Pulmonary arterial hypertension

Gene: FLNA

Green List (high evidence)

Comment on list classification: As reviewed by Karen Stals, there are more than 3 unrelated individuals with monoallelic variants in FLNA and pulmonary hypertension. Hemizygous male and heterozygous females are affected (with variable penetrance and age of onset). Based on available evidence, this gene should be promoted to Green at the next update.

Created: 8 May 2026, 2:37 p.m. | Last Modified: 8 May 2026, 2:46 p.m.

Panel Version: 4.11

PMID: 40641615 Cai et al., 2025
29yo female (Chinese?) patient with pulmonary hypertension and a heterozygous de novo FLNA c.718 C > T, p.Q240* variant. She presented with telangiectasia, cyanosis of the lips, and hypermobility. At the age of 12, she was diagnosed with precapillary pulmonary hypertension, and patent ductus arteriosus (PDA).

PMID: 39510553 Stourm et al., 2025
Report of 9 French patients (8 female) with moderate to severe pre-capillary pulmonary hypertension, diagnosed at 0-69 years (median 36 years). Associated conditions included epilepsy (n=5), PVNH (n=7), valvular heart disease (n=8), congenital heart diseases (n=4), thrombocytopenia (n=4) and hyperlaxity (n=4). All patients carried LOF FLNA variants: stop-gain, frameshift, canonical splice - all P/LP according to ACMG criteria.

PMID: 30557962 Calcaterra et al., 2018
Progressive pulmonary disease in a male infant harbouring a FLNA c.7391_7403del; (p.Val2464AlafsTer5) variant. He developed significant lung disease resulting in emphysematous lesions and perivascular and interstitial fibrosis. He also exhibited general muscular hypotonia, bilateral inguinal hernia, and deformities of the lower limbs (pes tortus congenitalis and hip dysplasia). Brain MRI showed periventricular nodular heterotopia.

FLNA is associated with multiple X-linked (dominant and recessive) disease entities in OMIM. Pulmonary incompetence is a feature of several FLNA-related disorders, e.g., Cardiac valvular dysplasia, X-linked, OMIM:314400.

Created: 8 May 2026, 2:31 p.m. | Last Modified: 8 May 2026, 2:42 p.m.

Panel Version: 4.10

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
pulmonary hypertension, MONDO:0005149; Cardiac valvular dysplasia, X-linked, OMIM:314400

Publications

• 40641615
• 39510553
• 30557962

Green List (high evidence)

Multiple papers report loss of function FLNA variants as a cause of neonatal/childhood pulmonary hypertension (see PMID: 30547349), GeneReviews FLNA deficiency page lists pulmonary findings including pulmonary hypertension in list of clinical features.
Sources: Literature

Created: 28 Apr 2026, 12:23 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Pulmonary hypertension; respiratory failure

Publications

• PMID: 30547349
• PMID: 28457522

Variants in this GENE are reported as part of current diagnostic practice