About CLAs

complex lymphatic anomalies (CLAs)

Complex lymphatic anomalies (CLAs) are a group of rare lymphatic conditions that can affect multiple parts of the body, including bones, organs, soft tissues, and central lymphatic pathways.

While these conditions share some similarities, each has unique characteristics and can affect people differently. Even individuals with the same diagnosis may experience different symptoms depending on which parts of the body are involved.

Understanding the differences between these conditions can help patients and families better understand their diagnosis and navigate treatment and care. The information below provides an overview of the major types of complex lymphatic anomalies currently recognized by specialists.

generalized lymphatic anomaly (GLA)

Formerly known as lymphangiomatosis

Generalized lymphatic anomaly (GLA) is characterized by lymphatic malformations that occur in more than one area of the body. It commonly affects soft tissues, bones, and organs such as the spleen.

GLA may be present at birth but is often diagnosed during childhood or young adulthood. Some people develop abnormal fluid buildup around the lungs, heart, or abdomen. Others may experience loss of lymphatic fluid through the intestines or changes in immune cell levels.

Bone involvement is common in GLA, particularly in the ribs and spine. Unlike some other complex lymphatic anomalies, GLA usually does not cause progressive disappearance of bone, and fractures are uncommon.

Researchers have identified somatic changes (mutations) in the PIK3CA gene in many individuals with GLA.

Gorham-Stout disease (GSD)

Formerly called vanishing bone disease

Gorham-Stout disease (GSD) is characterized by progressive loss of bone. The condition most often affects the head, neck, spine, ribs, and chest, although other bones may also be involved.

Symptoms vary depending on which bones are affected and how much bone loss occurs. Some individuals experience pain, fractures, fluid buildup around the lungs or heart, or neurological symptoms when the disease affects the skull or spine.

GSD can progress rapidly in some people but may stabilize on its own in others.

Researchers believe that somatic changes (mutations) in the KRAS gene contribute to many cases of GSD.

kaposiform lymphangiomatosis (KLA)

Kaposiform lymphangiomatosis (KLA) is a rare and often more aggressive complex lymphatic anomaly. It shares features with both generalized lymphatic anomaly (GLA) and central conducting lymphatic anomaly (CCLA), but has distinct characteristics that make it a separate condition.

KLA commonly affects the chest and can cause significant fluid buildup, bleeding complications, and progressive disease. Chest involvement is more common in KLA than in many other complex lymphatic anomalies, and symptoms often arise from disease affecting the lungs and surrounding tissues.

KLA can behave differently from other lymphatic conditions, making early evaluation by specialists experienced in complex lymphatic anomalies especially important. Certain laboratory findings may also help support a diagnosis. For example, some individuals with KLA have elevated levels of angiopoietin-2 (Ang2), a protein involved in the growth and function of blood and lymphatic vessels.

Researchers have identified somatic changes (mutations) in genes such as NRAS, CBL, and HRAS in some individuals with KLA.

central conducting lymphatic anomaly (CCLA)

Central conducting lymphatic anomaly (CCLA) affects the large lymphatic vessels that transport lymphatic fluid throughout the body. These vessels may be enlarged, malformed, or unable to move lymphatic fluid effectively.

As a result, lymphatic fluid can leak or flow backward into surrounding tissues. Common symptoms include fluid around the lungs, swelling in the legs and feet, abdominal fluid buildup, and loss of lymphatic fluid through the intestines.

CCLA may occur on its own or as part of another genetic condition. Researchers have identified both inherited (germline) and acquired (somatic) genetic changes that may contribute to CCLA, including changes in EPHB4, MDFIC, ARAF, KRAS, and BRAF.

generalized lymphatic dysplasia (GLD)

Generalized lymphatic dysplasia (GLD) is a rare lymphatic disorder characterized by widespread abnormalities of the lymphatic vessels throughout the body.

Unlike several other complex lymphatic anomalies, GLD does not typically involve the bones. Instead, it may affect the lungs, intestines, skin, and other organs.

Common complications include fluid buildup around the lungs, abdomen, or heart, as well as swelling of the limbs or face. Symptoms can range from mild to severe depending on which areas of the body are affected.

Changes in the PIEZO1 gene have been identified as a cause of some forms of GLD.

every patient's experience is different

Although these conditions have distinct features, no two patients experience them in exactly the same way. Symptoms, disease progression, and treatment needs can vary significantly from person to person.

If you or a loved one has been diagnosed with a complex lymphatic anomaly, you are not alone. Connecting with experienced specialists, trusted information, and a supportive community can help you better understand your diagnosis and navigate the journey ahead.

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