Andersen-Tawil syndrome
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Andersen syndrome; long QT syndrome 7
Overview
Andersen-Tawil syndrome is a form of long QT syndrome. It is a rare genetic disorder, and is inherited in an autosomal dominant pattern.
Historical Perspective
It is named for Ellen Andersen[1]and R. Tawil.[2][3]
Classification
Two types of Andersen-Tawil syndrome are distinguished by their genetic causes.
- Type 1, which accounts for about 60 percent of all cases of the disorder, is caused by mutations in the KCNJ2 gene. [4][5]
- The remaining 40 percent of cases are designated as type 2; the cause of the condition in these cases is unknown.
Pathophysiology
Andersen-Tawil syndrome affects the heart, symptoms are a disruption in the rhythm of the heart's lower chambers (ventricular arrhythmia) in addition to the symptoms of long QT syndrome. There are also physical abnormalities associated with Andersen-Tawil syndrome, these typically affect the head, face, and limbs. These features often include an unusually small lower jaw (micrognathia), low-set ears, and an abnormal curvature of the fingers called clinodactyly.
Genetics
The protein made by the KCNJ2 gene forms a channel that transports potassium ions into muscle cells. The movement of potassium ions through these channels is critical for maintaining the normal functions of skeletal muscles which are used for movement and cardiac muscle. Mutations in the KCNJ2 gene alter the usual structure and function of potassium channels or prevent the channels from being inserted correctly into the cell membrane. Many mutations prevent a molecule called PIP2 from binding to the channels and effectively regulating their activity. These changes disrupt the flow of potassium ions in skeletal and cardiac muscle, leading to the periodic paralysis and irregular heart rhythm characteristic of Andersen-Tawil syndrome.
Researchers have not yet determined the role of the KCNJ2 gene in bone development, and it is not known how mutations in the gene lead to the developmental abnormalities often found in Andersen-Tawil syndrome.
References
- ↑ Andersen ED, Krasilnikoff PA, Overvad H (1971). "Intermittent muscular weakness, extrasystoles, and multiple developmental anomalies. A new syndrome?". Acta paediatrica Scandinavica. 60 (5): 559–64. PMID 4106724.
- ↑ Tawil R, Ptacek LJ, Pavlakis SG; et al. (1994). "Andersen's syndrome: potassium-sensitive periodic paralysis, ventricular ectopy, and dysmorphic features". Ann. Neurol. 35 (3): 326–30. doi:10.1002/ana.410350313. PMID 8080508.
- ↑ Template:WhoNamedIt
- ↑ Tristani-Firouzi M, Jensen JL, Donaldson MR; et al. (2002). "Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome)". J. Clin. Invest. 110 (3): 381–8. PMID 12163457.
- ↑ Pegan S, Arrabit C, Slesinger PA, Choe S (2006). "Andersen's syndrome mutation effects on the structure and assembly of the cytoplasmic domains of Kir2.1". Biochemistry. 45 (28): 8599–606. doi:10.1021/bi060653d. PMID 16834334.
Source
- This article incorporates public domain text from The U.S. National Library of Medicine