Familial pulmonary veno-occlusive disease with a composite biallelic heterozygous EIF2AK4 mutation

• Published in: Revue des maladies respiratoires Vol. 37; no. 10; p. 823
• Main Authors: Treffel, G, Guillaumot, A, Gomez, E, Eyries, M, Petit, I, Chabot, J-F, Chaouat, A
• Format: Journal Article
• Language: French
• Published: France 01.12.2020
• Subjects: Heterozygote; Humans; Hypertension, Pulmonary - diagnosis; Hypertension, Pulmonary - genetics; Hypertension, Pulmonary - therapy; Male; Middle Aged; Mutation; Protein-Serine-Threonine Kinases - genetics; Pulmonary Veno-Occlusive Disease - diagnosis; Pulmonary Veno-Occlusive Disease - genetics; Pulmonary Veno-Occlusive Disease - therapy; Radiography, Thoracic; Severity of Illness Index; Siblings; Pulmonary veno-occlusive disease; Familial; Maladie veino-occlusive pulmonaire; Familiale; Heterozygous; Hypertension pulmonaire; Hétérozygote; Mutation; Pulmonary hypertension
• ISSN: 1776-2588
• DOI: 10.1016/j.rmr.2020.09.004

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. Heritable and sporadic forms have been distinguished. Hypoxemia, profound reduction in the diffusion of carbon monoxide and haemodynamic confirmation of pre-capillary pulmonary hypertension are the major diagnostic criteria. Thoracic CT scanning and a response to pharmaceutical therapy provide additional information to confirm the diagnosis. A 52-year-old patient, three of whose siblings had pulmonary hypertension, was admitted with dyspnoea, malaise and palpitations. Right heart catheterisation confirmed pre-capillary pulmonary hypertension. A search for an EIF2AK4 mutation was carried out, and this showed a composite biallelic heterozygous mutation compatible with the diagnosis of familial PVOD, identical to that showed in one of his brothers. Given the signs of severity of the disease and the diagnosis of PVOD, whose response to pharmaceutical therapy is often poor, the patient was placed on a waiting list for lung transplantation. Despite a similar diagnosis in 3 brothers and follow-up proposed 11 years before the diagnosis, pulmonary hypertension appeared within a few weeks and led immediately to a severe clinical situation. Annual clinical and echocardiographic monitoring had been strongly advised to the patient, but had not allowed diagnosis at a mild or moderate stage of the disease. This clinical case shows that the identification of factors predicting the development of heritable PVOD at a pre-symptomatic stage is an important issue for clinical research.