[MIM 265 380]

Extremely rare (less than 100 published cases). De novo mutation (90 %) or autosomal dominant transmission of a mutation of the FOXF1 gene (16q24.1) (60 %) or of the non-coding long RNA's LINC01081 and LINC01082 that amplify it. Disorder of the pulmonary development characterized by neonatal respiratory distress, associating refractory hypoxemia with a severe pulmonary arterial hypertension.

Typical clinical presentation: refractory hypoxemia from birth, most often in a full-term newborn.

Ultrasound: suprasystemic pulmonary hypertension.

Familial forms have been reported, as well as associated abnormalities, including genitourinary, gastrointestinal and cardiovascular ones (50-80 % of cases).

The diagnosis is based on the histology showing a developmental anomaly of the pulmonary capillaries (causing an increased pulmonary vascular resistance with an abnormal development of the muscular cells of the pulmonary arteries) and a lack of alignment of the pulmonary veins: they stay centrolobular close to the broncho-arterial axis, although their normal position is in the nterlobular septum.

Generally death occurs rapidly  due to severe hypoxemia and pulmonary arterial hypertension. A few cases with later onset (a few weeks) have been described.

Anesthetic implications:

management of a neonate with severe pulmonary hypertension (most often associated with a right-to-left shunt); pulmonary biopsy.

References : 

-        Savey B, Jeanne-Pasquier C, Dupont-Chauvel P, Maragnes P, Bellot A, Guillois B.
Dysplasie alvéolo-capillaire avec mésalignement des veines pulmonaires : une cause de cyanose néonatale réfractaire létale.
Arch Péd 2015 ; 22 : 185-90

-        Abu-El-Haija A, Fineman J, Connolly AJ, Murali P, Judge LM, Slavotinek AM. 
Two patients with FOXF1 mutations with alveolar capillary dysplasia with misalignment of pulmonary veins and other malformations: two different presentations and outcomes. 
Am J Med Genet 2018; 176A: 2877-81.

Updated: October 2021