LIVING WITH EHLERS-DANLOS SYNDROME: FOLLOWING A YOUNG BOY THROUGH HIS UPS AND DOWNS ON HIS JOURNEY INTO ADULTHOOD

Abstract

SESSION TITLE: Genetic and Developmental Disorders Case Report PostersSESSION TYPE: Case Report PostersPRESENTED ON: 10/17/2022 12:15 pm - 01:15 pmINTRODUCTION: Ehlers-Danlos syndromes (EDS) are a group of genetic diseases manifesting as various forms of connective tissue disease. Amongst the 13 subtypes, vascular EDS (vEDS) is due to autosomal dominant inheritance of mutated COL3A1 gene, affecting the production of type III collagen. We present a case of a young boy with vEDS from the time of diagnosis and his survival into young adulthood.CASE PRESENTATION: A 25-year-old man presented to pulmonary clinic with the following history: at the age of 16, he presented to a pediatric pulmonary clinic for acute onset shortness of breath, chest tightness, and hemoptysis with a recent elbow tendon and brachial artery rupture following minor trauma. He has no family history of pulmonary diseases. His physical exam was notable for translucent skin, joint hypermobility, long fingers with clinodactyly, acrocyanosis, and no wheezing. Computed tomography scan of the lungs revealed a large cavitary nodule and diffuse smaller lung nodules bilaterally surrounded by ground-glass opacities without lymphadenopathy. Pulmonary function test (PFT) did not show any abnormalities. Biopsy of the lung nodule showed nonspecific inflammation. Extensive rheumatologic markers were all negative. Due to continued hemoptysis, he underwent wedge resection of his left lower lobe, which was complicated by a left pneumothorax that was conservatively managed. Pathological evaluation revealed alveolar hemorrhage with foci of wall destruction. Genetic evaluation finally revealed a heterogenous mutation in COL3A1 gene; he was diagnosed with vEDS. Since the time of diagnosis, he has had recurrent episodes of hemoptysis and three episodes of spontaneous pneumothoraces which required chest tube and talc pleurodesis bilaterally. Subsequent chest imaging and PFTs revealed progressive emphysematous changes with significant bullae, cystic bronchiectasis, and obstructed flow with decreased diffusion capacity, causing persistent dyspnea on exertion. 9 years since the diagnosis, he still has intermittent hemoptysis and chest pain that prompts him to seek frequent emergent medical attention, putting a significant strain on his quality of life.DISCUSSION: VEDS is a rare genetic disease with the frequency of de novo mutations as high as 51%. While gaining a diagnosis poses a challenge in the absence of family history, the burden of this disease stems from the management of its complications. Patients continue to suffer from the physical and psychological strain caused by recurrent complications. Because of its association with catastrophic acute viscus and vascular rupture, vEDS has the worst prognosis of all subtypes.CONCLUSIONS: This case highlights the challenge in diagnosing vEDS caused by a de novo mutation and managing its recurrent complications. Understanding the natural history of vEDS and its complications is crucial for supporting patients and providing an effective management plan.Reference #1: Byers PH, Belmont J, Black J, De Backer J, Frank M, Jeunemaitre X, Johnson D, Pepin M, Robert L, Sanders L, Wheeldon N. Diagnosis, natural history, and management in vascular Ehlers-Danlos syndrome. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):40-47. doi: 10.1002/ajmg.c.31553. PMID: 28306228.Reference #2: Legrand A, Devriese M, Dupuis-Girod S, Simian C, Venisse A, Mazzella JM, Auribault K, Adham S, Frank M, Albuisson J, Jeunemaitre X. Frequency of de novo variants and parental mosaicism in vascular Ehlers-Danlos syndrome. Genet Med. 2019 Jul;21(7):1568-1575. doi: 10.1038/s41436-018-0356-2. Epub 2018 Nov 26. PMID: 30474650.Reference #3: Pepin M, Schwarze U, Superti-Furga A, Byers PH. