Description
Kabuki inclusion criteria (29370)
- At least 3 of the typical dysmorphic features:
  - Arched eyebrows
  - Sparse lateral one third of the eyebrows
  - Long palpebral fissures
  - Everted lower eyelids
  - Ptosis
  - Blue sclera
  - Strabismus
  - Large dysplastic ears
  - Flat nasal tip
  - Broad nasal root
  - Oligodontia
  - Abnormal dentition
  - Full lower lip
  - Pillowed lower lip
  - Lip nodules
  - Lip pits
  - Micrognathia

- AND at least 1 of the following:
  - Developmental delay or Intellectual disability
  - Any of the following malformations
    - Cleft palate
    - Congenital Heart Defect
    - Renal malformation
    - Ocular malformation
    - Gastrointestinal malformation

  - Feeding difficulties or Growth retardation
  - Any of the following neurological problems
    - Microcephaly
    - Seizures
  - Any of the following endocrine/metabolic abnormalities
    - Early onset prominent breasts/areola
    - Hypoglycaemia
    - Growth hormone deficiency
    - Diabetes insipidus
    - Unconjugated hyperbillirubinemia

  - Any of the following limb and skeletal anomalies

    - Persistent fetal pads
    - Brachydactyly or clinodactyly
    - Joint dislocation
    - Joint hypermobility

  - Any of the following immunological abnormalities

    - Frequent infections
    - Low Immunoglobulins
    - Autoimmunity

Kabuki exclusion criteria (29370)
- Those with systemic infections (unlike patients with classical hyper IgE syndrome)

Prior genetic testing guidance (29370)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Kabuki prior genetic testing genes (29370)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 - KMT2D (MLL2)

Closing statement (29370)
These requirements will be kept under continual review during the main programme and may be subject to change.

5 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • Richard Scott (North Thames GMC/UCL)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Siddharth Banka banka (Univesrsity of Manchester)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Helen Savage (Congenica Ltd)

    Group: Other biotech or pharmaceutical
    Workplace: Other clinical service

  • Cristina Dias (The Francis Crick Institute)

    Group: NHS Genomic Medicine Centre
    Workplace: Other

5 Entities

5 reviewed, 2 green

List Entity Reviews Mode of inheritance Details
5 Entitiess
Green Green List (high evidence)
KDM6A
4 reviews
3 green
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Kabuki syndrome 2
  • Kabuki Syndrome Type 2
Tags
Green Green List (high evidence)
KMT2D
4 reviews
3 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
Phenotypes
  • Kabuki Syndrome
  • Kabuki Syndrome Type 1
Tags
Red Red List (low evidence)
RAP1A
2 reviews
2 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review
  • Expert Review Red
Phenotypes
  • Kabuki-like syndrome
Tags
Red Red List (low evidence)
RAP1B
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Red
Phenotypes
  • Kabuki-like syndrome
Tags
No list No list
PQBP1
1 review
1 red
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Literature
Phenotypes
  • intellectual disability
  • long triangular face
  • bulbous nose
  • hypoplastic malar region
  • micrognathia
  • partial agenesis of corpus callosum
  • spasticity
  • contractures
Tags

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