Kabuki syndrome is a rare phenomenon in clinical practice, but several distinct features distinguish this syndrome from an array of disorders presenting with similar signs and symptoms [1] [2] [3] [4]:

• Facial changes - Virtually all patients suffering from Kabuki syndrome have large, cupped ears, very broad and arched eyebrows, elongated palpebral fissures that are often accompanied by eversion of the lower lid (particularly the lateral third), and a depressed nasal tip [1] [4].
• Intellectual disability - Present in up to 92% of patients, intellectual impairment is an important manifestation of Kabuki syndrome [2] [4]. Many patients often have a delayed development of speech along with difficulties in cognition and understanding of words [2] [4].
• Growth deficiency - Despite having a normal height at birth, postnatal growth retardation is reported in a significant percentage of cases [1] [3] [4].
• Skeletal anomalies - Malformation of the spinal column (scoliosis, vertebral deformities), a cleft hand, brachydactyly, a shortened fifth finger of the hand, and underdeveloped ribs are notable disorders of the skeletal system [1] [2] [4].
• Skin - persistent fetal finger pads and abnormal dermatoglyphic patterns are hallmarks of Kabuki syndrome [1] [2] [3] [4].

In addition to these five crucial types of changes, other manifestations may stem from the cardiovascular system (mainly in the form of congenital heart disease such as coarctation of the aorta, atrial septal defects, and ventricular septal defects), gastrointestinal system (anal atresia), the eye (ptosis, strabismus), and the oral cavity (hypodontia and widely spaced teeth) [1] [2] [3] [4]. Furthermore, hearing loss, predisposition to infections and autoimmune diseases, and feeding issues are also noted [1] [2] [3] [4].

• Short Stature

  These investigators described a group of patients sharing typical facial features, skeletal anomalies, mental retardation, short stature, and dermatoglyphic anomalies. [ncbi.nlm.nih.gov]

  Kabuki syndrome is a rare, congenital disorder characterized by distinctive facial features, growth delays, mild-to-moderate intellectual disability, skeletal abnormalities and short stature. [kennedykrieger.org]

• Developmental Delay

  They may also experience developmental delays and sensory processing disorders. Often, their behavior is similar to patterns associated with autism or obsessive-compulsive disorder. [webmd.com]

  Kabuki syndrome is a rare genetic disorder characterized by congenital anomalies and developmental delay. It is often associated with impaired immune response and autoimmune abnormalities. [ncbi.nlm.nih.gov]

• Feeding Difficulties

  We believe that KS is a newly recognized cause of syndromic CHI and that this diagnostic should be envision in CHI patients presenting with feeding difficulties, mental retardation, malformations and/or facial dysmorphism. [ashg.org]

  Facial dysmorphisms (94%), feeding difficulties (100%) and hypotonia (100%) suggested the clinical diagnosis of KS. No significative differences in terms of facial features were noticed between mutation positive and negative patients of the cohort. [ncbi.nlm.nih.gov]

  Growth, gastrointestinal and feeding issues Feeding difficulties. Poor sucking. Poor swallowing. Malabsorption. Gastroesophageal reflux. Short stature. Some children with Kabuki syndrome may develop behavioral issues. [my.clevelandclinic.org]

  The disorder affects males and females, and can affect different organs and cause a variety of problems that our team is able to treat and address, including: Growth deficiency Feeding difficulties Low muscle tone in early years Seizures Hearing issues [kennedykrieger.org]

• Failure to Thrive

  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. [senteacher.org]

  If the stature is normal at birth, neonates soon present with growth delay and frequent failure to thrive of variable severity. Microcephaly is inconstant. [orpha.net]

• Marcus-Gunn Pupil

  Prevalence figures of microphthalmia vary from 0.0092% to 0.15% in defined areas and in ophthalmic outpatient clinic.[16][17][18][19][20] Ophthalmologic features such as Marcus Gunn pupil (a type of relative afferent pupil defect that causes a pathologically [eyewiki.aao.org]

• Hearing Impairment

  Recurrent otitis media (12/14) and hearing impairment (8/14) were also more common features. [ncbi.nlm.nih.gov]

  Patients can also develop heart defects, urinary tract problems, abnormal dentition, hearing impairments, early puberty, seizures, and recurrent infections. [pdkselayang.blogspot.com]

  impairment Conductive deafness Conductive hearing loss [ more ] 0000405 Failure to thrive Faltering weight Weight faltering [ more ] 0001508 Feeding difficulties Feeding problems Poor feeding [ more ] 0011968 High palate Elevated palate Increased palatal [rarediseases.info.nih.gov]

