A Patient With Pulmonary Hypertension Carrying FLNA Loss-of-Function Variant

Area of Science:

• Genetics
• Cardiology
• Pulmonology

Background:

• Pulmonary hypertension (PH) is a complex condition with diverse etiologies.
• Filamin A (FLNA) gene variants have been implicated in various genetic disorders.
• Specific phenotypic associations with FLNA loss-of-function variants in PH are emerging.

Purpose of the Study:

• To highlight the unique clinical presentation of patients with PH and FLNA loss-of-function variants.
• To underscore the importance of FLNA genetic screening in a subset of PH patients.
• To present a clinical case consistent with previously reported FLNA-associated phenotypes.

Main Methods:

• Review of existing literature on FLNA gene variants and associated phenotypes.
• Clinical case presentation.
• Analysis of phenotypic features in relation to genetic findings.

Main Results:

• Patients with PH and FLNA loss-of-function variants exhibit distinct pulmonary findings, including lung parenchymal abnormalities and emphysema.
• Extrapulmonary manifestations are common and include dysmorphic facial features, epilepsy, congenital heart defects, valvular and aortic diseases, thrombocytopenia, and periventricular nodular heterotopia (PVNH).
• The described clinical case shares significant phenotypic overlap with the findings reported by Stourm et al.

Conclusions:

• Loss-of-function variants in the FLNA gene are associated with a recognizable spectrum of pulmonary and extrapulmonary abnormalities in patients with PH.
• FLNA genetic screening should be considered in patients diagnosed with PH who present with the characteristic phenotypic features described.
• Early identification of FLNA variants can aid in diagnosis and management of these complex cases.