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.
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
Rebecca Foulger (Genomics England curator)
Group: Other
Workplace: Other
List | Entity | Reviews | Mode of inheritance | Details | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Green List (high evidence) |
KDM6A |
4 reviews3 green |
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Green List (high evidence) |
KMT2D |
4 reviews3 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Red List (low evidence) |
PQBP1 |
2 reviews1 red |
X-LINKED: hemizygous mutation in males, biallelic mutations in females |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Red List (low evidence) |
RAP1A |
2 reviews2 red |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Red List (low evidence) |
RAP1B |
2 reviews1 red |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
03.04.2016 Expert reviews assessed, panel revised and promoted to version 1.