Synonyms and keywords: Autosomal Dominant Long QT syndrome, Long QT syndrome without deafness, LQTS, Romano-Ward Long QT syndrome, RWS, Ward-Romano syndrome, Romano-Ward syndrome
In 1990, LQTS 1, LQTS 2 and LQTS 3 the three main types of LQTS and their genes involved and proteins involved are identified for the first time.
Classification
LQT1-associated S3 mutants traffic to the plasma membrane in ltk− cells. (A) Western blot of WT and mutant KCNQ1+KCNE1proteins 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]
Mutations in any of these genes alter the structure or function of channels, which changes the flow of ions between cells and results in abnormal heart rhythm
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:[21][22]
Competitive sports, amusement park rides, frightening movies, jumping into cold water etc
Based on the genotype the triggering events may differ, for example:[23]
In patients with LQT1genotype exercise or swimming is the trigger for cardiac events due to stimulation of vasovagal reflex
In patients with LQT2genotype emotions, exposure to auditory stimuli like door bells, telephone ring can trigger the cardiac events
In patients with LQT3genotype 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
Common complications of Romano-Ward syndrome include:
The prognosis varies with the type of genes and mutations involved in the pathogenesis of the Romano-Ward syndrome patients. However, the prognosis is generally range from poor to good
Diagnosis
Diagnostic study of choice
Along with clinical features and molecular genetic testing is the gold standard test for the diagnosis of Romano-Ward syndrome which includes single-gene testing, use of a multigene testing panel, and more comprehensive genomictesting.
The following result of moleculargenetic testing is confirmatory of Jervell and Lange-Nielsen syndrome (JLNS):
Cardiovascular examination of patients with Romano-Ward syndrome should be done to rule out other causes of arrhythmic and syncopal events which include the diseases like heart murmurs caused by hypertrophic cardiomyopathy, valvular defects
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[26]
Laboratory Findings
There are no diagnostic laboratory findings associated with Romano-Ward syndrome.
Laboratory findings that should be considered and checked routinely in Romano-Ward syndrome include:
Serum potassium levels
Serum magnesium levels
Electrocardiogram
Romano-Ward syndrome with the broad-based T pattern. Case courtesy by G. Michael Vincent, MD[27]An ECG may be helpful in the diagnosis of Romano-Ward syndrome. Findings on an ECGdiagnostic of Romano-Ward syndrome include the following:[28][29][30][31][32]
Prolongation of the QTc interval greater than 500 msec
In cardiac muscle, these ion channels play critical roles in maintaining the heart's normal rhythm. Mutations in any of these genes alter the structure or function of channels, which changes the flow of ions between cells.
A disruption in ion transport alters the way the heartbeats, leading to the abnormal heart rhythm characteristic of Romano-Ward syndrome.
Unlike most genes related to Romano-Ward syndrome, the ANK2 gene does not produce an ion channel. The protein made by the ANK2 gene ensures that 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 and results in the features of Romano-Ward syndrome.