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med 2000;342:673–680.DISCLOSURES: No relevant relationships by Hadya ElshakhNo relevant relationships by Rammohan GumpeniNo relevant relationships by Stephen KarbowitzNo relevant relationships by Christina Jee Ah RheeNo relevant relationships by Fizza Sajid SESSION TITLE: Genetic and Developmental Disorders Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Ehlers-Danlos syndromes (EDS) are a group of genetic diseases manifesting as various forms of connective tissue disease. Amongst the 13 subtypes, vascular EDS (vEDS) is due to autosomal dominant inheritance of mutated COL3A1 gene, affecting the production of type III collagen. We present a case of a young boy with vEDS from the time of diagnosis and his survival into young adulthood. CASE PRESENTATION: A 25-year-old man presented to pulmonary clinic with the following history: at the age of 16, he presented to a pediatric pulmonary clinic for acute onset shortness of breath, chest tightness, and hemoptysis with a recent elbow tendon and brachial artery rupture following minor trauma. He has no family history of pulmonary diseases. His physical exam was notable for translucent skin, joint hypermobility, long fingers with clinodactyly, acrocyanosis, and no wheezing. Computed tomography scan of the lungs revealed a large cavitary nodule and diffuse smaller lung nodules bilaterally surrounded by ground-glass opacities without lymphadenopathy. Pulmonary function test (PFT) did not show any abnormalities. Biopsy of the lung nodule showed nonspecific inflammation. Extensive rheumatologic markers were all negative. Due to continued hemoptysis, he underwent wedge resection of his left lower lobe, which was complicated by a left pneumothorax that was conservatively managed. Pathological evaluation revealed alveolar hemorrhage with foci of wall destruction. Genetic evaluation finally revealed a heterogenous mutation in COL3A1 gene; he was diagnosed with vEDS. Since the time of diagnosis, he has had recurrent episodes of hemoptysis and three episodes of spontaneous pneumothoraces which required chest tube and talc pleurodesis bilaterally. Subsequent chest imaging and PFTs revealed progressive emphysematous changes with significant bullae, cystic bronchiectasis, and obstructed flow with decreased diffusion capacity, causing persistent dyspnea on exertion. 9 years since the diagnosis, he still has intermittent hemoptysis and chest pain that prompts him to seek frequent emergent medical attention, putting a significant strain on his quality of life. DISCUSSION: VEDS is a rare genetic disease with the frequency of de novo mutations as high as 51%. While gaining a diagnosis poses a challenge in the absence of family history, the burden of this disease stems from the management of its complications. Patients continue to suffer from the physical and psychological strain caused by recurrent complications. Because of its association with catastrophic acute viscus and vascular rupture, vEDS has the worst prognosis of all subtypes. CONCLUSIONS: This case highlights the challenge in diagnosing vEDS caused by a de novo mutation and managing its recurrent complications. Understanding the natural history of vEDS and its complications is crucial for supporting patients and providing an effective management plan. Reference #1: Byers PH, Belmont J, Black J, De Backer J, Frank M, Jeunemaitre X, Johnson D, Pepin M, Robert L, Sanders L, Wheeldon N. Diagnosis, natural history, and management in vascular Ehlers-Danlos syndrome. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):40-47. doi: 10.1002/ajmg.c.31553. PMID: 28306228. Reference #2: Legrand A, Devriese M, Dupuis-Girod S, Simian C, Venisse A, Mazzella JM, Auribault K, Adham S, Frank M, Albuisson J, Jeunemaitre X. Frequency of de novo variants and parental mosaicism in vascular Ehlers-Danlos syndrome. Genet Med. 2019 Jul;21(7):1568-1575. doi: 10.1038/s41436-018-0356-2. Epub 2018 Nov 26. PMID: 30474650. Reference #3: Pepin M, Schwarze U, Superti-Furga A, Byers PH. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med 2000;342:673–680. DISCLOSURES: No relevant relationships by Hadya Elshakh No relevant relationships by Rammohan Gumpeni No relevant relationships by Stephen Karbowitz No relevant relationships by Christina Jee Ah Rhee No relevant relationships by Fizza Sajid