Comprehensive Guide to Kabuki Syndrome: Diagnosis, Care, and Long-Term Management
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What is Kabuki Syndrome?
Kabuki syndrome (KS) is a rare genetic condition that affects multiple body systems. It was first described in 1981 and is named for the resemblance of the characteristic facial features to the stage makeup used in traditional Japanese Kabuki theater.
KS is caused by changes (variants) in genes that control how the body reads and uses its DNA during development. The two known genes are:
KMT2D — responsible for 55–80% of cases, inherited in an autosomal dominant pattern
KDM6A — responsible for 2–6% of cases, inherited in an X-linked pattern
Approximately 15–20% of individuals with clinical features of KS have no identified gene variant. Most cases occur as new (de novo) variants, meaning neither parent is affected. However, in rare cases, a variant is inherited from an affected parent.
What are the Characteristic Features of Kabuki Syndrome?
KS has five cardinal features
Distinctive facial features
Skeletal anomalies
Persistent fetal fingertip pads (fleshy pads on the tips of the fingers)
Intellectual disability (usually mild to moderate)
Postnatal growth deficiency (short stature that develops after birth)
Distinctive facial features of KS include:
Long openings of the eyelids (long palpebral fissures) with the lower eyelids turned outward at the outer edges
Arched and broad eyebrows, sometimes with thinning or notching of the outer third
A short bridge between the nose and upper lip (short columella) with a flat or depressed nasal tip
Large, prominent, or cupped ears
These facial features may become more recognizable with age and can be subtle in infancy.
What Other Medical Conditions are Associated with Kabuki Syndrome?
Because KS affects many body systems, individuals may experience a wide range of associated conditions. Not every person with KS will have all of these, and severity varies widely.
Heart
Congenital heart defects are found in approximately 28–75% of individuals
Left-sided obstructive lesions (such as aortic coarctation and bicuspid aortic valve) and septal defects are most common
Annual monitoring for aortic dilatation is recommended
Immune system
Increased susceptibility to infections (especially ear infections and sinus infections) affects approximately 44% of individuals
Low immunoglobulin levels (hypogammaglobulinemia) are found in approximately 58%
Autoimmune conditions (such as immune thrombocytopenic purpura, hemolytic anemia, and vitiligo) occur in approximately 14%
KS is now recognized as an inborn error of immunity
Endocrine (hormonal)
Hyperinsulinism (excess insulin production causing low blood sugar) can occur, especially in the newborn period, and may cause serious neurologic harm if untreated
Short stature is common and may respond to growth hormone therapy
Premature breast development (premature thelarche) in girls is the most common endocrine finding (16–41%)
Hypothyroidism and growth hormone deficiency have also been reported
Kidneys and urinary tract
Congenital anomalies of the kidneys and urinary tract are found in up to 62% of individuals in some studies
These may include hydronephrosis, horseshoe kidney, kidney asymmetry, double collecting systems, or kidney agenesis
Cryptorchidism (undescended testes) and hypospadias may occur in males
Gastrointestinal
Feeding difficulties are very common, especially in infancy
Gastroesophageal reflux (GERD) is frequent
Anal atresia and other gastrointestinal malformations may occur
Chronic diarrhea should prompt evaluation for malabsorption or celiac disease
Skeletal
Scoliosis (curvature of the spine)
Short fifth (pinky) fingers
Joint laxity (loose joints)
Hip and knee joint problems
Neurologic
Seizures occur in some individuals
Brain MRI abnormalities have been reported
Microcephaly (small head size) may occur
Eyes and ears
Ptosis (drooping eyelids) and strabismus (crossed eyes)
Hearing loss (both conductive and sensorineural) is common
Frequent ear infections (otitis media)
Mouth and teeth
Cleft lip and/or cleft palate
High-arched palate
Widely spaced teeth, missing teeth (hypodontia), and other dental anomalies
Development and behavior
Developmental delay and intellectual disability (usually mild to moderate, but variable)
Some individuals show features of autism spectrum disorder
Many individuals with KS are described as sociable and friendly
Growth and weight
Failure to thrive is common in infancy
A tendency toward overweight or obesity may develop in early childhood
How is Kabuki Syndrome Diagnosed?
Diagnosis is based on the 2019 International Consensus Diagnostic Criteria.
A definitive diagnosis requires a history of infantile hypotonia (low muscle tone) and developmental delay and/or intellectual disability, PLUS one or both of the following:
A pathogenic or likely pathogenic variant identified in the KMT2D or KDM6A gene through genetic testing
Typical facial features of KS: long palpebral fissures with eversion of the lateral lower eyelid, PLUS two or more of the following: arched/broad eyebrows with lateral notching or sparseness; short columella with depressed nasal tip; large, prominent, or cupped ears; persistent fingertip pads
Probable and possible diagnoses can also be made when some but not all criteria are met.
Genetic testing (gene sequencing and deletion/duplication analysis of KMT2D and KDM6A) is recommended for all individuals with suspected KS. However, approximately 15–20% of clinically diagnosed individuals will not have an identifiable variant in either gene.
A clinical geneticist is best positioned to evaluate for KS, apply the diagnostic criteria, and coordinate genetic testing and counseling.
What Evaluations are Recommended After Diagnosis?
