P3677Heritable veno-oclusive pulmonary disease in iberian romani patients: the difficulty of genetic counseling and its impact in the perpetuation of the disease

Abstract

Abstract Pulmonary veno-oclussive disease (PVOD) is a rare form of pulmonary hypertension of poor prognosis and difficult diagnosis. A founder mutation in EIF2KA4 gene has been described in Iberian Romani patients with familial PVOD. Aims genetically and clinically characterize a cohort of Iberian Romani patients with familial PVOD. To perform the family screening, analyze the phenotype and socio-cultural determinants which may influence on disease's course and spreading. Methods Patients with familial PVOD were included from November 2011 until February 2019. Clinical and survival data were obtained from the Spanish National Registry of PAH. Genetic analysis of EIF2KA4 was performed in patients and relatives. Results 13 index cases were included, all of them Iberian Romani, carrying the founder mutation (p.Pro1115Leu) in EIF2KA4. Genetic screening revealed 74 of healthy heterozygotes and 13 homozygotes: among them 10 affected and 3 unaffected at baseline assessment (7, 28 and 37 years old). More than half of their family members, including one complete family, refused genetic screening. The survival free of transplant or death was 77.3% and 52.4%, at 1 and 3 years, respectively. Baseline characteristics Total n=23 Age, years (SD) 23.6 (11.8) Male sex, % 52.2 Functional class NYHA III-IV, % 85 Pulmonary vascular resistance, UW (SD) 10 (5.4) DLCO, % 31.1 6MWT, meters (SD) 352.4 (160) Lung transplant, % 47.8 Survival free of transplant 3 years, % 52.4 DLCO, diffusing capacity for carbon monoxide; 6MWT, 6-minute walk test. Conclusions Patients were seriously ill from a young age. They have early pregnancy and high number of children. The high frequency of endogamy in the Romani population is likely to have an important impact on the transmission of PVOD, as it would favor the appearance of new homozygous carriers. Currently, our major concern is the low range of family members that accepted to be studied, more than 50% of family members rejected genetic studies and counseling.