alveolar capillary dysplasia with misalignment of pulmonary veins

Alveolar capillary dysplasia with misalignment of pulmonary veins is a rare and fatal developmental lung disorder that primarily affects newborns. It is characterized by severe respiratory distress due to refractory hypoxemia and pulmonary arterial hypertension. Genetic changes in the FOXF1 gene, inherited in an autosomal dominant manner, underlie the condition. In very rare cases, it affects fewer than 1 in 1,000,000 people, and its presentation is usually in the neonatal period.

The clinical picture is dominated by severe pulmonary findings, with nearly all affected newborns exhibiting alveolar capillary dysplasia, respiratory distress, pulmonary arterial hypertension, and misalignment of the pulmonary veins. In addition, some infants show signs of cardiac involvement such as hypoplastic left heart, patent ductus arteriosus, or pulmonary valve atresia. Gastrointestinal anomalies like intestinal malrotation and omphalocele may also occur, while a subset of individuals experience global developmental delay, reflecting cognitive and neurological challenges. Not all individuals experience every feature, and severity varies considerably.

This condition is caused by pathogenic variants in the FOXF1 gene, which plays a crucial role in lung development. It is inherited in an autosomal dominant pattern, meaning that a single altered copy of the gene is sufficient to disrupt normal pulmonary vascular and airway development. Although the de novo rate is not specified, many cases may arise from new genetic changes, and affected individuals or families are encouraged to seek a consultation with a genetic counselor to understand the implications and recurrence risks.

Currently, management focuses on supportive care and symptom management since there are no approved or foundational treatments specific to this condition. Treatment is tailored to each individual and typically involves a multidisciplinary team that may include neonatologists, cardiologists, and pulmonologists. Regular surveillance is an essential part of long-term care, helping to identify potential complications as they develop. Families are encouraged to discuss treatment options and supportive strategies with their healthcare team as well as seek genetic counseling.

The outlook for affected individuals is generally poor, with the condition being fatal in the neonatal period in most cases. However, outcomes vary significantly, and not all individuals experience every complication. With current standards of care, outcomes described in medical literature continue to evolve as supportive and multidisciplinary interventions improve. Families are encouraged to connect with specialists, including genetic counselors, to better understand the potential course and to receive guidance on the next steps for care.

There are several clinical trials currently underway exploring new treatment approaches for this condition. Individuals interested in participating in research or learning more about ongoing clinical investigations are advised to consult ClinicalTrials.gov or speak with their care team regarding eligibility.