Once KS is diagnosed, the following evaluations are recommended if not already completed:
Echocardiography (heart ultrasound) with attention to left-sided obstructive lesions and aortic root
Renal ultrasound to screen for kidney and urinary tract anomalies
Hearing evaluation (audiology)
Vision evaluation (ophthalmology)
Immunology evaluation including immunoglobulin levels and lymphocyte subsets
Endocrine evaluation including screening for hyperinsulinism (especially in neonates and young children — a diagnostic fast may be considered), thyroid function, and growth assessment
Developmental assessment
Dental evaluation
Skeletal evaluation if scoliosis or joint problems are suspected
How is Kabuki Syndrome Managed?
There is no cure for KS, but management focuses on treating specific medical issues, supporting development, and preventing complications. Care is individualized and typically involves multiple specialists.
Heart
Standard treatment of congenital heart defects per cardiologist
Annual monitoring for aortic dilatation
Prophylactic antibiotics before dental or surgical procedures may be indicated for those with specific heart defects
If catheterization or angioplasty is being considered, the care team should be informed of a potential increased risk of aortic aneurysm
Immune system
Referral to immunologist for recurrent infections
Intravenous immunoglobulin (IVIG) therapy may be considered for documented immunoglobulin deficiency
Monitoring for autoimmune conditions
Endocrine
Standard treatment for hyperinsulinism per endocrinologist; many individuals with persistent hyperinsulinism respond to diazoxide therapy
Growth hormone therapy may be considered for short stature, with referral to endocrinologist
Premature thelarche alone does not require treatment if there are no other signs of premature puberty
Feeding and gastrointestinal
Thickened feedings and positioning after meals for reflux
Gastrostomy tube placement if feeding difficulties are severe or swallowing is poorly coordinated
Evaluation for malabsorption or celiac disease if chronic diarrhea is present
Hearing and vision
Pressure-equalizing tubes for conductive hearing loss; hearing aids for sensorineural hearing loss; cochlear implants may be considered
Standard treatment for strabismus, ptosis, and refractive errors
Mouth and teeth
Craniofacial clinic management for cleft lip/palate (the palate may be shorter, which can lead to velopharyngeal insufficiency after typical cleft repair)
Orthodontic referral for hypodontia or significant malocclusion
Development and education
Psychoeducational testing and special education services tailored to the child's needs
Evaluation by a developmental pediatrician or psychiatrist if behavior suggests autism spectrum disorder
Speech therapy, occupational therapy, and physical therapy as needed
Seizures
Standard anti-seizure treatment per neurologist
Kidneys and urinary tract
Standard treatment per urologist for hypospadias or cryptorchidism
Nephrology follow-up if structural kidney anomalies are identified
Important Precautions
Anesthesia and surgery
Joint laxity can affect the cervical spine — care must be taken in positioning during intubation
Structural airway anomalies may make intubation difficult — inform the anesthesia team about the KS diagnosis before any procedure
Bleeding risk may be increased in individuals with immune thrombocytopenia — check platelet counts before surgery
Vaccinations
Individuals with documented immune deficiency should be evaluated by an immunologist before receiving live vaccines
Recommended Ongoing Surveillance
Height, weight, and head circumference at each well-child visit (at minimum, yearly)
Developmental milestones at each well-child visit
Vision and hearing monitoring on a yearly basis
Immunoglobulin levels and complete blood count periodically, especially if recurrent infections or signs of autoimmune disease
Endocrine monitoring (growth, thyroid function, blood sugar) as clinically indicated
Cardiac follow-up per cardiologist recommendations
Dental evaluations regularly
Skeletal monitoring for scoliosis
Genetic Counseling and Family Planning
KMT2D-related KS is autosomal dominant: most cases are de novo (new), but if a parent is affected, each child has a 50% chance of inheriting the variant
KDM6A-related KS is X-linked: if the mother carries the variant, each pregnancy has a 50% chance of transmission; affected males typically have more severe features, while carrier females may have variable features
Once a causative variant is identified, prenatal testing and preimplantation genetic testing are available for future pregnancies
Genetic counseling is recommended for all families
Resources
Kabuki Syndrome
GeneReviews: Kabuki Syndrome — Expert-authored clinical summary including diagnosis, management, and surveillance recommendations
MedlinePlus: Kabuki Syndrome — National Library of Medicine resource with patient-friendly overviews of genetics, features, and inheritance
NORD (National Organization for Rare Disorders): Kabuki Syndrome — Disease-specific information, patient assistance programs, and connections to clinical experts
Genetic and Rare Diseases Information Center (GARD) — NIH-supported resource with detailed information and links to clinical trials
All Things Kabuki — Family-run support and information network for families affected by Kabuki syndrome
Genetic Testing and Counseling
National Society of Genetic Counselors — Directory to locate a board-certified genetic counselor
ClinicalTrials.gov — Search for active clinical trials related to Kabuki syndrome
Immune Deficiency
Immune Deficiency Foundation — Education and support for patients with primary immunodeficiency, including resources relevant to KS-associated immune dysfunction
General Support
Global Genes — Rare disease patient advocacy organization providing resources, community connections, and support programs
Questions? Talk with Dr. Duis
Dr. Duis provides comprehensive, whole-person care for complex and rare conditions through our concierge practice. Explore concierge care or contact us.
This guide is for general education and is not medical advice. Talk with your own healthcare provider about your situation. If you are experiencing a medical emergency, call 911.
