SNP Shot: Genomic Insights

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a condition that disrupts the normal development of the lungs and their blood vessels. It primarily affects the alveoli, the numerous tiny air sacs in the lungs, and the alveolar capillaries, the small blood vessels within these sacs. These capillaries are crucial for the exchange of gases: oxygen from inhaled air enters the bloodstream, while carbon dioxide from the bloodstream is released to be exhaled.

In individuals with ACD/MPV, the alveolar capillaries do not develop as they should. There is a significant reduction in the number of capillaries, and the existing ones are often misplaced within the alveolar walls. These irregularities in capillary quantity and position hinder the efficient transfer of oxygen and carbon dioxide.

ACD/MPV also involves other blood vessel abnormalities within the lungs. The pulmonary veins, which carry blood from the lungs to the heart, are often mispositioned and may be abnormally grouped together with the pulmonary arteries, which transport blood from the heart to the lungs. Furthermore, the muscle tissue in the pulmonary artery walls can become overgrown, leading to thicker walls and a narrower channel. This restricts normal blood flow, resulting in high blood pressure in the pulmonary arteries (pulmonary hypertension) and increased workload for the heart.

Many infants with ACD/MPV are born with additional abnormalities. These can include malrotation (abnormal twisting) of the large intestine or other structural defects in the gastrointestinal tract. Cardiovascular and genitourinary problems are also frequently observed in affected individuals.

Infants with ACD/MPV typically show signs of respiratory distress within minutes or hours after birth. They experience difficulty breathing and cyanosis, a bluish discoloration of the skin, mucous membranes, or nail beds due to insufficient oxygen in the blood. Tragically, without lung transplantation, infants with ACD/MPV generally do not survive beyond one year, and most live only for a few weeks.

Inheritance:

ACD/MPV is generally not inherited, and most affected individuals have no family history of the disorder. The genetic changes associated with ACD/MPV typically occur spontaneously during the formation of reproductive cells (eggs and sperm) or in the early stages of fetal development. When ACD/MPV is caused by a mutation or deletion in the FOXF1 gene, having one altered or missing gene copy in each cell is enough to cause the condition. Because individuals with ACD/MPV typically do not live long enough to reproduce, they do not pass on the genetic change to their offspring.

There have been a small number of families identified where multiple siblings have ACD/MPV. The inheritance pattern in these families remains unclear, as the responsible genetic changes have not yet been identified.