Variações fenotípicas em quatro irmãos com fibrose cística com as mutações R1162X e S4X no gene CFTR: Discussão clínica de uma série de casos

Abstract

Cystic fibrosis is a multisystem autosomal recessive genetic disorder caused by pathogenic variants in the CFTR gene, commonly associated with chronic respiratory disease, recurrent infections, and exocrine pancreatic insufficiency, with marked phenotypic variability across individuals. This study aimed to describe and compare clinical presentation, nutritional outcomes, exacerbations, and pulmonary function in four siblings with cystic fibrosis carrying the rare nonsense CFTR variants R1162X and S4X. This is a descriptive observational case report based on data extracted from electronic medical records at a tertiary referral center, including clinical, laboratory, anthropometric, treatment-related, and spirometric parameters. Results showed that, despite shared genotype and similar family/environmental background, there was substantial clinical variability, particularly regarding nutritional status, hospitalization frequency, and lung function trajectory. All patients presented exocrine pancreatic insufficiency and recurrent airway colonization with Staphylococcus aureus and Pseudomonas aeruginosa; however, female patients showed poorer nutritional status, greater clinical instability, and worse pulmonary function evolution when compared with male patients. Additionally, one female patient used a CFTR modulator therapy (elexacaftor/tezacaftor/ivacaftor) by family decision, although robust evidence for this specific genotype is lacking, highlighting the need for careful monitoring and further research on rare mutations. In conclusion, factors beyond genotype—potentially related to biological sex and the infection–inflammation–nutrition interplay—may significantly influence cystic fibrosis expression, supporting an individualized management approach.