Filamin A (FLNA) gene mutation-associated disease: results of a multicenter study

Introduction. Pathogenic variants of the FLNA gene cause damage to various organs and systems formed in the embryonic period. The most frequently affected organs are the brain (epilepsy), cardiovascular system (congenital heart defects, pulmonary hypertension — PH), and lungs (emphysema).

The aim of the study: genetic, clinical, laboratory, and instrumental characteristics of patients with a disease caused by pathogenic variants of the FLNA gene.

Materials and methods. Six girls with identified pathogenic variants of the FLNA gene were observed. The methods used: genealogical, whole exome sequencing, Sanger sequencing, electroencephalography, brain MRI, echocardiography, right heart catheterization with determination of pressure and resistance in the pulmonary circulation and pulmonary capillary wedge pressure, CT of the chest organs.

Results. The article presents the results of a molecular genetic study of the FLNA gene. All patients were diagnosed with periventricular nodular heterotopia and psychomotor retardation, 2 of them had epilepsy; 4 children had heart valve dysplasia; 3 had patent ductus arteriosus, 3 had septal defects, 2 had bicuspid aortic valve, 5 had pulmonary hypertension; 5 had pulmonary emphysema; 1 had congenital diaphragmatic hernia. Two patients died during the observation period.

Conclusion. Diagnosis and observation of patients with pathogenic variants of the FLNA gene is a challenge for a multidisciplinary team of doctors at a multidisciplinary pediatric hospital. The presented cohort of 6 patients reflects the most typical manifestations of this pathology, the severity and rate of development of disease in infants.

Compliance with ethical standards. The study was conducted in accordance with the Helsinki Declaration (2013) and Federal Law No. 152-FZ of July 27, 2006 (as amended on December 31, 2017) “On Personal Data”. Voluntary written informed consent was obtained from the patients’ legal representatives.

Contribution:
Miroshnichenko V.P. — patient management, text writing, material collection and data processing, reviewing publications on the topic;
Ovsyannikov D.Yu. — patient management and consultations, text writing, material collection and data processing, concept, text editing;
Abramyan M.A. — patient management, concept, text editing;
Kuzenkova L.M. — text editing, patient management, assessing the neurological status of patients;
Aisina V.A. — analysis and interpretation of electroencephalography data, collecting material and processing data;
Boytsova E.V. — reviewing publications on the topic;
Gitinov Sh.A. — patient management, material collection and data processing;
Gneusheva O.A. — patient management, material collection and data processing;
Gorbunov A.V. — neuroimaging results assessment, material collection and data processing;
Gorev V.V. — medical care organization for patients;
Ivanova A.V. — patient management, material collection and data processing;
Kovalev I.A. — patient consultation, material collection and data processing, medical care organization for patients;
Kondakova O.B. — patient consultation, material collection and data processing;
Kotlukova N.P. — patient consultation, concept, material collection and data processing;
Kravchenko N.E. — review of publications on the topic;
Kuznetsova A.A. — patient consultation, material collection and data processing;
Lyalina A.A. — text editing, assessment of neurological status and phenotype of patients;
Miklashevich I.M. — patient management, material collection and data processing;
Petrova S.I. — patient consultation, material collection and data processing;
Pushkov A.A. — molecular genetic diagnostics, analysis and processing of molecular genetic diagnostics results;
Simonova O.I. — patient consultation, material collection and data processing;
Solomatina N.M. — patient management, material collection and data processing;
Strelnikova V.A. — material collection and data processing;
Suetina O.A. — review of publications on the topic;
Telezhnikova N.D. — patient management, material collection and data processing;
Trunina I.I. — patient consultation, material collection and data processing;
Savostyanov K.V. — analysis and processing of molecular genetic diagnostics results, concept, text editing.
All co-authors — responsibility for theintegrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: April 22, 2025
Accepted: May 28, 2025
Published: August 20, 2025

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