Romano-Ward syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Synonyms and keywords: Autosomal dominant long QT syndrome; long QT syndrome without deafness; romano-ward long QT syndrome; ward-romano syndrome; romano-ward syndrome; LQTS; RWS

Overview

Romano-Ward syndrome is a rare congenital genetic condition with autosomal dominant inheritance pattern which leads to abnormal ventricular myocardial repolarization which results in long QT syndrome (LQTS). Among all other long QT syndrome (LQTS) Romano-Ward syndrome is the most common one. Romano-Ward syndrome is due to mutation in LQT1, LQT2 and LQT3 genes. Romano-Ward syndrome has a purely cardiac phenotype of QT prolongation in contrast to Jervell and Lange-Nielsen syndrome which has both sensorineural deafness and cardiac events.

Historical Perspective

Classification

  • LQT1-associated S3 mutants traffic to the plasma membrane in ltk− cells. (A) Western blot of WT and mutant KCNQ1+KCNE1 proteins expressed in ltk− cells, untreated and treated with proteinase K (PK) to distinguish surface-expressed channel from internal. After normalization to actin for control of loading, the percent surface protein was determined from the density of bands before and after proteinase K treatment (n = 3) and was found to be: WT, 73%; D202H, 91%; D202N, 80%; I204F, 80%; I204M, 90%; V205M, 75%; S209F, 82%; V215M, 75%. (B) Model of KCNQ1 tetrameric channels showing the locations of S3 mutations in space fill from the side and the extracellular face, with each subunit a different color. Case courtesy by Jodene Eldstrom et al[8]
    The Long QT syndrome (LQTS) may be classified into several subtypes:[9][10][11][12][13]


LQT Gene Involved Chromosome involved Protein Involved Ion channel Involved
LQT 1 KCNQ1 11p15.5 Iks a subunit Iks
LQT 2 HERG 7q35-36 Ikr a subunit Ikr
LQT 3 SCN5A 3q21-24 Sodium channel INa
LQT 4 NOT KNOWN 4q25-27 Unknown Unknown
LQT 5 KCNE1 21q22.1-2 Iks a subunit Iks
LQT 6 KCNE2 21q22.1 Ikr b subunit Ikr

Pathophysiology

Causes

Genetic Causes

Differentiating Romano-Ward syndrome from other Diseases

Romano-Ward syndrome must be differentiated from Jervell and Lange-Nielsen syndrome (JLNS), Timothy syndrome, Andersen-Tawil syndrome, Brugada syndrome, and Sudden infant death syndrome (SIDS).[20][21][22][23][24][25][26][27]

Epidemiology and Demographics

Incidence

  • The incidence of Romano-Ward syndrome is approximately 1 in 2,000 people worldwide individuals worldwide.

Prevalence

  • The prevalence of Romano-Ward syndrome is approximately 1:20 000 to 1:5000 individuals worldwide.[28]
  • The prevalence of Romano-Ward syndrome is approximately 1 in 2000 live births.

Race

  • There is no racial predilection to Romano-Ward syndrome.

Gender

  • Romano-Ward syndrome affects men and women equally.

Risk Factors

  • Apart from the genetic mutations in ANK2, KCNE1, KCNE2, KCNH2, KCNQ1, and SCN5A genes, there are some risk factors associated with Romano-Ward syndrome.
  • Other common risk factors in the development of Romano-Ward syndrome symptoms include sudden sleep arousal, exercise and intense or sudden emotion which include the following:[29][30]
    • Competitive sports, amusement park rides, frightening movies, jumping into cold water etc
  • Based on the genotype the triggering events may differ, for example:[31]
    • In patients with LQT1 genotype exercise or swimming is the trigger for cardiac events due to stimulation of vasovagal reflex
    • In patients with LQT2 genotype emotions, exposure to auditory stimuli like door bells, telephone ring can trigger the cardiac events
    • In patients with LQT3 genotype cardiac events can be triggered during sleep

Screening

  • There is insufficient evidence to recommend routine screening for Romano-Ward syndrome.

Natural History, Complications and Prognosis

Natural History

  • The symptoms of Romano-Ward syndrome usually develop in the second decade of life, and start with symptoms such as syncope and palpitations.
  • The symptoms of Romano-Ward syndrome typically decreases with increase in the age, after the age of 40 years the symptoms are less common than usual.

Complications

Prognosis

Diagnosis

Diagnostic study of choice

History and Symptoms

Common Symptoms

Common symptoms of Romano-Ward syndrome include:[33][34]

Less Common Symptoms

Less common symptoms of Romano-Ward syndrome include

Physical Examination

Vital Signs

Heart



Romano-Ward syndrome
LQT1 patient ECG showing a normal T wave pattern and average QTc of about more than 480 msec. Case courtesy by G. Michael Vincent, MD[35]

Laboratory Findings

  • There are no diagnostic laboratory findings associated with Romano-Ward syndrome.

Electrocardiogram

X-Ray

LQTS
Representative electrocardiograms (ECG) from members of a family with LQTS. Top, ECG from a normal family member (I-1); Middle, ECG from a heterozygous mutation carrier; Bottom, ECG from a homozygous mutation carrier.[44]
  • There are no x-ray findings associated with Romano-Ward syndrome.

Ultrasound

MRI

Treatment

Medical Therapy

Acute Management of Torsades de pointes

Interventions

Surgery

Primary Prevention

Secondary Prevention


Template:WikiDoc Sources

References

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