Kabuki Syndrome: Symptoms, Causes, Treatment

He Kabuki syndrome (SK), also known as Kabuki make-up syndrome, is a multisystemic pathology of genetic origin (Pascual-Castroviejo et al., 2005).

At the clinical level, Kabuki syndrome is characterized by the presence of atypical facial features, abnormalities or musculoskeletal malformations, short stature and intellectual disability (Suarez Guerrero and Contreras García, 2011).

This medical condition, first described in 1981 by two Japanese authors, is referred to as Kabuki syndrome due to Similarity between the facial features of the affected individuals and the makeup of the classical Japanese theater actors (Kabuki) (Suarez Guerrero et al., 2012).

Kabuki syndrome is a pathology of genetic origin, being the most cases of sporadic type. Recent studies have pinpointed the possible etiologic cause in a MLL2 mutation (National Organization for Rare Disorders, 2010).

As for the diagnosis, it is fundamentally clinical and is based on observation and analysis of facial features (Alfonso Barrera et al., 2014).

On the other hand, there is no specific treatment for Kabuki syndrome. Because it is a pathology that affects Diverse systems and also has a very variable clinical presentation, therapeutic interventions should be individual and oriented to the treatment of symptoms, medical complications and functional consequences (Alfonso Barrera et al., 2014).

Characteristics of Kabuki syndrome

Kabuki syndrome is a rare multisystemic disorder, characterized by the presence of various anomalies among which Include atypical facial features, generalized retardation of growth, intellectual disability, skeletal malformations, etc. Organization for Rare Disorders, 2010).

This pathology was initially described by Niikawa et al. And Kuroki et al. In 1981 (González Armegod et al., 1997).

Specifically, it was Niikawa who, after describing 62 clinical cases, established the denomination of this pathology as Kabuki makeup (Pascual-Castroviejo et al., 2005).

Kabuki Is the name that receives the classic Japanese theater, in which the actors use a particular facial makeup. Level Visual, this consists of a white base with black eyebrows outlined and arched (Suárez Guerrero and Contreras García, 2011).

Due to the similarity of the facial features characteristic of this syndrome with the artistic makeup of classical theater, for many years it has been Used the term"makeup"in its name. However, at present this is in disuse, being considered a derogatory term (Suárez Guerrero and Contreras García, 2011).

Thus, in the medical literature the most used terms are: Kabuki syndrome or Niikawa-Kuroki syndrome (National Organization for Rare Disorders, 2010).

About us

Although Kabuki syndrome was first described in the Japanese child population, it is a medical condition that can affect all population groups (Orphanet, 2012).

Different epidemiological studies estimate that the prevalence of this pathology could be around 1 case per 32,000-60,000 individuals of the general population (National Organization for Rare Disorders, 2010).

Globally, more than 400 different cases have been described in medical reports (Suarez Guerrero et al., 2012).

Although it is thought that Kabuki syndrome has a similar incidence worldwide, in Spain, until 1997, only 5 cases have been described (González Armegod et al., 1997).

On the other hand, in the case of Latin America, although there are no concrete data, the published cases are Exponential form (González Armegod et al., 1997).

Characteristic signs and symptoms

At the clinical level, 5 defining features of Kabuki syndrome have been defined (Pascual-Castroviejo et al., 2005):

1. Atypical facial features.
2. Skeletal malformations.
3. Abnormalities of dematoglyphs
   (Skin impressions that form the fingerprints and palms of the feet and hands).
4. Intellectual disability.
5. Short stature and generalized growth retardation.

Thus, on the basis of these alterations, some authors categorize these anomalies as major and minor, to facilitate their clinical identification (Alfonso Barrera et al., 2014):

Older posts

• Eyelid fissures (cleft or opening between the eyelids) appear abnormally long, acquiring a Oriental appearance.
• Ectropion or eversion of the lower eyelid: the edge of the lower eyelid turns or rotates and the inner surface is exposed to Exterior.
• Low or Depressed Nasal Bridge: Bone formation of the upper nose may be flatter or lower than normal.
• Arched eyebrows: the eyebrows tend to appear thick, thinning and arching in the more lateral portions.
• Pads on the upper or toe of the fingers.
• Headquarters prominent or malformed.
• Shortening of the 5th finger.
• Palate high or cleft.
• Denture abnormal.
• Hypotonia: low or poor muscle tone.
• Cognitive alterations.
• Low size.
• Hearing loss: Abnormal reduction of hearing ability.

Minor features

• Blue sclera: transparency of choroidal blood vessels through the sclera (white membrane of the eye). At the visual level, You may notice a bluish coloration in the white areas of the eyes.
• Scoliosis: bending or bending of the spine.
• Cardiovascular anomalies.
• Renal malformations.
• Deformed vertebrae.
• Deficiency of different growth hormones.

