Case Report: genotype-phenotype correlations in FLNA mutations: insights from a case of multisystem dysfunction

Filamin A (FLNA) mutations are associated with the development of numerous diseases and disorders. Although recent studies have shed light on genotype-phenotype relationships, the evidence remains fragmented.

Herein, we report the case of a male infant with an FLNA nonsense mutation (c.5265C>G; p.Tyr1755*) identified through trio whole-exome sequencing. The patient exhibited multisystem dysfunction, including periventricular nodular heterotopia, congenital heart disease (perimembranous ventricular septal defect), congenital short bowel syndrome, lung disease, and fatal sepsis. We analyzed this case along with a systematic review of 62 cases of male patients with FLNA mutations to explore genotype-phenotype relationships. Results: Following the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines, the variant was classified as likely pathogenic (PVS1, PM2, and PP3). Segregation analysis confirmed maternal inheritance. Standard genetic testing (karyotype and CGH-array) results were unremarkable.

This case expands the phenotypic spectrum of FLNA deficiency, linking a nonsense mutation to a severe clinical course with fatal complications such as necrotizing enterocolitis and sepsis, highlighting the need for vigilant multi-organ monitoring.