  Rena Ellen Falk and Arti Pandya, Hereditary Hearing Impairment, Emery and Rimoin's Principles and Practice of Medical Genetics, 10.1016/B978-0-12-383834-6.00150-6, (1-38), (2013). [doi.org]

  Say B, McCutcheon L, Todd C and Hough JV (1993) Kabuki make‐up syndrome and hearing impairment. Clinical Dysmorphology 2: 68–70. [els.net]

• Broad Eyebrows

  Typical dysmorphic features include long palpebral fissures with eversion of the lateral third of the lower eyelid and two or more of the following: (1) arched and broad eyebrows with the lateral third displaying notching or sparseness; (2) short columella [ncbi.nlm.nih.gov]

  (The typical facial features: elongated palpebral fissures with eversion of the lateral third of the lower eyelid; arched and broad eyebrows; short columella with depressed nasal tip; and large, prominent, or cupped ears) Dental. [flipper.diff.org]

  Free Books & Documents Excerpt Clinical characteristics: Kabuki syndrome (KS) is characterized by typical facial features (long palpebral fissures with eversion of the lateral third of the lower eyelid; arched and broad eyebrows; short columella with [pubmed.ncbi.nlm.nih.gov]

  The specified clinical findings include arched and broad eyebrows with notching or sparseness of the lateral third, short columella and depressed nasal tip, large, prominent, or cupped ears, and persistent fingertip pads. [heraldopenaccess.us]

  Patients often have long palpebral fissures with eversion of the lateral one-third of the lower eyelids and arched and broad eyebrows that resemble the make-up of actors in Kabuki, the traditional Japanese play. [genome.jp]

• Brachydactyly

  The proposita had arched eyebrows, long and upward slanting palpebral fissures, cleft lip and palate, retromicrognathia, brachydactyly of hands and feet, stubby fingers, nail hypoplasia, and prominent finger pads. [ncbi.nlm.nih.gov]

  Skeletal anomalies - Malformation of the spinal column (scoliosis, vertebral deformities), a cleft hand, brachydactyly, a shortened fifth finger of the hand, and underdeveloped ribs are notable disorders of the skeletal system. [symptoma.com]

  Musculo-skeletal anomalies include brachydactyly V, brachymesophalangy, clinodactyly of fifth digits, spine abnormalities and joint hypermobility and dislocations. [orpha.net]

• Joint Dislocation

  This strengthens muscle tone and lessens the chance of joint dislocations. Occupational therapy helps develop coordination and fine-motor skills. Speech therapy. [hcpro.com]

  Furthermore, we show that MLL2 mutation-positive KS patients are more likely to have feeding problems, kidney anomalies, early breast bud development, joint dislocations and palatal malformations in comparison with MLL2 mutation-negative patients. [ncbi.nlm.nih.gov]

  In general, those with a KMT2D mutation are also more likely to have renal anomalies, feeding problems, premature thelarche in females, joint dislocations, and palatal anomalies than are those without a KMT2D mutation. [flipper.diff.org]

  The hypermobility type of Ehlers-Danlos syndrome resembles KS in that patients with both conditions can have loose/lax joints, joint dislocations, and blue sclerae. [forgottendiseases.org]

  However, as children enter adolescents, they have a tendency to gain too much weight, which can make other health problems (such as joint dislocations) worse. [rarediseases.org]

• Muscle Hypotonia

  This two-year old boy was referred to our hospital at 3-months of age for his growth retardation and muscle hypotonia. Because of his peculiar face, brachydactyly V and fingertip pad, we diagnosed him as having Kabuki syndrome. [ncbi.nlm.nih.gov]

Because the diagnosis is primarily based on clinical criteria (but also because the disorder could be life-threatening in the absence of early recognition, particularly if congenital heart disease is present), a thorough clinical assessment is vital. The physician must take a detailed patient history during which the onset of symptoms and signs and their progression should be evaluated. Some studies have established the autosomal dominant pattern of inheritance in a significant number of patients meaning that a family history might provide important clues to the diagnosis [1] [2]. The majority of signs can be detected at the physical examination, but certain imaging studies may be necessary. As congenital heart diseases are often present [2], cardiac ultrasonography is a useful study. Once solid evidence is raised through clinical findings, genetic studies should be sought. Many patients develop Kabuki syndrome without a familial component (through de novo mutations) [1] [2]. The analysis of two genes - KMT2D (involved in the autosomal dominant form) and KDM6A (responsible for sporadic forms) will confirm the diagnosis [1] [2] [3] [4] [5] [6].

