Andersen's syndrome – the rare hereditary pathology which is characterized by the extended interval of QT and vysokoapmlitudny teeth of U on the ECG, ventricular arrhythmia, attacks of muscular paralysis, existence of external signs of a dismorfogenez. At patients low put ears, a wide forehead, abnormally increased jaw, steady deformation of fingers decide on an union and membranes, the increased distance between eyes, the low growth, scoliosis. The diagnosis is established on the basis of clinical yielded, results of a genetic research and the ECG. Treatment is symptomatic, includes reception of antagonists of calcium and β-adrenoblokator, restriction of physical activities.
In 1971 the Danish doctor E. Andersen described symptoms of a dismorfogenez, ventricular arrhythmia and attacks of paralysis at the boy of 8 years. In 1994 the neurologist R. Tavil investigated a clinical picture of a disease in more detail, differentiated passing paralysis at this disease from other forms of periodic paralysis. In the works he for the first time used the term "Andersen's syndrome". Now also other name – Andersen-Tavila's syndrome is distributed. The epidemiology is extremely low: 1 case of a disease on 1 million newborns is diagnosed. Incidence is identical among girls and boys, and also among different races and ethnogroups. Andersen's syndrome should be distinguished with Andersen's disease – a hereditary disease of accumulation of a glycogen in bodies and fabrics.
In 2001 the genetic basis of a syndrome of Andersen was defined: when studying clinical cases in a family of 15 people scientists found communication between inheritance of a disease and existence of heterozygotic mutations in the KCNJ2 gene located in 17q a locus 23 chromosomes. This gene is responsible for synthesis alpha a squirrel of Kir2.1 in the entering potassium canals warm and skeletal muscles.
Hereditary transfer of a syndrome happens on the autosomno-prepotent mechanism, at the same time isolated sporadic cases – spontaneous primary mutational change of a gene during conception are revealed. At autosomno-prepotent inheritance the probability of the birth of the sick child in couple where one of parents has a defective gene, makes 50%. The Penetrantnost of a disease is widely variable therefore not all patients have the developed symptomatology. Severity of pathology varies within a family: at one patients it is shown by the expressed cardiological and miopatichesky violations, at others proceeds asimptomno.
Pathogenetic basis of a syndrome of Andersen is insufficiency of production of the proteinaceous molecules Kir2.1. They are included into structure of potassium channels of the cages capable to excitability – kardiomiotsit, neurons of a brain, cells of cross-striped muscles. Potassium channels regulate the membrane potential of rest of skeletal muscles and cardiac muscle. At their dysfunction excitability of fabrics pathologically changes: an exit of ions of K+ from the cages having a giperpolyarizirovanny membrane in a final phase of repolarization of potential is broken.
The transcriptions of a gene of KCNJ2 containing a large number of Kir2.1 are found in heart tissues (especially in auricles and ventricles), a brain, a placenta, muscles of a skeleton, lungs. α-subjedinitsa of Kir2.1 form tetrameasures in cellular walls, form the potassium channel. At Andersen's syndrome the insufficient quantity of these subjedinitsa is synthesized. Depolarization and destabilization of membrane potential of rest results, ventricular arrhythmias, muscular contractions, paralyzes develop.
The full clinical picture of a syndrome of Andersen is presented by the triad of symptoms including potassium - dependent periodic paralyzes, ventricular violations of a rhythm, anomaly of a structure of a skull and extremities. At easy forms of a disease passing muscular paralyzes are felt as weakness attacks, short on time, in legs and hands. The moderate and heavy current of a syndrome is followed by full or partial paralysis of extremities, generalized paresis with loss of sensitivity, a possibility of any movements. These episodes often arise after intensive physical activity or morning awakening, suddenly in a condition of slackness and rest. Refer foot walk to triggers of paralysis on an empty stomach, plentiful meal, physical activity after the sitting period, catarrhal diseases, inhalation of toxic gases.
