Management and Treatment of Andersen-Tawil Syndrome (ATS)

Abstract

Summary: Andersen-Tawil syndrome (ATS) is characterized by periodic paralysis, cardiac arrhythmias, and distinct facial and skeletal features. The majority of patients with ATS (ATS1) have point mutations in the KCNJ2 gene, which encodes the inward-rectifying potassium channel known as Kir2.1. The skeletal muscle and cardiac symptoms are accounted for, in most cases, by a dominant negative effect of the mutations on potassium channel current, resulting in prolonged depolarization of the action potential. Mechanisms of disruption of channel function include abnormal trafficking and assembly of second messengers such as phosphatidylinositol 4,5-bisphosphate, abnormal gating of the channel, and incorrect folding of the Kir2.1 protein. Less apparent is the mechanism by which these mutations account for the typical facial and skeletal abnormalities. The concomitant involvement of cardiac and skeletal muscle in ATS poses unique treatment and management challenges. Because of differences in cardiac and skeletal muscle physiology, drugs that may have a beneficial effect on cardiac function may have a detrimental effect on skeletal muscle and vice versa. We review the clinical, laboratory, and genetic features of this disorder with particular emphasis on treatment and management.

A novel neuropsychiatric phenotype of KCNJ2 mutation in one Taiwanese family with Andersen–Tawil syndrome

“…3 It is noted that there is one similar case reported in the previous literature that multiple white matter hyperintense lesions were found in a 24-year-old woman with ATS caused by the KCNJ2 mutation, who also had diffuse pyramidal signs. 10 Consistent with our neuropsychiatric findings, one recent study that performed neuropsychological tests on ten ATS patients from eight unrelated families showed that cognitive dysfunctions, including defects in executive functions and abstract reasoning, could be part of the ATS clinical spectrums. 4 Combined with our observations, these findings suggest that the neuropsychiatric phenotypes of ATS may be largely underestimated by clinicians and further large sample studies are warranted to clarify the detail of the CNS involvement in ATS.…”

Child Neurology: Andersen-Tawil syndrome

“…2 Patients may develop fainting spells or, in some cases, present with cardiac arrest leading to sudden death. ATS is also classified as "long QT syndrome type 7" (LQTS7), although the QT interval is either normal or only slightly prolonged in most cases.…”

“…2 Dysmorphisms include broad forehead, hypoplastic mandible, hypotelorism, short palpebral fissures, short nose with fullness along the bridge and bulbous tip, thin upper lip, high arched or cleft palate, triangular facies, digit clinodactyly, syndactyly of the 2nd and 3rd toes, and short stature. 2,8 Patients with ATS have a distinct neurocognitive phenotype characterized by deficits in executive function and abstract reasoning. 9 ATS is a syndrome with a very high degree of phenotypic variability and is therefore very difficult to diagnose.…”

“…2 Hypokalemic paralysis is associated with low serum potassium levels, whereas patients with hyperkalemic periodic paralysis generally have increased levels of serum potassium. In patients with ATS, periodic paralysis can occur with normokalemia, hyperkalemia, or hypokalemia.…”

Congenital long QT syndrome in children

“…Jervell and Lange-Nielsen (JLN) syndrome is a rare autosomal recessive (A-R) disease caused by homozygous mutation in KCNQ1, associated with congenital deafness and very severe form of LQTS (12). Andersen-Tawil syndrome, known as LQT7, is a rare A-D condition characterized by hypokalemic periodic paralysis, ventricular tachyarrhythmias and a variety of dysmorphic features (13). Tymothy syndrome (LQT8) is the consequence of CACNA1c gene mutation, manifested with LQTS, facial dysmorphia, syndactilia and neurocognitive insufficiency (14).…”