* 본 콘텐츠는 가부키 증후군 환자를 진료하는 의료진을 위한 참고 자료입니다.
Kabuki Syndrome is a rare multiple anomaly syndrome with an estimated incidence of around 1 in 32,000.
It was first described in 1981 by Drs Niikawa and Kuroki, working independently in Japan. The name was selected because of the facial resemblance to the makeup used in traditional Japanese Kabuki theatre. The spectrum of medical problems seen in Kabuki syndrome is diverse but all patients have similar facial features with long palapebral fissures, everted lower eyelids and arched eyebrows. A variable degree of learning disability is usually present. The cause of Kabuki remains unknown but is most likely genetic.
Kabuki Syndrome Guideline Development Project
The guidelines have been developed using a robust methodology based on the one utilised by the Scottish Intercollegiate Guidelines Network (SIGN). The method has been adapted to suit rare conditions where the evidence base is limited, and where expert consensus plays a greater role.
Kabuki Syndrome Clinical Management Guidelines
1. What are the aims of the guidelines?
The guidelines aim to provide clear and wherever possible, evidence-based recommendations for the management of patients with Kabuki Syndrome.
2. Who are they aimed at?
As KS is rare, it is unlikely that many of the healthcare professionals usually responsible for managing and co-ordinating the care of people with the condition will have had much prior experience of the syndrome. As KS is a multisystem disorder, people with KS may require various diagnostic and screening tests, assessments, referrals and multidisciplinary interventions at different stages of their lives. These guidelines lay out these requirements in a clear format that is easily accessible to anybody involved in the care of an individual with KS. Though much of the information is relevant to all with KS, we have in the main used information relevant to a European audience.
Though these guidelines have been prepared principally for professionals, they will also be of interest to the parents of Kabuki syndrome children. If you are reading these guidelines as a parent we would emphasise that your child may not be affected by all the complications mentioned herein as every child is an individual. We would recommend that you discuss any terminology or information which may concern you with your child’s doctor.
Diagnosis and First Steps of Management
The cause of KS is unknown, so there is no diagnostic test available. A secure clinical diagnosis is therefore of paramount importance.
The following diagnostic criteria, derived from those suggested by Adam et al. (2005) should be applied:
A clinical diagnosis is extremely difficult to make in neonates.
It may be suggested by the occurrence of prenatal nuchal oedema or the presence of specific malformations which may be associated with KS, but the dysmorphic facial features are often not apparent at this age.
If in doubt it is better to review the infant at a later date before attaching a definite diagnostic label of KS.
1. Characteristic face
- Long palpebral fissures with eversion of the lateral portion of the lower eyelid
- Broad, arched eyebrows with lateral sparseness
- Short columella with depressed nasal tip
- Large, prominent or cupped ears
- Post-natal growth retardation
2. Developmental delay or learning disability
3. Accessory diagnostic criteria
- Fingertip pads
The features of KS change over time and the phenotype is different in adults. Particularly noteworthy are:
- The development of truncal obesity.
- The eyebrows no longer appear interrupted.
- The feet become more striking with overlapping of the toes, the hallux appears long and the fourth and fifth toes appear relatively short.
* At any age, cytogenetic anomalies should be ruled out, using microarray analysis if possible, before a diagnosis of KS can be made.
Differential diagnoses should also be considered.
- Turner syndrome
- Chromosomal imbalances
- Velo Cardio Facial Syndrome (VCFS)
All families should be offered referral to a genetics service at diagnosis, and a key person who will coordinate the management and care of their child should be identified.
Treatment of Manifestations in Individuals with Kabuki Syndrome
Strabismus, refractive error, ptosis, lagophthalmos
- Treatment: Standard treatment per ophthalmologist
- Treatment: Consider pressure equalizing tubes for those w/conductive hearing loss; Hearing aids for those w/sensorineural hearing loss.
- Considerations/Other: Refer to an ENT specialist & audiologist
Cleft lip &/or palate
- Treatment: Standard treatment
- Considerations/Other: Management through a specialized craniofacial clinic is ideal. The palate may be shorter, which can lead to velopharyngeal insufficiency after typical cleft repair.
- Treatment: Orthodontic referral if hypodontia or significant malocclusion is noted
Congenital heart defects &/or arrhythmia
- Treatment: Standard treatment per cardiologist
- Considerations/Other: It is unclear whether risk for aortic aneurysm is ↑; however, if catheterization or angioplasty is being considered, a potential ↑ risk of aortic aneurysm should be communicated to treating team.
- Treatment: Standard treatment, which may incl thickening feeds & appropriate positioning after meals in infants & toddlers. Consider gastrostomy tube.
- Considerations/Other: Pharmacologic treatment for GERD may be considered In those w/severe feeding difficulties &/or poorly coordinated suck & swallow.
- Treatment: Refer to gastroenterologist.
- Considerations/Other: Consider eval for malabsorption &/or celiac disease.
- Treatment: Standard treatment per urologist
Hyperinsulinism & hypothyroidism
- Treatment: Standard treatment per endocrinologist
- Treatment: Consider growth hormone therapy.
- Considerations/Other: Refer to endocrinologist.
- Treatment: Intravenous immunoglobulin therapy may be considered in those w/documented immunoglobulin deficiency.
- Considerations/Other: Refer to immunologist.
- Treatment: Standard anti-seizure treatment per neurologist
- Treatment: No treatment warranted if no other signs of premature puberty
Need for anesthesia
- Treatment: Care in positioning during intubation because of joint laxity, which can affect the cervical spine
- Considerations/Other: Educate regarding potential structural airway anomalies that could make intubation difficult.
Recommended Surveillance for Individuals with Kabuki Syndrome
- Evaluation: Measurement of at least height & weight
- Frequency: At each appointment
- Evaluation: 발달 진행 단계 모니터링
- Frequency: 아동 및 청소년 시기 동안 매 방문마다
- Evaluation: Ophthalmology or optometry to assess vision
- Frequency: At least annually
- Evaluation: Hearing assessment
- Frequency: At least annually
- Evaluation: Clinical evaluation for scoliosis
- Frequency: At each appointment until skeletal maturity
- Evaluation: Thyroid function tests
- Frequency: Every 1~2 years
- Evaluation: Assessment of complete blood count
- Frequency: Every 2~3 years