Congenital pulmonary lymphangiectasia (CPL) is a rare developmental disorder that is present at birth (congenital). Affected infants have abnormally widened (dilated) lymphatic vessels within the lungs. The lymphatic system helps the immune system in protecting the body against infection and disease. It consists of a network of tubular channels (lymph vessels) that drain a thin watery fluid known as lymph from different areas of the body into the bloodstream. Lymph accumulates in the tiny spaces between tissue cells and contains proteins, fats, and certain white blood cells known as lymphocytes.
Infants with CPL often develop severe, potentially life-threatening, respiratory distress shortly after birth. Affected infants may also develop cyanosis, a condition marked by abnormal bluish discoloration of the skin that occurs because of low levels of circulating oxygen in the blood. The exact cause of CPL is unknown.
CPL can occur as a primary or secondary disorder. Primary pulmonary lymphangiectasia can occur as isolated congenital defect within the lungs or as part of a generalized form of lymphatic vessel malformation (lymphangiectasia) that affects the entire body, usually associated with generalized lymphedema. Secondary CPL occurs secondary to a variety of heart (cardiac) abnormalities, and/or lymphatic obstructive forms.
Much of the older medical literature suggests that CPL has an extremely high mortality rate. However, recent studies suggest that the disorder does not have as poor a prognosis as described and that symptoms may improve with age in some cases.
Symptoms associated with CPL often develop during the newborn (neonatal) period shortly after birth. During intrauterine period, the occurrence of non-immune hydrops fetalis associated with pleural effusion may be linked to CPL. In some cases, symptoms develop later during infancy. The symptoms of CPL vary in severity from case to case; in most cases, the earlier the presentation the more severe the symptoms.
Affected infants often develop severe respiratory failure and abnormal bluish discoloration of the skin that occurs because of low levels of circulating oxygen in the blood (cyanosis). Infants with CPL may also exhibit coughing or wheezing, progressive difficulty breathing (dyspnea), coughing up blood (hemoptysis), and swelling due to accumulation of lymphatic fluid (lymphedema). Affected infants may exhibit growth failure during infancy.
Additional symptoms eventually develop including an abnormally rapid rate of breathing (tachypnea), chylous pleural effusion, known as chylothorax and recurrent respiratory infections. Chyle is a fat-laden cloudy fluid that is absorbed during digestion by the lymphatic vessels located around the intestine. Chylothorax is the accumulation of chyle or lymph fluid in the pleural cavity. Chyle is composed by fats (mainly phospholipids), proteins (albumin in particular), and a significant amount of lymphocytes. Chyle normally flows through lymphatic vessels into the upper chest (thoracic duct) and is then deposited into veins, where it mixes with blood. In some cases, chyle may accumulate in the abdomen causing chylous ascites.
Some infants with CPL may develop heart abnormalities including a limited ability to circulate blood to the lungs and the rest of the body resulting in fluid buildup in the heart, lung and various body tissues (congestive heart failure).
Some infants with CPL develop gastroesophageal reflux, a digestive disorder characterized by the passage or flowing back (reflux) of the contents of the stomach or small intestines (duodenum) into the esophagus. The esophagus is the tube that carries food from the mouth to the stomach (esophagus). Symptoms of gastroesophageal reflux may include a sensation of warmth or burning rising up to the neck area (heartburn or pyrosis), swallowing difficulties (dysphagia), and chest pain. This problem is a possible complication of CPL, but not a direct consequence or typical symptom.
The exact cause of CPL is unknown. Most cases occur randomly, for no apparent reason (sporadically). The disorder may be caused by a congenital defect in the development of the lung or result from obstruction of the lymph vessels in the lungs (pulmonary lymphatics). Some cases have been associated with genetic multisystem disorders including Noonan syndrome, Turner syndrome, Hennekam syndrome or Fryns syndrome. CPL may be inherited as dominant, recessive, or X-linked inheritance pattern.
Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.
X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and manifest mostly in males. Females that have a defective gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the defective gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a defective gene he will develop the disease.
Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.
If a male with X-linked disorders is able to reproduce, he will pass the defective gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.
Pulmonary lymphangiectasia may occur as a secondary condition to a variety of heart (cardiac) disorders including hypoplastic left heart syndrome, cor triatum, and congenital mitral valve stenosis. Infectious agents have also been suggested as a possible cause of this disorder.
According to some reports CPL occurs more often in males than females. However, the data is not conclusive and CPL may occur in males and females in equal numbers. The exact number of cases of CPL is unknown. In the past, the disorder was associated with high mortality in the newborn period. CPL was first described in the medical literature in 1856.
A diagnosis of CPL may be made based upon a thorough clinical evaluation, identification of characteristic symptoms and a variety of specialized imaging tests. These may include high resolution helical chest computed tomography (CT) scans. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of an organ's tissue structure. In individuals with CPL, CT scans may reveal fluid build up in the chest cavity or lung tissue, showing the characteristic diffuse thickening of the interstitium. An imaging procedure called lymphoscintigraphy may be used to provide pictures of the lymphatic system, and it is very useful to detect diffuse aspects of congenital lymphatic dysplasia, such as lymphedema.
If pleural effusion is present, bronchoscopy and lung biopsy may be considered. During bronchoscopy, a thin, flexible tube (bronchoscope) is inserted through the nose or mouth, allowing a physician to examine the throat, larynx, trachea and lower airways. Lung biopsy involves the surgical removal and microscopic evaluation of affected lung tissue.
The treatment of CPL is symptomatic and supportive. Newborns with serious complications may require a variety of procedures shortly after birth including the use of a machine that creates a controlled flow of air (continuous positive airway pressure, CPAP) to an affected individual's airways to support spontaneous breathing or the placement of a tube into the windpipe (trachea) to assist breathing performing mechanical ventilation (tracheal intubation). In some cases, at birth the immediate drainage of excess fluid from the chest cavity (pleural effusion) with assisted ventilation may improve respiratory distress. A chest tube may be inserted to drain fluid in some cases.
As affected infants age supplemental oxygen may be necessary. Symptomatic treatment for associated conditions such as coughing, wheezing and recurrent infections may also be necessary. Affected children should be monitored for the development of bronchitis. Since nutritional considerations can play a role in limiting lymphatic production, nutritional supplementation may also be recommended.
Since nutritional considerations can play a role in limiting lymphatic production, nutritional supplementation with Medium Chain Triglycerides (MCT) may also be recommended
Researchers are studying the use of drugs such as octreotide and antiplasmin for the treatment of individuals with pulmonary lymphangiectasia. More research is necessary to determine the long-term safety and effectiveness of these potential treatments for individuals with pulmonary lyphangiectasia.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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Contact for additional information about congenital pulmonary lymphangiectasia:
Carlo Bellini, MD, PhD
Department of Pediatric Science
University of Genoa, Italy
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