Romano Ward Syndrome

Romano Ward Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Romano Ward Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Long QT Syndrome without Deafness
  • Autosomal Dominant Long QT Syndrome
  • Long QT Syndrome Type 1
  • LQTS1
  • RWS
  • Romano-Ward Long QT Syndrome
  • Ward-Romano Syndrome

Disorder Subdivisions

  • None

General Discussion

Romano-Ward syndrome is an inherited heart (cardiac) disorder characterized by abnormalities affecting the electrical system of the heart. The severity of Romano-Ward syndrome varies greatly from case to case. Some individuals may have no apparent symptoms (asymptomatic); others may develop abnormally increased heartbeats (tachyarrhythmias) resulting in episodes of unconsciousness (syncope), cardiac arrest, and potentially sudden death. Romano-Ward syndrome is inherited as an autosomal dominant trait.

Symptoms

In many cases, the first symptom of Romano-Ward syndrome is partial or total loss of consciousness (syncope) accompanied by abnormally fast heart rhythms known as polymorphic ventricular tachycardia (VT) or torsade de pointes (TdPs). TdPs may progress to a more serious condition known as ventricular fibrillation (VF) in which the heart's normal electrical activity becomes disordered resulting in uncoordinated heartbeats and malfunction of the main pumping chambers of the heart (ventricles). Consequently, little or no blood is pumped from the heart. Ventricular fibrillation potentially results in cardiac arrest or sudden death.



Symptoms of Romano-Ward syndrome such as syncope tend to occur without warning and to recur unexpectedly. Overexertion, excitement or stress may trigger these recurrent symptoms, although they often begin without any precipitating factors. In some cases, episodes may be triggered by "startle" events such as an alarm clock going off or the phone ringing in the middle of the night. In some cases, events occur while the affected person is swimming. The severity and frequency of attacks vary. Some people may have mild chest pain with no loss of consciousness; others may lose consciousness completely or have grand mal seizures followed by a period of disorientation. In some cases, seizures may be the first apparent symptom of Romano-Ward syndrome. The severity and frequency of episodes often decrease during middle age.



Additional symptoms have occurred in some individuals with Romano-Ward syndrome including webbing of the fingers or toes (syndactyly), asthma, and diabetes mellitus.

Causes

Romano-Ward syndrome is inherited as an autosomal dominant trait. In rare cases, Romano-Ward syndrome occurs randomly as the result of a spontaneous genetic change (i.e., new mutation). These mutations are then passed on (inherited) as an autosomal dominant trait.



Genetic diseases are determined by two genes, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the 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 regardless of the sex of the resulting child.



Romano-Ward syndrome has been shown to be caused by disruptions or changes (mutations) in one of at least six different genes: KCNQ1, KCNH2 (HERG; LQT2), SCN5A (LQT3), KCNE1 (LQT1), (LQT5; mink), KCNE2 (LQT6; MiRP1). Recently, the LQT4 gene was identified as ankyrin B. These genes produce (encode) specific protein structures (ion channels) found in heart cells. Ion channels regulate the movement of electrically charged particles (e.g., potassium and sodium ions) across heart cell membranes. These ions transmit electrical signals needed for normal function of the heart. Mutations of these genes result in abnormal function of the ion channels and, in turn, improper function of the heart's electrical system. More than 200 different mutations of the seven identified genes have been reported.



Investigators have determined that the KCNQ1 (LQT1, previously called KvLQT1) gene is located on the short arm (p) of chromosome 11 (11p15.5). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 11p15.5" refers to band 15 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.



The KCNH2 gene is located on the long arm (q) of chromosome 7 (7q35-q36. The SCN5A gene is located on the short arm of chromosome 3 (3p21). The KCNE1 gene is located on the long arm of chromosome 21 (21q22.1-q22.2). The KCNE2 gene is located on the long arm of chromosome 21 (21q22.1), while ankyrin B is localized. Mutations of an unidentified gene are located on chromosome 4 (4q).



Romano-Ward syndrome is characterized by an abnormal electrocardiogram that demonstrates a prolonged QT interval and abnormal T wave morphology. The functioning of the heart is controlled by electrical nerve impulses that regulate normal rhythmic pumping activity of the heart muscle. After each heartbeat, this electrical system recharges, a process known as repolarization. During electrical stimulation, the heart muscle contracts, a process known as depolarization. The QT interval measures the amount of time required for these two processes to occur. When the QT interval is longer than normal (prolonged), the heartbeat may become irregular. Hence, this is a disease of repolarization.

Affected Populations

Romano-Ward syndrome affects males and females in equal numbers. The disorder is estimated to occur in 1 in 10,000 live births. However, because cases of Romano-Ward syndrome often go unrecognized, the disorder is under-diagnosed, making it difficult to determine its true frequency in the general population.



Symptoms of Romano-Ward syndrome usually become apparent during childhood, but may occur at any age.

Standard Therapies

Diagnosis

A diagnosis of Romano-Ward syndrome is made based upon a thorough clinical evaluation, a detailed patient history and a specialized test called an electrocardiogram (ECG or EKG). Individuals with unexplained history of fainting, syncope or sudden cardiac arrest should be evaluated for Romano-Ward syndrome. An electrocardiogram records the heart's electrical impulses and may reveal abnormal electrical patterns such as a prolonged QT interval characteristic of individuals with Romano-Ward syndrome. In some cases, blood samples can be tested for the presence of specific genetic mutations. However, this testing is not clinically available at present.



The absence of congenital deafness differentiates Romano-Ward syndrome from Jervell and Lange-Nielsen syndrome. Family members of individuals with Romano-Ward syndrome should be tested symptoms (e.g., prolonged QT interval) characteristic of the disorder.



