Clinical Guidance

Whether a KCNJ2 pathogenic variant is present or not, individuals with clinically defined ATS are phenotypically indistinguishable . In a case series that evaluated for KCNJ2 pathogenic variants in individuals with typical (2 ATS features) and atypical (only 1 ATS feature or catecholaminergic polymorphic ventricular tachycardia [CPVT]) features of ATS, the proportion of individuals with an identified pathogenic variant was 75% (15/20) in those with typical ATS, 71% (5/7) in those with the cardiac phenotype alone, 100% (2/2) in those with periodic paralysis, and 7% (2/28) in those with CPVT . In a single large kindred with the KCNJ2 pathogenic variant, periodic paralysis was observed only in men, cardiac symptoms only in women, and congenital anomalies in both .

Source: GeneReviews — "Andersen-Tawil Syndrome"

Penetrance

Non-penetrance is evident in 6%-20% of individuals with an identifiable pathogenic variant .

Source: GeneReviews — "Andersen-Tawil Syndrome"

Diagnostic Criteria

Suggestive Findings

Andersen-Tawil syndrome (ATS) should be suspected in individuals with either A or B: A. Presence of two of the following three criteria:

• Periodic paralysis

• Symptomatic cardiac arrhythmias or electrocardiographic evidence of enlarged U-waves, ventricular ectopy, or a prolonged QTc or QUc interval

• Characteristic facies, dental anomalies, small hands and feet, AND at least two of the following:

• Low-set ears

• Widely spaced eyes

• Small mandible

• Fifth-digit clinodactyly

• Syndactyly of toes 2 and 3

B. One of the above three criteria AND at least one other family member who meets two of the three criteria

Supportive Findings

Individuals with either episodic weakness or cardiac symptoms require careful evaluation by a neurologist and/or cardiologist as well as measurement of serum potas...

Source: GeneReviews — "Andersen-Tawil Syndrome"

Differential Diagnosis

Andersen-Tawil syndrome (ATS) should be considered in any individual presenting with periodic paralysis and ventricular arrhythmias or prominent U wave or prolonged QTc. Individuals with either episodic weakness or cardiac symptoms require careful evaluation by a neurologist and/or cardiologist as well as measurement of serum potassium concentration (baseline and during attacks of flaccid paralysis), a 12-lead EKG, a 24-hour Holter monitor, and possibly the long exercise protocol. The differential diagnosis depends on the initial presentation and includes the primary and secondary periodic paralyses, thyrotoxic periodic paralysis, and conditions associated with long QT.

Episodes of Flaccid Paralysis

Hypokalemic periodic paralysis is the most common periodic paralysis. Affected individuals ma...

Source: GeneReviews — "Andersen-Tawil Syndrome"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Andersen-Tawil syndrome (ATS), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 2. Recommended Evaluations Following Initial Diagnosis in Individuals with ATS

Source: GeneReviews — "Andersen-Tawil Syndrome"

Clinical Guidance

Affected individuals should avoid medications known to prolong QT intervals. See CredibleMeds® for a complete and updated list (free registration required). Salbutamol inhalers, which may be used in the treatment of primary hyperkalemic periodic paralysis, should be avoided because of the potential for exacerbation of cardiac arrhythmias. Thiazide and other potassium-wasting diuretics may provoke drug-induced hypokalemia and could aggravate the QT interval prolongation.

Source: GeneReviews — "Andersen-Tawil Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Andersen-Tawil Syndrome"

Surveillance Guidelines

For asymptomatic individuals with a KCNJ2 pathogenic variant, annual screening including a 12-lead EKG and 24-hour Holter monitoring is desirable, followed by referral to a cardiologist if abnormalities are identified.

Source: GeneReviews — "Andersen-Tawil Syndrome"