Кабуки синдромы: Сирек кездесетін генетикалық ауру

Kabuki syndrome (previously known as Kabuki makeup syndrome (KMS) or Niikawa–Kuroki syndrome) is a rare congenital disorder of genetic origin. It affects multiple parts of the body, with varying symptoms and severity, although the most common is the characteristic facial appearance. Kabuki syndrome affects roughly one in 32,000 births. It was first identified and described in 1981 by two Japanese groups, led by scientists Norio Niikawa and Yoshikazu Kuroki. It is named Kabuki syndrome because of the facial resemblance of affected individuals to stage makeup used in kabuki, a Japanese traditional theatrical form. Infants and young children often experience difficulties relating to hypotonia, feeding issues/failure to thrive, infections, surgical repair of heart and palate defects and developmental delays. Young children with Kabuki syndrome benefit from early intervention services. School age children tend to have fewer medical issues requiring hospitalization, though frequent infections, hearing loss and feeding issues occur. In addition, intellectual impairment, difficulty with visuospatial tasks and maintaining attention usually require an IEP (individualized education plan) if the child attends public school. Older children and adults report difficulties with anxiety. Endocrine abnormalities and immune system abnormalities such as ITP (idiopathic thrombocytopenia) and CVID (common variable immune deficiency) are medical issues that tend to present in older children, adolescents and adults.

Type 1 Kabuki syndrome is caused by germline heterozygous loss of function variants in KMT2D (formerly known as the MLL2), located on human chromosome 12. or loss of function point variants involving KDM6A (formerly known as UTX), located on the X chromosome. Approximately 5% of cases of Kabuki syndrome are of Type 2. Type 2 Kabuki syndrome demonstrates an X linked dominant pattern of inheritance. Most cases of Kabuki syndrome occur de novo, that is, the parents are unaffected and the gene was mutated early in embryological development. However, several cases of inherited mutations causing Type 1 or Type 2 Kabuki syndrome are now known. Under normal circumstances, these enzymes transfer methyl groups on and off histones to regulate genes via epigenetic pathways. When the genes that encode these enzymes are mutated, epigenetic activation of certain developmental genes is impaired and developmental abnormalities occur, leading to the characteristics of Kabuki syndrome patients.

Due to its rarity, Kabuki syndrome is not screened for in routine prenatal testing including blood tests, chorionic villus sampling (CVS), or amniocentesis. Although not routine for the general population, if Kabuki syndrome is a specific concern (i. e. expectant mother who has been diagnosed with Kabuki syndrome or sibling with KS), it is possible to test for one of the specific mutations.

A summary of recommended evaluations can be found here. Newly diagnosed patients with Kabuki syndrome will often undergo tests that are aimed at detecting common abnormalities associated with the syndrome. They include an echocardiogram (ultrasound of the heart) for detection of structural heart defects, kidney ultrasound for detection of structural renal abnormalities, immunoglobulin levels, pneumococcal titers and a hearing screening test. Further evaluation and testing by specialists may be indicated in addition to cardiology, nephrology, allergy/immunology, audiology mentioned above. This may include orthopedics (such as hip dysplasia), pulmonary (sleep study to rule out obstructive sleep apnea due to hypotonia), ophthalmology evaluation (vision screen), ENT evaluation (hearing evaluation), Neurology evaluation (i. e. if seizures present), Hematology evaluation (if bleeding disorder), GI evaluation (if gi abnormalities), or others as needed. There are currently no Kabuki syndrome specific treatments and there is no cure. Treatment plans are customized to address the symptoms the individual is experiencing. The disease appears to affect all population groups equally, with no differences based on sex, race, or environment. In 2023, a project called Kabuki Count was launched by a global collection of patient advocacy groups (led by the Kabuki Syndrome Foundation) as a global census to document how many people have Kabuki syndrome worldwide.

Research on Kabuki syndrome is limited due to its low incidence. In the UK, Prof Siddharth Banka's group at the University of Manchester and Manchester University Hospitals has a research program for Kabuki syndrome. In Canada, Dr. Rosanna Weksberg at SickKids and University of Toronto. Several European groups based in Italy, France, Germany and the Netherlands are also actively working on improving understanding of the condition and to identifying potential treatments. In 2018, the Kabuki Syndrome Foundation was established to accelerate research efforts to treat or cure Kabuki syndrome. They launched the Kabuki Syndrome Outcome measures and Biomarkers Consortium (KSOC) in 2023 which is a collaborative clinical research study of Kabuki syndrome biomarkers.

In 1969, Norio Niikawa MD, a geneticist in Japan was treating a child patient presenting with unique facial characteristics and various health problems. Never having seen this constellation of symptoms before, Dr Niikawa wondered if he was faced with an undiagnosed condition, a disorder with a genetic basis. Over the next several years, this physician treated several other patients with the same symptoms in his outpatient genetics clinic, furthering support for a disorder never before diagnosed. In 1979, Dr Niikawa presented his findings and hypothesis at the first Japan Dysmorphology Conference. A fellow physician at this conference, Yoshikazu Kuroki, recognized the symptoms, and realized that he had also seen several paediatric patients with this presentation; he presented two of his own cases at the second annual conference the following year. In 1981, the two doctors separately submitted articles on this new diagnosis to the Journal of Pediatrics. Dr Niikawa coined the term 'Kabuki syndrome' (also known as Kabuki make up syndrome or Niikawa–Kuroki syndrome) as a reference to traditional Japanese theatre which he respected greatly. Many of the children presenting with this diagnosis had unusual, elongated lower eyelids, and this feature was reminiscent of the theatrical make up worn by actors in Kabuki theatre. As reported by Dr. Niikawa "The name, 'Kabuki make up', of the syndrome was given by myself, because the facial appearance of patients, especially eversion of their lower eyelids, is reminiscent of the makeup of actors in Kabuki, the traditional form of Japanese theater. Kabuki was founded early in the 17th century in Japan and over the next 300 years developed into a sophisticated form of theater. Kabuki actors usually apply traditional makeup to strengthen their eyes, especially in a hero play, and they are very proud of their performing art." The individual kanji, from left to right, mean sing (歌), dance (舞), and skill (伎). Kabuki is therefore sometimes translated as "the art of singing and dancing". The genes for Kabuki syndrome were discovered in 2010 and 2012 for Type 1 and Type 2 Kabuki syndrome respectively.

The Good Doctor is an American medical drama television series that airs on ABC. Season five's ninth episode features Matthew Horner, an actor with Kabuki syndrome. Horner is likely the first actor with Kabuki syndrome to be cast in a major network TV drama. Nineteen Paper Cranes is a short documentary by Michael Joseph McDonald. The film follows a deaf Japanese papermaker with Kabuki syndrome as she memorializes the nineteen victims of the Sagamihara stabbings.