Romano-Ward Syndrome

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What is Romano-Ward syndrome?

Romano-Ward syndrome is a condition that causes a disruption of the heart's normal rhythm (arrhythmia). This disorder is a form of long QT syndrome, which is a heart condition that causes the heart (cardiac) muscle to take longer than usual to recharge between beats. The irregular heartbeats can lead to fainting (syncope) or cardiac arrest and sudden death.

How common is Romano-Ward syndrome?

Romano-Ward syndrome is the most common form of inherited long QT syndrome, affecting an estimated 1 in 7,000 people worldwide. The disorder may actually be more common than this estimate, however, because some people never experience any symptoms associated with arrhythmia and therefore may not have been diagnosed.

What genes are related to Romano-Ward syndrome?

Mutations in the KCNE1, KCNE2, KCNH2, KCNQ1, and SCN5A genes cause Romano-Ward syndrome.

The ANK2 gene is associated with Romano-Ward syndrome.

The KCNE1, KCNE2, KCNH2, KCNQ1, and SCN5A genes provide instructions for making proteins that act as channels across the cell membrane. These channels transport positively charged atoms (ions), such as potassium and sodium, into and out of cells. In cardiac muscle, ion channels play critical roles in maintaining the heart's normal rhythm. Mutations in any of these genes alter the structure or function of these channels, which changes the flow of ions between cells. A disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of Romano-Ward syndrome.

Unlike most genes related to Romano-Ward syndrome, the ANK2 gene does not provide instructions for making an ion channel. The ANK2 protein, ankyrin-2, ensures that certain other proteins (particularly ion channels) are inserted into the cell membrane appropriately. A mutation in the ANK2 gene likely alters the flow of ions between cells in the heart, which disrupts the heart's normal rhythm. ANK2 mutations can cause a variety of heart problems, including the irregular heartbeat often found in Romano-Ward syndrome. It is unclear whether mutations in the ANK2 gene cause Romano-Ward syndrome or lead to another heart condition with some of the same signs and symptoms.

How do people inherit Romano-Ward syndrome?

This condition is typically inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. A small percentage of cases result from new mutations in one of the genes described above. These cases occur in people with no history of Romano-Ward syndrome in their family.

Source: National Institutes of Health

Research from University of Foggia, Cardiology Department broadens understanding of long QT syndrome genetics

"Previous studies have demonstrated locus heterogeneity, with causative mutations reported in >or=8 different genes, including the human ether-a-go-go-related gene. This study was conducted in 26 members of a 4-generation family with long-QT syndrome. The proband was a 14-year-old female patient referred to the emergency department for the evaluation of recurrent syncope associated with a prolonged QT interval on electrocardiography at rest. There was a family history of sudden death in a 27-year-old woman. Sequencing of the entire coding regions of the human ether-a-go-go-related gene and the intron and exon boundaries of the proband identified a single base-pair substitution (guanine to cytosine at nucleotide 1468). This mutation resulted in a novel missense mutation, alanine to proline at position 490 (Ala490Pro), in the inner loop of the S2 and S3 domains. The proband was heterozygous for the Ala490Pro mutation. To address whether the mutational change detected in the patient would be a polymorphism, 100 control subjects from the same ethnical background were investigated. None showed the Ala490Pro substitution. Of 26 family members, 9 were mutation carriers, and none had normal electrocardiographic results. The penetrance of this pedigree was assumed to be 100%," wrote P.L. Pellegrino and colleagues, University of Foggia, Cardiology Department.

The researchers concluded: "The Ala490Pro mutation of the human ether-a-go-go-related gene is a rare, novel mutation that was inherited in this family, leading to Romano-Ward syndrome with complete penetrance."

Pellegrino and colleagues published their study in American Journal of Cardiology (A novel mutation in human ether-a-go-go-related gene, alanine to proline at position 490, found in a large family with autosomal dominant long QT syndrome. American Journal of Cardiology, 2007;99(12):1737-40).

For additional information, contact P.L. Pellegrino, University of Foggia, Cardiology Department, Foggia, Italy.

The publisher of the American Journal of Cardiology can be contacted at: Excerpta Medica Inc., 650 Avenue of the Americas, New York, NY 10011, USA.

Keywords: Italy, Foggia, Long QT Syndrome Genetics, Cardiology, Long QT Syndrome.

This article was prepared by Cardiovascular Week editors from staff and other reports. Copyright 2007, Cardiovascular Week via NewsRx.com.