Andersen-Tawil syndrome
Encyclopedia
Andersen–Tawil syndrome, also called Andersen syndrome and Long QT syndrome 7, is a form of long QT syndrome
. It is a rare genetic disorder, and is inherited in an autosomal dominant pattern.
, 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
.
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
. Mutation
s 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.
Long QT syndrome
The long QT syndrome is a rare inborn heart condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsade de pointes . These episodes may lead to palpitations, fainting and sudden death due to ventricular fibrillation...
. It is a rare genetic disorder, and is inherited in an autosomal dominant pattern.
Presentation
Andersen–Tawil syndrome affects the heartHeart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
, 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
Clinodactyly
-References:...
.
Type 1 and type 2
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 KCNJ2KCNJ2The Kir2.1 inward-rectifier potassium ion channel is encoded by the gene.- Clinical significance :A defect in this gene is associated with Andersen-Tawil syndrome.A mutation in the KCNJ2 gene has also been shown to cause short QT syndrome....
geneGeneA gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
- The remaining 40 percent of cases are designated as type 2; the cause of the condition in these cases is unknown.
The protein made by the KCNJ2 gene forms a channel
Potassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...
that transports potassium ions into muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
. 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
Cardiac muscle
Cardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
. Mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s 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.
Symptoms
- Widely spaced eyes (hypertelorismHypertelorismHypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits . In this condition the distance between the inner eye corners as well as the distance between the pupils is greater than normal...
) - Short stature
- Scoliosis
- Webbed toes or fingers
- Unusual short fingers
- Low set ears
- Broad forehead
- Small jaw
- Protruding jaw
- Broad nasal root
Clinical signs
- Prolongation of QT interval
- Cardiac arrhythmias
- Weakness: attacks or permanent