Introduction
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a pathological condition characterized by aberrant lung and pulmonary vascular development. The illness impacts many alveoli, which are little air sacs in the lungs, and the capillaries, the minuscule blood vessels within the alveoli. The process by which oxygen from inhaled air enters the bloodstream and is subsequently distributed throughout the body. At the same time, carbon dioxide is removed from the bloodstream and occurs through the alveolar capillaries.
What Are the Causes?
Defects in the FOXF1 gene have been identified as a potential cause of ACD/MPV.
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The protein FOXF1 plays a crucial role in the developmental processes of the lungs and their associated vasculature. The involvement of the FOXF1 protein causes the developmental processes of the gastrointestinal system.
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ACD/MPV arises from mutations occurring in the particular gene, which give rise to a non-functional protein that cannot regulate developmental processes. Consequently, this disruption leads to anomalous development of both the pulmonary blood vessels and the gastrointestinal tract.
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ACD/MPV can also be attributed to a genetic anomaly involving the deletion of genetic material on the long arm of chromosome 16, specifically within this region. The elimination of a single copy of the FOXF1 gene in every cell leads to a decrease in the synthesis of the FOXF1 protein.
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The deficiency of FOXF1 protein significantly impacts the formation of pulmonary blood vessels and gives rise to the primary characteristics of alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV).
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The presence of supplementary abnormalities, such as cardiac malformations, observed in certain children afflicted with this condition might likely be attributed to the absence of other genes within this specific genomic area.
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Like FOXF1, these genes also encode transcription factors that govern the development of different bodily systems throughout prenatal stages.
What Are the Signs and Symptoms of This Condition?
Infants with ACD MPV experience significant respiratory issues and a shortage of oxygen in the blood (hypoxemia) within the first few days of life.
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They have shortness of breath.
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Cyanosis (a disorder characterized by abnormal bluish skin coloring caused by low oxygen levels in the blood).
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High blood pressure in the pulmonary arterial blood vessels (pulmonary hypertension).
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Breathing problems worsen as time advances, and most newborns die from respiratory failure. Infants may not exhibit disease symptoms until weeks or even months after birth, usually when pulmonary hypertension of varying severity is observed.
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Affected infants frequently have additional symptoms, such as twisting of the large intestines.
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Genitourinary symptoms like kidney swelling due to urine backing up (hydronephrosis).
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Cardiovascular symptoms like underdevelopment of the left side of the heart.
What Are the Diagnostic Methods?
ACD MPV should be suspected in any infant with severe cyanosis (hypoxemia) and elevated pulmonary blood pressure (pulmonary hypertension) that is resistant to treatment in the neonatal intensive care unit (NICU).
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Histopathological Examination: An experienced pathologist confirms the diagnosis through a histopathological or tissue examination of lung tissue obtained through a biopsy or autopsy in search of characteristic tissue alterations. A pathologist may observe a lack of capillaries near the alveoli, a thickening of the walls of the alveoli, a misalignment of the pulmonary veins, and an increase in the "muscularization" of the tiny arteries of the lungs.
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Molecular Genetic Testing: In most children, molecular genetic testing can detect the presence of ACDMPV. Molecular genetic testing can detect alterations in the particular gene or changes in the function of the FOXF1 gene that are known to cause this disorder. This testing should also be conducted on the parents to ascertain whether or not they carry the genetic abnormality.
What Are the Consequences of the Specific Condition?
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Capillary Abnormality: The development of alveolar capillaries is impaired in individuals with ACD/MPV. There is a significant reduction in capillaries, and the positioning of the surviving capillaries within the alveolar walls needs to be revised. The presence of irregularities in both the quantity and positioning of capillaries hinders the efficient transfer of oxygen and carbon dioxide.
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Vascular Abnormalities: ACD/MPV is associated with other vascular anomalies in the pulmonary vasculature. The pulmonary veins, responsible for transporting blood from the lungs to the heart, exhibit inappropriate positioning and potential aberrant coalescence with the pulmonary arteries, which carry blood from the heart to the lungs. The muscular tissue inside the pulmonary arteries has the potential to undergo hypertrophy, leading to an increase in the thickness of the arterial walls and subsequently causing a reduction in the diameter of the arterial lumen. The alterations above impede regular blood circulation, resulting in elevated blood pressure within the pulmonary arteries, a condition known as pulmonary hypertension. Consequently, the heart must exert greater effort to maintain adequate blood flow.
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In Newborns: The majority of newborns diagnosed with ACD/MPV have accompanying congenital anomalies. These may encompass anomalous torsion (malrotation) of the colon or other anomalies within the gastrointestinal system. Affected people often have common cardiovascular and genitourinary problems.
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In Infants: Infants diagnosed with ACD/MPV commonly exhibit respiratory distress shortly after birth, typically manifesting within a timeframe ranging from a few minutes to a few hours. Individuals may exhibit symptoms such as dyspnea and cyanosis, characterized by a bluish discoloration of the skin, mucous membranes, or nail beds resulting from inadequate bloodstream oxygenation. In the absence of lung transplantation, it has been observed that children diagnosed with alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) do not typically survive beyond the age of one year. Furthermore, most affected infants have a limited lifespan of only a few weeks.
What Are the Treatment Methods?
Several therapeutic interventions have been employed in neonates diagnosed with alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV).
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They encompass mechanical breathing, nitric oxide administration, and extracorporeal membrane oxygenation (ECMO) implementation.
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The treatments are commonly employed for newborns diagnosed with respiratory distress stemming from various illnesses. Still, their efficacy is inadequate when administered to infants affected by ACDMPV.
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Lung transplants have demonstrated success in a subset of older infants presenting with milder or late-onset alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV).
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Genetic counseling is required for individuals who are impacted by genetic conditions as well as their respective families. The provision of psychosocial assistance for the entire family is crucial.
Conclusion
ACD/MPV is an uncommon and almost always fatal lung developmental disorder. The severity of the patient's hypoxemia and PH (pulmonary hypertension) worsens over time. Although awareness of ACD/MPV is increasing among clinicians, it can be mistaken for idiopathic PH due to the comparable clinical presentation. Whenever the response to medical treatment deviates from what would be expected, a histological examination should be conducted. In addition, an open lung biopsy should preferably be performed prior to initiating ECMO therapy or surgical interventions for co-occurring anomalies. Lung transplantation can be considered for a very small subset of atypical ACD/MPV patients, although survival rates remain disappointing. ACD/MPV is linked to the haploinsufficiency of FOXF1, a transcription factor regulated by SHH that plays a crucial role in early lung development. Despite morphological differences, prenatal or postnatal genetic testing could contribute to earlier detection and permit adequate consultation regarding the prognosis and the decision-making process.
