SNP Shot: Genomic Insights

Alagille syndrome is a genetic condition that can impact the liver, heart, and other organ systems.

A primary characteristic of Alagille syndrome is liver damage stemming from bile duct abnormalities. Bile ducts are responsible for transporting bile, which aids in fat digestion, from the liver to the gallbladder and small intestine. In Alagille syndrome, these ducts can be abnormally narrow, misshapen, or reduced in number (a condition known as bile duct paucity). This leads to a buildup of bile in the liver, causing scarring and hindering the liver's ability to eliminate waste products from the bloodstream. Liver damage in Alagille syndrome can manifest as yellowing of the skin and eyes (jaundice), itchy skin, and cholesterol deposits in the skin (xanthomas).

Alagille syndrome is also linked to various heart problems, including restricted blood flow from the heart to the lungs (pulmonic stenosis). Pulmonic stenosis may occur alongside a hole between the heart's lower chambers (ventricular septal defect) and other heart anomalies. This combination of heart defects is known as tetralogy of Fallot.

Individuals with Alagille syndrome may exhibit distinct facial features, such as a wide, prominent forehead, deep-set eyes, and a small, pointed chin. The condition can also affect blood vessels in the brain and spinal cord (central nervous system) and the kidneys. Some individuals may have vertebrae (spinal bones) with an unusual butterfly shape, visible on an X-ray.

The problems associated with Alagille syndrome typically become apparent during infancy or early childhood. The severity of the condition varies widely among individuals, even within the same family. Symptoms can range from being so mild as to be unnoticed to severe heart and/or liver disease requiring transplantation.

Some individuals with Alagille syndrome may only exhibit isolated signs, such as a heart defect like tetralogy of Fallot or the characteristic facial appearance, without experiencing liver disease or other common features of the disorder.

Inheritance:

The inheritance pattern of this condition is autosomal dominant. This means that only one copy of the mutated or deleted gene in each cell is necessary to cause the disorder. Approximately 30% to 50% of affected individuals inherit the mutated gene from a parent who also has Alagille syndrome. In other cases, the condition arises from new gene mutations or deletions of genetic material on chromosome 20. These new mutations or deletions occur randomly during the formation of reproductive cells (eggs or sperm) or in early fetal development. These cases appear in people with no family history of Alagille syndrome.