Kabuki Syndrome is a rare genetic disease that occurs once in 32,000 newborns. The appearance of a sick child (phenotype) resembles the make-up of an actor from the ancient Japanese Kabuki theater.
Before the performance, the male actors had a long make-up. The outer corners of the eyes were pulled up and to the side. Some sources use the term "Kabuki makeup syndrome". Sometimes there is an eponymous name - Niikawa-Kuroki syndrome. I especially wanted to highlight the eyes. Many actors sacrificed their he alth and painted eyeballs. The eyebrows were also highlighted, making them curved in an arc. When the performance ended, the character would freeze in place, fix his eyes on one point and squint his eyes.
The disease is manifested by characteristic features of the face in conjunction with mental retardation. Studying families with Kabuki syndrome, revealed an autosomal dominant pattern of inheritance.
Historical background
Described in 1981 by Japanese doctors Niikawa and Kuroki. First studyshowed that out of 60 children, 58 were Japanese. For more than a decade in the medical world, the syndrome was considered a Japanese disease. In 1992, it became apparent that people of any race are susceptible to the disease. Cases of the syndrome have been identified in North America, Arab countries, Belarus. To date, more than 350 cases of pathology have been studied.
Causes of the syndrome
Etiology is not fully understood. A lot of research has been done. We studied the ratio of gender to the disease (50/50), excluded the connection with closely related marriages, did not reveal any pathological effects on the fetus during pregnancy. Karyotyping of all sick children and their parents was carried out. They found gene mutations and tried to bring them under the syndrome, but the studies were refuted.
In 2011, 110 families with Kabuki syndrome were screened, and in 81 cases a mutation in the MLL2 gene was found, but this is not an absolute indicator of the disease. The diagnosis is still made on the basis of the clinical picture. Research is still ongoing.
Clinical signs of disease
Based on a large number of patients examined, the scientist Niikawa and co-authors identified 5 cardinal symptoms of Kabuki syndrome.
- Characteristic face - long palpebral fissures, thick eyelashes, eversion of the lower eyelid (ectropion), wide bridge of the nose, flattened tip of the nose, large protruding ears, eyebrows in the form of arches with a rare growth in their lateral part, low hair growth.
- Skeletal anomalies - skull pathology and microcephaly, gothic palate (high), cleft palate combined with cleft lip, dental anomalies (wide dental gaps, insufficient teeth, malocclusion), growth retardation, short fingers (especially the 5th), sacrococcygeal sinus (epithelial-coccygeal passage), increased joint mobility, scoliosis.
- Change in dermatoglyphics - fetal pads on fingertips.
- Intellectual deficiency of varying degrees. IQ test averages 60-80 points. Children with Kabuki syndrome are more likely to develop autism. Characterized by a violation of behavior, poverty of emotions, a tendency to chew inedible objects.
- Post-natal stunting.
Other symptoms
They accompany the main symptoms of the disease. Any system of the body can be affected.
- Pathology of the cardiovascular system. Any congenital heart disease (tetralogy of Fallot, ventricular or atrial septal defect, coarctation or aortic aneurysm, patent ductus arteriosus) may form.
- Surgical pathology - hernias (umbilical, inguinal, diaphragmatic), anus atresia.
- Disturbances in the digestive system in the form of malabsorption of nutrients (malabsorption), biliary dyskinesia.
- Pathology of the urinary system - dysplasia, horseshoe kidney, splitting of the renal pelvis, duplication and obstruction of the ureters.
- malformations of the external genital organs - cryptorchidism, micropenis.
- Immunodeficiency. Children often develop upper respiratory tract infections and pneumonia. There is an exacerbation of otitis media.
- Endocrine pathology. In infancy, there may be hypoglycemia. Sometimes diabetes mellitus, congenital hypothyroidism, and obesity develop. The level of somatotropic hormone may be reduced. Girls may have precocious puberty.
- Hematological disorders - idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, polycythemia, neonatal hyperbilirubinemia.
- Disorders of the senses. Visual impairment (myopia, astigmatism, incomplete atrophy of the optic nerve. Decreased or loss of hearing (65% of cases).
- Neurological pathology. From birth, there may be a decrease in sucking and swallowing reflexes. Absence nerve palsy, nystagmus, strabismus, drooping eyelids. A third of children have muscle hypotension, which can persist for a long time. As children grow older, they lag behind in psychological and physical development, there is a violation of coordination of movements, a delay in speech development. There may be a tremor of the hands and feet. The development of epilepsy occurs in any age category, girls are more susceptible.
Diagnosis of Kabuki Syndrome
Diagnosis is based on the clinical picture and confirmed by chromosomal studies. A molecular study is underway for a mutation in the MLL2 gene. Some genetic diseases have similar features, it is necessary to conduct a differentialdiagnostics.
It is important to identify serious disorders of organs and systems using a wide range of laboratory and instrumental studies.
Kabuki Syndrome Treatment
There is no specific therapy. Correction of existing disorders in the body. Surgical treatment of heart defects is carried out. Carry out plastic hard palate. In case of hearing impairment, treatment by an otolaryngologist and audiologist is necessary, the issue of a hearing aid is being resolved. Other violations are compensated. Children with Kabuki syndrome need to adapt to the social environment. Families need psychological and material support to raise such a child.
In the January issue of the leading American journal PNAS, an article was published on the treatment of mental retardation in Kabuki syndrome. The essence of therapy is the use of a low-carb ketone diet. Such nutrition helps to achieve an increase in the level of neurogenesis. The study was conducted on laboratory mice at Johns Hopkins University. It has been proven to increase the level of repair of nervous tissue in the brain of animals.
Our compatriot, Doctor of Biological Sciences Varvara Dyakonova commented on the discovery of American colleagues. She believes that nutritional correction is much safer than chemical drugs. There are indications that this method of treatment will help in the treatment of other genetic anomalies associated with mental retardation.
It is known that ketone bodies are metabolites of fat breakdown. Their formation occurs with a lack in the dietcarbohydrates and the transition to protein nutrition. Ketones provide nutrition to the brain, but at the same time, their excess has a toxic effect on the central nervous system. Therefore, the introduction of such a diet into the diet of sick children requires additional testing. Research underway.
Disease Awareness Day - October 23rd
Celebrated in many countries around the world. A special Interregional Association of Disabled Children and Their Parents "Kabuki Syndrome" has been created. The work of a public organization is to support families who are faced with this pathology. In social networks, there are blogs of parents who share their experience in raising and adapting a sick child. People talk about the problem, how to live with it.
Disease and prognosis
Kabuki syndrome has a good prognosis. Life expectancy is affected by the presence of pathology from the cardiovascular system and the degree of immune protection.
