Alveolo-capillary dysplasia with misalignment of pulmonary veins (alveolar capillary dysplasia With misalignment of pulmonary veins) - Gen FOXF1 and chromosome 16            

Alveolo-capillary dysplasia with misalignment of pulmonary veins (ACD / MPV) is a disease that affects the development of the lungs and blood vessels. Specifically, this process involves the alveoli in the lungs and capillaries in the alveoli. It is through these alveolar capillaries where inhaled oxygen enters the bloodstream for distribution throughout the body and carbon dioxide leaves the bloodstream to be exhaled.

In the ACD / MPV, alveolar capillaries do not develop normally. The number of capillaries is drastically reduced, and capillaries are located incorrectly existing inside the walls of the alveoli. These anomalies in the number of capillaries and location prevent the exchange of oxygen and carbon dioxide. Other abnormalities also occur in the blood vessels of the lungs in the ACD / MPV. The pulmonary veins are poorly positioned and may be abnormally grouped together with the pulmonary arteries. Muscle tissue in the walls of the pulmonary arteries can be covered, which causes the arterial walls are thicker and closer light. These changes limit normal blood flow, causing pulmonary hypertension and requires the heart to pump harder.

Most newborns with ACD / MPV born with additional anomalies. These abnormalities may include a rotation of abnormal bowel or other malformations of the gastrointestinal tract, and cardiovascular and genitourinary anomalies. Newborns with ACD / MPV often develop respiratory failure within a few minutes to a few hours after birth. These individuals manifest breathlessness and cyanosis. Without lung transplant, newborns with ACD / MPV do not survive beyond one year old, and most affected children live only a few weeks.

This may be due to mutations in the gene FOXF1 (forkhead box F1), located on the long arm of chromosome 16 (16q24). The protein encoded from FOXF1 gene is a transcription factor, meaning that binds to specific DNA regions and helps control the activity of many other genes. This protein is important in the development of lung mesenchyme, which arise from embryonic tissue blood vessels of the lung. It is also involved in the development of the gastrointestinal tract.

They have identified at least four mutations in the gene FOXF1 in children with alveolar-capillary dysplasia with misalignment of pulmonary veins (ACD / MPV). Some mutations change promptly amino acids used for protein coding FOXF1. Other mutations inserted or deleted genetic material FOXF1 gene. These mutations result in an inactive protein can not regulate the development, leading to the abnormal formation of the pulmonary blood vessels. Children affected with gene mutations FOXF1 usually also have gastrointestinal abnormalities.

Alveolo-capillary dysplasia with misalignment of pulmonary veins may also be due to a deletion of genetic material on the long arm of chromosome 16 in a region known as 16q24.1. This region includes several genes, including the gene FOXF1. Deletion of one copy of the gene in every cell FOXF1 reduces coding FOXF1 protein. FOXF1 protein deficiency affects the development of the pulmonary blood vessels and leads to the main features of the ACD / MPV. It is believed that the loss of other genes in this region is probably responsible for the additional abnormalities such as heart defects seen in some patients with this disease. Like the FOXF1 gene, these genes also encode transcription factors regulating the development of multiple body systems before birth. 60 percent of children affected, the genetic cause of ACD / MPV is unknown.

This process usually not inherited, and the people most affected have no history of the disease in his family. Genetic changes associated with this disease usually occur during the formation of reproductive cells or early embryonic development. When the disease is due to a genetic mutation or deletion FOXF1, an altered gene or absent in each cell it is sufficient to express the disease. Individuals with ACD / MPV do not transmit to their offspring genetic change because they do not live long enough to reproduce. They have identified a few families in which more than one sibling has ACD / MPV. It is unclear how ACD / MPV is inherited in these families because they have not been identified genetic changes.

Tests performed in IVAMI: in IVAMI perform detection of mutations associated with alveolo-capillary dysplasia with misalignment of pulmonary veins (ACD / MPV), by complete PCR amplification of exons FOXF1 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).