Titre : | Andersen-Tawil Syndrome : Synonym: Long QT Syndrome Type 7 (LQTS Type 7) |
Revue : | GeneReviews® [Internet] |
Auteurs : | Veerapandiyan A ; Statland JM ; Tawil R |
Type de document : | Article |
Année de publication : | 07/06/2018 |
Langues: | Anglais |
Mots-clés : | article de type review ; arythmie cardiaque ; cardiomyopathie dilatée ; conseil génétique ; corrélation génotype-phénotype ; diagnostic ; diagnostic différentiel ; électrocardiographie ; électrodiagnostic ; épilepsie ; faiblesse musculaire ; gène KCNJ2 ; génétique moléculaire ; malformation ; paralysie périodique ; pénétrance ; potassium ; prévention des complications ; prise en charge thérapeutique ; syndrome d'Andersen-Tawil ; tableau clinique ; trouble de l'apprentissage |
Résumé : |
Initial Posting: November 22, 2004; Last Update: June 7, 2018.
Clinical characteristics. Andersen-Tawil syndrome (ATS) is characterized by a triad of: episodic flaccid muscle weakness (i.e., periodic paralysis); ventricular arrhythmias and prolonged QT interval; and anomalies including low-set ears, widely spaced eyes, small mandible, fifth-digit clinodactyly, syndactyly, short stature, and scoliosis. Affected individuals present in the first or second decade with either cardiac symptoms (palpitations and/or syncope) or weakness that occurs spontaneously following prolonged rest or following rest after exertion. Mild permanent weakness is common. Mild learning difficulties and a distinct neurocognitive phenotype (i.e., deficits in executive function and abstract reasoning) have been described. Diagnosis/testing. The diagnosis of ATS is established in an individual with characteristic clinical and ECG findings and/or identification of a pathogenic variant in KCNJ2. Management. Treatment of manifestations: For episodic weakness: if serum potassium concentration is low (<3.0 mmol/L), administration of oral potassium (20-30 mEq/L) every 15-30 minutes (not to exceed 200 mEq in a 12-hour period) until the serum concentration normalizes; if a relative drop in serum potassium within the normal range causes episodic paralysis, an individual potassium replacement regimen with a goal of maintaining serum potassium levels in the high range of normal can be considered; if serum potassium concentration is high, ingesting carbohydrates may lower serum potassium levels. Mild exercise may shorten or reduce the severity of the attack. Prevention of primary manifestations: Reduction in frequency and severity of episodic attacks of weakness with lifestyle/dietary modification to avoid known triggers; use of carbonic anhydrase inhibitors; daily use of slow-release potassium supplements; implantable cardioverter-defibrillator for those with tachycardia-induced syncope. Empiric treatment with flecainide should be considered for significant, frequent ventricular arrhythmias in the setting of reduced left ventricular function. Prevention of secondary complications: Cautious use of antiarrhythmic drugs (particularly class I drugs) that may paradoxically exacerbate the neuromuscular symptoms. Surveillance: Annual screening of asymptomatic individuals with a KCNJ2 pathogenic variant with a 12-lead ECG and 24-hour Holter monitoring. Agents/circumstances to avoid: Medications known to prolong QT intervals; salbutamol inhalers (may exacerbate cardiac arrhythmias); thiazide and other potassium-wasting diuretics (may provoke drug-induced hypokalemia and could aggravate the QT interval prolongation). Evaluation of relatives at risk: Molecular genetic testing if the pathogenic variant is known; if not, detailed neurologic and cardiologic evaluation, 12-lead ECG, and 24-hour Holter monitoring to reduce morbidity and mortality through early diagnosis and treatment of at-risk relatives. Genetic counseling. ATS is inherited in an autosomal dominant manner. At least 50% of individuals diagnosed with ATS have an affected parent. Up to 50% of affected individuals have ATS as the result of a de novo pathogenic variant. Each child of an individual with ATS has a 50% chance of inheriting the disorder. Prenatal diagnosis for pregnancies at increased risk is possible if the KCNJ2 pathogenic variant has been identified in an affected family member. |
Lien associé : | Texte complet disponible en accès libre sur Bookshelf GeneReviews® |
Pubmed / DOI : | Pubmed : 20301441 |