SNP Shot: Genomic Insights

Pulmonary veno-occlusive disease (PVOD) is a condition where the pulmonary veins, the blood vessels carrying oxygenated blood from the lungs to the heart, become blocked (occluded). This blockage results from an abnormal buildup of fibrous tissue within the small veins of the lungs, narrowing them and hindering blood flow. This restricted blood flow causes increased pressure in the pulmonary arteries, the vessels that carry blood from the heart to the lungs for oxygenation. This elevated pressure is known as pulmonary arterial hypertension.

The impaired blood flow in PVOD disrupts the delivery of oxygenated blood to the body, leading to various signs and symptoms. Common symptoms include shortness of breath (dyspnea) and fatigue during physical activity. Additional symptoms can include dizziness, lethargy (lack of energy), difficulty breathing while lying down, and a persistent cough. As PVOD progresses, individuals may experience cyanosis (a bluish skin discoloration), chest pain, fainting episodes, and pulmonary edema (fluid accumulation in the lungs).

Computed tomography (CT) scans can reveal features characteristic of PVOD. One such finding is centrilobular ground-glass opacities in the lungs. Furthermore, abnormal thickening of lung tissues, referred to as septal lines, is often observed. Enlarged mediastinal lymph nodes (lymph nodes in the chest) are also a common finding in individuals with PVOD.

PVOD can develop at any age, and the blood flow problems progressively worsen. The elevated pressure in the pulmonary arteries forces the heart to work harder to pump blood to the lungs, potentially leading to fatal heart failure. The prognosis for individuals with this severe condition is often poor, with many surviving only two years or less after diagnosis.

Inheritance:

When PVOD is caused by mutations in the EIF2AK4 gene, it follows an autosomal recessive inheritance pattern. This means that both copies of the gene in each cell must carry mutations for the disease to manifest. Individuals with autosomal recessive PVOD inherit one mutated copy of the gene from each parent, who are typically carriers and do not exhibit symptoms of the condition. Conversely, mutations in other genes can lead to an autosomal dominant inheritance pattern. In this case, only one copy of the altered gene in each cell is sufficient to cause the disorder. Typically, one parent of an individual with autosomal dominant PVOD has pulmonary hypertension (increased blood pressure in the lung vessels).