Causes

Although the specific etiologic causes of Kabuki syndrome have been unknown for a long time, in August 2010, a group of Research from the University of Washington in the USA. UU, published a clinical report in which they indicated the possible genetic causes of this pathology (National Organization for Rare Disorders, 2010).

Kabuki syndrome is a pathology caused by the existence of a mutation in the MLL2 gene, also known as the KTM2D gene. In addition, other cases have also been identified that are associated with a mutation of the KDM6A gene (Genetics Home Reference, 2016).

Specifically, between 55-80% of cases of Kabuki syndrome are due to a mutation in the KMT2D gene. While about 5% of cases are due to a mutation in the KDM6A gene (Genetics Home Reference, 2016).

The KMT2D gene has the fundamental objective of providing instructions for the organism to produce the above 2D methyltransferase present in numerous organs and body tissues. On the other hand, KDM6A gene, in this case, ensures that the Organism produces 6th desmethylase (Genetics Home Reference, 2016).

Both enzymes, Methyltrasnferase And demethylase, regulate the activity of various genes, various research suggests that they work Jointly to control different development processes (Genetics Home Reference, 2016).

Most cases of Kabuki syndrome occur sporadically, that is, in individuals who do not have a family history of this syndrome Medical condition (National Organization for Rare Disorders, 2010).

Apart from this, cases with a family origin have also been identified. Specifically, the mutation of the MLL2 gene can be transmitted to the Offspring, with a 50% risk (National Organization for Rare Disorders, 2010).

Diagnosis

As Boston Children's Hospital (2016) notes, there is no specific test to diagnose Kabuki syndrome.

Usually, this condition is not usually diagnosed in newborn babies (Boston Children's Hospital, 2016). Good part of cases Published have been diagnosed during late childhood or the pre-adolescence stage (González Rmengod, 1997).

Despite this, there are several significant clinical features, such as facial features, stunting, etc., Which allow early detection of a diagnostic suspicion (González Rmengod, 1997).

Therefore, in addition to the individual and family medical history, physical and neurological examination, the Tests to confirm the possible presence of a genetic mutation compatible with
Kabuki (Boston Children's Hospital, 2016).

Treatment

The therapeutic intervention in kabuki syndrome is based mainly on the control of possible medical complications.

During the earliest stages of childhood, it is essential to conduct periodic evaluations that analyze the presence / absence of malformations in Internal organs that may endanger survival (Suarez Guerrero et al., 2012).

In addition, due to the multisystemic involvement, it will often be necessary to design intervention and rehabilitation programs in different Areas: neurological, speech-language, pulmonary, osteomuscular, endocrinological, etc. (Suarez Guerrero et al., 2012).

The fundamental objective of the medical interventions is to improve the clinical prognosis of the person affected and fundamentally, Improve their quality of Life (Suarez Guerrero et al., 2012).

References

1. Alfonso Barrera, E., Martínez Moreno, M., Gozélez Nuño, M., & Díaz Morera, I. (2014). Kabuki syndrome: a disease with heterogeneous prognosis. Rehabilitation (Madr) , 129-132.
2. Boston Children's Hospital. (2016). Kabuki-syndrome . Retrieved from Boston Children's Hospital.
3. González Armengod, C., García-Alix, A., del Campo, M., Garrido, J., & Quero, J. (1997). Kabuki syndrome, a recognizable picture from childhood early. An Esp Pediatr , 429-431.
4. Johns Hopkins University. (2016). KABUKI SYNDROME . Retrieved from Online Mendelian Inheritance in Man.
5. NIH. (2016). Kabuki syndrome . Retrieved from the Genetics Home Reference.
6. NORD. (2010). Kabuki Syndrome . Retrieved from the National Organization for Rare Disorders.
7. Pascual-Castroviejo, I., Pascual-Pascual, S., Velázquez-Fragua, R., & Palencia, R. (2005). Kabuki makeup syndrome. About 18 cases Spanish people. Rev Neurol , 473-478.
8. Suarez Guerrero, J., Ordónez Suarez, A., & Contreras García, G. (2012). Kabuki syndrome. An Pediatr , 51-56.
9. Suarez Guerrero, J., Ordónez Suarez, A., & Contreras García, G. (2012). Kabuki syndrome. An Pediatr (Barc) , 51-56.
10. Suarez-Guerrero, J., & Contreras-García, G. (2012). Kabuki syndrome: clinical characterization, genetic studies, preventive management of Complications and genetic counseling. MED. UIS. , 19-27.