This ratio decreased in the first year of treatment from −1.81 SDS to −1.45 SDS and remained stable during further treatment. Throughout this study, every participant received rhGH treatment for a duration of 24 months. [karger.com]

Information about a therapy, service, product or treatment does not in any way endorse or support such therapy, service, product or treatment and is not intended to replace advice from your doctor or other registered health professional. [betterhealth.vic.gov.au]

Management and Treatment How is Kabuki syndrome treated? There’s no cure for Kabuki syndrome. Treatment for the condition focuses on alleviating your child’s specific symptoms. It can also help reduce the risk of complications. [my.clevelandclinic.org]

Due to the lack of treatment in the KS, the aim is to develop a model of this disease from fibroblasts from patients and reprogram them into mesenchymal stem cells. [clinicaltrials.gov]

Standard Therapies Treatment There is no specific treatment for Kabuki syndrome. Treatment is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. [rarediseases.org]

Treatment and prognosis Variable, depending on the degree of neuromuscular dysfunction and organ dysplasia. History and etymology "Kabuki" refers to a type of Japanese drama in which the players appear in stylized makeup. [radiopaedia.org]

For patients with lower lip pits, a thorough evaluation should be made to distinguish between VWS and KS, as there are differences in long-term prognosis. [ncbi.nlm.nih.gov]

Prognosis Although morbidity is significant, prognosis is quite favorable. Life expectancy is somewhat dependent on cardiac and immunologic complications. The documents contained in this web site are presented for information purposes only. [orpha.net]

The second objective of the study was to explore possible etiological clues found in our data and from review of the literature. [ncbi.nlm.nih.gov]

Summary Epidemiology KS was initially described in Japan, but has now been observed in all ethnic groups. Prevalence estimation is approximately 1:32,000. Clinical description KS has a wide and variable clinical spectrum. [orpha.net]

Congenital eye malformations: clinical-epidemiological analysis of 1,124,654 consecutive births in Spain. Am J Med Genet 1998;75:497-504. ↑ Kallen B, Robert E, Haiirs J. The descriptive epidemiology of anophthalmia and microphthalmia. [eyewiki.aao.org]

Taken together, our studies suggest that the KS pathophysiology overlaps with the RASopathies and provide a potential direction for treatment design. [ncbi.nlm.nih.gov]

Conclusion: Association of cervical arterial disease with this syndrome has never been described, and its pathophysiology is not yet established; however, it can direct future research and maybe treatment. [surgicalneurologyint.com]

Pathophysiology[edit] The KMT2D and KDM6A genes belong to a family of genes called chromatin-modifying enzymes. [en.wikipedia.org]

Kabuki syndrome (KS) is a multiple congenital anomaly syndrome in which ophthalmological examination for the early detection of ocular abnormalities is desired in order to prevent visual impairment. [ncbi.nlm.nih.gov]

[…] cause and the exact emergence of the disease is not yet clear, preventive measures are also not yet known. [healthzene.com]

Prevention How can I prevent Kabuki syndrome? You can’t prevent Kabuki syndrome because it’s a genetic condition. The genetic mutation that causes this condition most often happens randomly. [my.clevelandclinic.org]

The importance of early diagnosis is to provide preventive management and an appropriate genetic counseling for the family. [dialnet.unirioja.es]

1. Adam MP, Hudgins L, Hannibal M. Kabuki Syndrome. 2011 Sep 1 [Updated 2013 May 16]. In: Pagon RA, Adam MP, Ardinger HH, et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
2. Cheon C-K, Ko JM. Kabuki syndrome: clinical and molecular characteristics. Korean J Pediatr. 2015;58(9):317-324.
3. Hannibal MC, Buckingham KJ, Ng SB, Ming JE, et al. Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome. Am J Med Genet A. 2011;155A:1511–1516.
4. Kasdon BD, Fox JE. Kabuki syndrome: diagnostic and treatment considerations. Ment Health Fam Med. 2012;9(3):171-179.
5. Makrythanasis P, van Bon BW, Steehouwer M, et al. MLL2 mutation detected in 86 patients with Kabuki syndrome; a genotype-phenotype study. Clin Genet. 2013;84:539–545.
6. Ng SB, Bigham AW, Buckingham KJ, et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet. 2010;42:790–793.