medicine · 年份：2025 · DOI：10.1164/ajrccm.2025.211.abstracts.a7499 · 被引用次数：1 · 研究领域：Tuberous Sclerosis Complex Research

Abstract Introduction. Lymphangioleiomyomatosis (LAM) is a disorder affecting primarily women and is distinguished by cystic lung destruction, abdominal tumors (angiomyolipomas), and involvement of the lymphatic system (lymphangioleiomyomas). Sporadic LAM is caused by somatic mutations in the tuberous sclerosis complex (TSC) 1 or 2 genes in an unknown susceptible cell. LAM can also occur in the setting of TSC, an autosomal dominant condition that results from germ line mutations in the TSC1 or TSC2 genes and is characterized by widespread hamartomas in many organs including the brain, heart, skin, kidney, eyes, lung, and liver. Mosaicism for a causative variant in TSC1 or TSC2 occurs in 10%-15% of TSC patients. Case Description. A 41-year-old monozygotic twin was diagnosed at the age of 35 with LAM based on lung cysts, bilateral renal angiomyolipomas, pelvic lymphangioleiomyoma, pelvic chylous ascites, and right chylous pleural effusion. A VEGF-D was sent which was nondiagnostic at 535. She had routine genetic testing for TSC1 and TSC2 which was negative. She was noted on examination to have skin findings on the face which were biopsy proven to be angiofibromas. Her symptoms included chronic dry cough, vaginal chylous drainage, and dyspnea. Lung function was mostly preserved with an FEV-1 post-albuterol of 84% predicted and a DLCO of 72% predicted. Cardiopulmonary exercise test showed no ventilatory limitation or gas exchange abnormality. There were no brain lesions. There we...