Pallister-Killian syndrome is an extremely rare genetic disease that occurs with tetrasomy on the 12th chromosome. Its development is associated with the X-recessive type of inheritance. The condition is manifested by multiple pathologies of the perinatal period, severe forms of mental retardation, various congenital anomalies of internal organs and stigmas of dysembriogenesis. Diagnosis includes genetic testing, instrumental imaging (ultrasound, CT, MRI), neurological examination. Patients are prescribed supportive treatment, a comprehensive rehabilitation program, and regular follow-up.
Q99.8 Other specified chromosomal abnormalities
Pallister syndrome (Pallister-Killian) has synonymous names tetrasomy 12p, mosaic isochromosome syndrome 12p. It is extremely rare, there are data on 30 cases of the disease in the medical literature. Pathology was first described in 1977 by the scientist F. Pallister. In 1981 M. Tesler-Nikola and V. Killian independently characterized the clinical picture of the syndrome in more detail. The first prenatally diagnosed case of the disease dates back to 1985 .
The disease occurs due to a rare mosaic chromosomal disorder, in which 4 copies of the short arm of chromosome 12 are formed in the genetic material of the cell instead of two that should be present normally. These additional copies are usually located in one of the chromosomes (isochromosome). It is assumed that Pallister-Killian syndrome has an X-linked recessive type of inheritance, but there is not enough data to confirm this hypothesis.
The disease appears as a result of gene disorders caused by the presence of the mosaic clone mos 47,+ i(12)(p10)/46. The mutation is formed when the sister chromatids do not disperse in the phase of meiosis II during the formation of female germ cells. After fertilization of such an egg, there is a postzygotic erroneous division of the centromere and its partial loss during subsequent mitoses, therefore only a part of the cells of the child’s body have tetrasomy 12p.
Pallister’s syndrome is a serious disease that can end with intrauterine fetal death. In other cases, the anamnesis determines the pathologies of the course of pregnancy in the form of early toxicosis, the threat of termination at a later date, delays in fetal development. Newborns have neurological complications due to hypoxic-ischemic encephalopathy, problems with independent breathing, an average or low score on the Apgar scale.
Patients with Pallister-Killian syndrome have specific features of the facial skeleton: a protruding forehead with an inflated hairline, low-set deformed ears, a wide distance between the eyes. There are also a small upturned nose, turned-out nostrils, a large distance from the lower edge of the nostrils to the upper lip. Depigmentation foci are detected on the skin of the body.
The characteristic features of the syndrome include the disproportionate development of the limbs with a shortening of their proximal sections, which is accompanied by joint contractures, persistent limitation of the volume of active movements. Problems with hearing and vision are often bothered. Pallister-Killian syndrome is characterized by heart defects (ventricular septal defect, aortic coarctation, open Botall duct), diaphragmatic hernia.
Tetrasomy 12p has a delay in psychomotor development, mental retardation. Children start to roll over late, sit and crawl, often they do not speak even at the age of 1-3 years, but only pronounce individual sounds (gulling) or syllables. There is a lag in growth and physical development, patients gain body weight poorly, have an asthenic physique. Neurological disorders are manifested by epilepsy, muscle hypotension, tremor.
Those suffering from Pallister’s disease have multiple defects against the background of severe neurological deficit, which causes early disability of such patients. Complications of the syndrome are associated with delayed speech and mental development, which is why patients need constant care, qualified medical care. An unfavorable outcome is usually observed in severe congenital malformations that are difficult to correct surgically.
Timely diagnosis is difficult, due to the great rarity of Pallister-Killian syndrome, the presence of tissue-specific mosaicism, which creates difficulties in genetic analysis. Before visiting a geneticist, such children are often examined by a large circle of specialists: pediatricians, neurologists, cardiologists, endocrinologists. The following methods are prescribed for the diagnosis of Pallister-Killian syndrome:
- FISH analysis. This method of genetic testing is the most accurate for determining tetrasomy 12p. Buccal epithelial cells or fibroblast culture are used for the study, among which up to 50-65% have a characteristic mutation. When analyzing lymphocytes, only 2% of cells show an additional short arm of the 12th chromosome.
- Consultation of a neurologist. Patients are recommended a detailed neurological examination with an assessment of reflex excitability, muscle tone, and the level of development of psychomotor functions. Be sure to check the senses, because such children often have hearing loss, decreased vision.
- Instrumental methods. To identify concomitant congenital malformations, a comprehensive examination is performed using ultrasound of the abdominal cavity, chest X-ray, echocardiography. According to the indications, neurosonography, CT or MRI of the brain is performed.
Special treatment methods for Pallister syndrome have not yet been developed. The therapy is based on supportive measures that reduce the clinical manifestations of the disease, stimulate the formation of missing psychomotor skills, and help to adapt the patient to life with disabilities. The treatment plan for the syndrome includes several directions:
- Metabolic drugs. Medications that stimulate energy metabolism, as well as vitamin and mineral complexes and homeopathic remedies are prescribed to support the work of the myocardium, improve the functioning of the nervous system.
- Rehabilitation. Patients are shown a comprehensive rehabilitation program with the participation of physical therapy instructors, specialists in mechanotherapy, defectologists. Such activities are aimed at developing children’s oral speech, communication skills, and improving motor functions.
Heart defects that occur with the syndrome require surgical correction, which is mainly carried out in the first year of a child’s life. The timing of cardiac surgery is determined by the severity of circulatory disorders.
Prognosis and prevention
Taking into account the absence of etiopathogenetic methods of Pallister syndrome therapy, the severity of clinical symptoms and the formation of disability at an early age, the prognosis is unfavorable. Since the purpose of the ongoing therapeutic measures is to improve the quality of life of patients, with their successful implementation, it is possible to significantly develop psychomotor skills. There is no specific prevention of the syndrome.