Pulmonary Fibrosis_Interstitial Lung Disease

Gene: FOXF1

Green List (high evidence)

Congenital alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is characterized histologically by failure of formation and ingrowth of alveolar capillaries that then do not make contact with alveolar epithelium, medial muscular thickening of small pulmonary arterioles with muscularization of the intraacinar arterioles, thickened alveolar walls, and anomalously situated pulmonary veins running alongside pulmonary arterioles and sharing the same adventitial sheath. Less common features include a reduced number of alveoli and a patchy distribution of the histopathologic changes. The disorder is associated with persistent pulmonary hypertension of the neonate and shows varying degrees of lability and severity. Affected infants present with respiratory distress resulting from pulmonary hypertension in the early postnatal period, and the disease is uniformly fatal within the newborn period. Additional features of ACDMPV include multiple congenital anomalies affecting the cardiovascular, gastrointestinal, genitourinary, and musculoskeletal systems, as well as disruption of the normal right-left asymmetry of intrathoracic or intraabdominal organs.

Over 50 families reported. Most are sporadic, but a few inherited, generally from mother, incomplete paternal imprinting of this gene has been suggested. Mechanism is LOF, many variants located in the DNA binding domain.
Sources: Expert Review

Created: 24 Jan 2021, 6:41 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Alveolar capillary dysplasia with misalignment of pulmonary veins, MIM# 265380

Publications

• 23505205
• 27071622
• 27855150
• 19500772

Green List (high evidence)

Multiple patients reported, usually de novo, but sometimes familial.
A few studies suggest there is incomplete paternal imprinting of this gene.
Variants result in a loss of function; pathogenic variant types include NMD, truncating, extension and missense.

Created: 24 Jan 2021, 3:29 a.m. | Last Modified: 24 Jan 2021, 3:29 a.m.

Panel Version: 0.6116

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Alveolar capillary dysplasia with misalignment of pulmonary veins (MIM#265380), AD

Publications

• 23505205
• 27071622
• 27855150