Treatment

The treatment of individuals with Romano-Ward syndrome is aimed at preventing characteristic symptoms such as loss of consciousness or cardiac arrest. Specific medications, avoidance of triggering events, and certain medical devices may all be used to treat individuals with Romano-Ward syndrome.



The treatment of choice for most individuals with Romano-Ward syndrome is drug therapy with beta-adrenergic blocking agents (beta blockers). Beta blockers, which include propranolol, atenolol, and nadolol, reduce the workload of the heart by decreasing the electrical stimulation of the heart. Children and adults with Romano-Ward syndrome who do not have any apparent symptoms (asymptomatic) may receive preventative (prophylactic) treatment with beta blockers.



Individuals for whom beta blockers are unsuccessful may be treated by a surgical procedure in which certain nerves going to the heart are removed (left cardiac sympathetic denervation or sympathectomy). However, recently treatment with an implantable automatic cardioverter-defibrillator (ICD) has replaced sympathectomy as the treatment of choice in these individuals. This device detects the abnormal heartbeat automatically and selectively delivers an electrical impulse to the heart. ICDs are used in conjunction with antiarrythmic drug therapy.



Some individuals with Romano-Ward syndrome are encouraged to avoid potential triggering events such as jumping into cold water, amusement park rides or competitive sports. Genetic counseling may be of benefit for affected individuals and their families. Other treatments are symptomatic and supportive.

Investigational Therapies

An implantable device, the QT-sensitive cybernetic pacemaker, is also being tested for individuals with high-risk Romano-Ward syndrome. This unit may be able to monitor heart rhythm and detect development of severe heart beat irregularities. Effectiveness and side effects of these implanted devices have not been fully documented and more extensive research is being pursued before their therapeutic value for Romano-Ward syndrome can be evaluated.



Drugs that block the effects of sodium channels (e.g., mexilitine, lidocaine, and flecainide) are being tested in individuals with the LQT3 (SCN5A mutations) form of Romano-Ward syndrome. Drugs that increase serum potassium are also being studied in those with mutations in potassium channel genes (KCNQ1, KCNH2). More research is necessary to determine the long-term safety and effectiveness of these potential treatments for individuals with Romano-Ward syndrome.



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:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Towbin JA. Romano-Ward Long QT Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:54.



Towbin JA. Jervell and Lange-Nielsen Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:51-52.



Braunwald E, ed. Heart Disease. A Textbook of Cardiovascular Medicine. 3rd ed. Philadelphia, PA: W. B. Saunders Company; 1988:749, 1635.



REVIEW ARTICLES

Herbert E, et al. KCNQ1 gene mutations and the respective genotype-phenotype correlations in the long QT syndrome. Med Sci Monit. 2002;8:240-48.



Bloise R, et al. Romano-Ward syndrome and other congenital long QT syndromes. Cardiovasc Drugs Ther. 2002;16:19-23.



Towbin JA. Vatta M, Molecular biology and the prolonged QT syndromes. Am J Med. 2001;110:385-98.



Chiang CE, Roden DM. The long QT syndromes: genetic basis and clinical implications. J Am Coll Cardiol. 2000;36:1-12.



Wattanasirichaigoon D, Beggs AH. Molecular genetics of long-QT syndrome. Curr Opin Pediatr. 1998;10:628-34.



Ackerman MJ. The long QT syndrome: ion channel diseases of the heart. Mayo Clin Proc. 1998;73:250-69.



JOURNAL ARTICLES

Puddu PE, et al. The QT-sensitive cybernetic pacemaker: a new role for an old parameter? Pace. 1986,9:108-23.



Meschi V, et al. Prolonged Q-T syndrome (Romano-Ward syndrome). Description of a case diagnosed in infancy. Pediatr Med Chir. 1985;7:131-6.



Platia EV, et al. Management of the prolonged QT syndrome and recurrent ventricular fibrillation with an implantable automatic cardioverterdefibrillator. Clin Cardiol. 1985;8:490-93.



FROM THE INTERNET

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:192500; Last Update:6/3/03.



Zareba W, Rosero S. Long QT Syndrome. eMedicine Journal. 2002;3:11pp. Available at http://www.emedicine.com.



Vincent MG. Updated:6/16/2003. Romano-Ward Syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2003. Available at http://www.genetests.org.

Resources

International Long QT Syndrome Registry

Heart Research Follow-up Program

Box 653

University of Rochester Medical Center

Rochester, NY 14642-8653

Tel: (585)276-0016

Fax: (585)273-5283

Email: heartajm@heart.rochester.edu



American Heart Association

7272 Greenville Avenue

Dallas, TX 75231

Tel: (214)784-7212

Fax: (214)784-1307

Tel: (800)242-8721

Email: Review.personal.info@heart.org

Internet: http://www.heart.org



Sudden Arrhythmia Death Syndromes Foundation

508 E. South Temple

Suite 202

Salt Lake City, UT 84102

USA

Tel: (801)531-0937

Fax: (801)531-0945

Tel: (800)786-7723

Email: laura@sads.org

Internet: http://www.sads.org



NIH/National Heart, Lung and Blood Institute

P.O. Box 30105

Bethesda, MD 20892-0105

Tel: (301)592-8573

Fax: (301)251-1223

Email: nhlbiinfo@rover.nhlbi.nih.gov

Internet: http://www.nhlbi.nih.gov/



QTsyndrome.ch

Ronnerweg 2

Nidau, 2560

Switzerland

Tel: 0041794741535

Email: info@qtsyndrome.ch

Internet: http://www.qtsyndrome.ch/index.html



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use . How this information was developed to help you make better health decisions.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.