Kabuki syndrome: symptoms, causes, diagnosis and support

Contact, the charity for families with disabled children, describes Kabuki syndrome as a genetic condition that results in a typical pattern of physical and developmental problems. It is also known as Kabuki make-up syndrome or Niikawa-Kuroki syndrome. Kabuki UK, the specialist charity, says it was first identified in 1981 by two independent groups of Japanese doctors, and that it affects people of all ethnic backgrounds.

NHS England's genomics education programme (GeNotes) calls it a rare genetic condition characterised by typical facial features, short stature, developmental delay or intellectual disability, congenital heart anomalies and cleft palate, among other features.

It is a genetic condition rather than an infection, so it cannot be caught from another person.

Kabuki UK says it presents a wide range of symptoms, which vary from person to person. Contact lists the following.

• A distinctive facial appearance with long eye openings that may slant upwards, arched eyebrows and prominent ears.

• Congenital heart defects in almost half of children.

• Cleft palate or palate dysfunction, and kidney, bowel and dental problems.

• Floppiness (low muscle tone) and loose joints in most infants.

• Feeding difficulties in infancy; many children need tube feeding and some need a gastrostomy, and difficulties tend to resolve with age.

• Susceptibility to infections, especially ear infections; many need surgery for middle ear problems.

• Speech and motor delay with mild-to-moderate learning disability; most children need extra help in school.

• Slow growth with a final height usually below that predicted by parental heights, and in some children growth hormone deficiency.

• A tendency to put on weight, particularly around the trunk, from mid-childhood.

NHS England GeNotes lists a wider range of features that may be present, though not every person has them all. The table groups them by body system.

Contact says about 55 to 80 per cent of patients have a change (mutation) in the KMT2D gene, located on chromosome 12, and around 5 per cent have changes in the KDM6A gene on the X chromosome. In a small proportion, the underlying genetic abnormality is unknown. NHS England GeNotes gives about 75% for KMT2D and 5% for KDM6A.

Kabuki UK explains that KMT2D regulates the expression of other genes during development, and that KDM6A plays a similar role. GeNotes says changes in either gene disrupt the way DNA is packaged and read.

KDM6A-related Kabuki syndrome is X-linked. GeNotes says females with it tend to have milder features than males, who are typically more severely affected.

Contact says that in the majority of children the KMT2D or KDM6A change is a new event with neither parent carrying it, and the recurrence risk for parents in these cases is extremely low. GeNotes puts the chance of recurrence in a future pregnancy at less than 1% when neither parent carries the variant.

An individual with Kabuki syndrome has a 50% chance of passing the gene change to their child in every pregnancy. A child with a KMT2D change would be affected. With a KDM6A change, the effect depends on the child's sex.

Contact says prenatal diagnosis is possible in families where the risk is high and a gene change has been identified. A clinical genetics service can explain testing and family planning options.

Contact says it is usually diagnosed on the basis of clinical and developmental features and confirmed by testing the KMT2D and KDM6A genes.

GeNotes says international consensus diagnostic criteria have been published since 2019. A definite diagnosis can be made at any age with a history of low muscle tone in infancy, developmental delay and/or intellectual disability, plus either a pathogenic or likely pathogenic variant in KMT2D or KDM6A, or typical facial features at some point in life. People with a probable or possible diagnosis should be considered for genomic testing through the NHS Genomic Medicine Service.

Contact says there is no curative treatment, but the majority of the physical problems can be treated symptomatically. Children usually learn at a slower rate, and special educational input can help them reach their potential.

GeNotes says management is complex and should be delivered by a multidisciplinary team, and that individuals are likely to need input from clinical genetics, community paediatrics, ophthalmology, audiology, endocrinology and cardiology. Kabuki UK adds that early intervention with speech, occupational and physical therapy can help developmental delay, and that ongoing monitoring of medical issues is essential.

Short stature may respond to growth hormone therapy, so GeNotes suggests considering referral to endocrinology.

Contact offers a freephone helpline for parents of disabled children, emotional support through a Listening Ear service and parent guides. Kabuki UK is a registered charity providing information and support to families affected by Kabuki syndrome, advice to newly diagnosed families and events that let families meet.

See a GP if you are concerned about a baby's or child's development, feeding, hearing, repeated ear infections or growth. A paediatrician can arrange assessment and referral to genetics. If you or your child has Kabuki syndrome, contact your specialist team if there are new symptoms, such as breathing difficulties, severe infections, fits or a sudden change in health, or use NHS 111 or 999 in an emergency.

On the NHS, a child with suspected Kabuki syndrome is usually referred by a GP or paediatrician to a clinical genetics service, which arranges genomic testing and coordinates specialists. Whichever route is used, the same multidisciplinary follow-up applies. Ask for results to be shared with your GP and health visitor or school nurse so support is joined up.