Arrhythmias are the most common symptom of a disease. At a part of patients they come to light only at the ECG. The feeling of heartbeat and interruptions of a warm rhythm, increase ChSS, discomfort and breast pains, dizziness, loss of consciousness and feeling close to a faint can subjectively be noted. Signs of a dismorfogenez are presented by low growth; a makrotsefaliya – increase in the size of a skull by 10% and more from standard of age; a dolikhotsefaliya – lengthening of a skull in the perednezadny direction because of prematurity of ossification of an arrow-shaped seam. Also the gipertelorizm – a wide arrangement of pair bodies, for example, of eyes is observed. The ears which are low put and rotirovanny back. At some patients the epikant – a fold at an internal corner of an eye is created. A hard and soft palate often remain nezarashchenny, the top jaw has the small amount (mikrognatiya), fingers are abnormally shortened (brakhidaktiliya), the fifth fingers lateralno and medially bent (klinodaktiliya). The union of fingers and existence of membranes is sometimes observed.
Development of zhizneugrozhayushchy states is possible at patients with severe forms of a disease, especially if there is no necessary treatment and leaving. Frequent attacks of paralysis are followed by risk of injuries: patients suddenly lose control over a tone of muscles, fall, get bruises and injuries. Especially dangerous such states are when driving transport, crossing the street etc. In the absence of therapeutic control of ventricular arrhythmia there is a small probability of sudden death as a result of cardiac arrest. In scientific literature several cases of similar lethal outcomes are described.
Symptoms of pathology can be revealed on the first year of life of the child. Pediatricians pay attention to defects of formation of fingers of hands and legs, skulls, especially its front part. At easy option of a disease external signs are poorly expressed or are absent, then the diagnosis is defined later, after casual detection of changes of a rhythm of heart. Examination of patients is conducted by cardiologists, neurologists, geneticists. Differential diagnostics is directed to an exception of other types of arrhythmias. The following procedures allow to confirm existence of a syndrome of Andersen:
- Kliniko-anamnestichesky research. The family anamnesis gathers, are carried out the genealogical analysis. Most of patients has close relatives with the confirmed diagnosis of a syndrome. At survey characteristic craniofacial anomalies, changes of a structure of fingers are registered. At poll complaints to attacks of muscular weakness or paralysis, discomfort in a breast, uneven heartbeat are possible.
- ECG. According to an electrocardiography lengthening of an interval of QT is defined: an average value women – 479 ms, at men have 493 ms. Other diagnostic criterion – the high amplitude of teeth of U which is registered mainly in forward chest assignments. U teeth expanded and two-phase, the descending part of teeth of T is prolonged, merge of T-U wide. Sinkopalny episodes are followed by piruetny ventricular tachycardia.
- Genetic research. Blood test from a vein is carried out. The structure of a gene responsible for development of a disease (KCNJ2) is studied. Approximately mutations in a heterozygotic and kompanud-heterozygotic state are found in 70-80% of patients. The type of a mutation is individual. The heterozygotic missens-mutation of R218W is considered the most widespread.
Treatment of a syndrome of Andersen
Etiotprony treatment is not developed, attempts of application of high doses of medicines of potassium are inefficient. The main method of therapy is appointment beta and blockers of calcic channels (fenilalkilamin). These medicines reduce displays of arrhythmia, reducing force and heart rate, oppressing warm conductivity. At a heavy current of a syndrome with sinkopalny states implantation of a kardiovertera-defibrillator is carried out. Everything is recommended to patients correction of a way of life: administration of drugs, an interval (antianginalny, antidiuretichesky, gipolipidemichesky, psychotropic and some other drugs) extending QT is forbidden, it is required to limit physical activities and other triggers of attacks of paralyzes.
Forecast and prevention
Regular medical control of a condition of patients allows to avoid syndrome complications, and correctly picked up treatment, observance of recommendations about the mode of physical activity promote improvement of quality of life of patients. It is impossible to prevent development of hereditary diseases. Children from risk group (with the burdened family anamnesis) need carrying out ECG screening and the molecular and genetic analysis right after the birth. Early diagnosis and regular monitoring of a disease provide higher efficiency of therapy.