KABUK2
MCID: KBK003
MIFTS: 32

Kabuki Syndrome 2 (KABUK2)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Kabuki Syndrome 2

MalaCards integrated aliases for Kabuki Syndrome 2:

Name: Kabuki Syndrome 2 57 72 29 13 6 70
Kabuk2 57 72
Syndrome, Kabuki, Type 2 39

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
x-linked dominant

Miscellaneous:
severity of phenotype may vary with x-inactivation patterns and/or mutation type


HPO:

31
kabuki syndrome 2:
Inheritance x-linked dominant inheritance


Classifications:



Summaries for Kabuki Syndrome 2

OMIM® : 57 Kabuki syndrome is a congenital mental retardation syndrome with additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids (reminiscent of the make-up of actors of Kabuki, a Japanese traditional theatrical form), a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy (Niikawa et al., 1981). For a discussion of genetic heterogeneity of Kabuki syndrome, see KABUK1 (147920). (300867) (Updated 20-May-2021)

MalaCards based summary : Kabuki Syndrome 2, also known as kabuk2, is related to kabuki syndrome 1 and alacrima, achalasia, and mental retardation syndrome, and has symptoms including seizures An important gene associated with Kabuki Syndrome 2 is KDM6A (Lysine Demethylase 6A). Affiliated tissues include eye and heart, and related phenotypes are atrial septal defect and coarctation of aorta

UniProtKB/Swiss-Prot : 72 Kabuki syndrome 2: A congenital mental retardation syndrome with additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids, a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy.

Related Diseases for Kabuki Syndrome 2

Diseases in the Kabuki Syndrome 1 family:

Kabuki Syndrome 2

Diseases related to Kabuki Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 kabuki syndrome 1 10.1
2 alacrima, achalasia, and mental retardation syndrome 9.9
3 hyperinsulinism 9.9
4 hypoglycemia 9.9

Symptoms & Phenotypes for Kabuki Syndrome 2

Human phenotypes related to Kabuki Syndrome 2:

31 (show all 48)
# Description HPO Frequency HPO Source Accession
1 atrial septal defect 31 occasional (7.5%) HP:0001631
2 coarctation of aorta 31 occasional (7.5%) HP:0001680
3 brachydactyly 31 occasional (7.5%) HP:0001156
4 pulmonic stenosis 31 occasional (7.5%) HP:0001642
5 atrioventricular canal defect 31 occasional (7.5%) HP:0006695
6 cupped ear 31 occasional (7.5%) HP:0000378
7 natal tooth 31 occasional (7.5%) HP:0000695
8 intellectual disability 31 very rare (1%) HP:0001249
9 high palate 31 very rare (1%) HP:0000218
10 hearing impairment 31 very rare (1%) HP:0000365
11 global developmental delay 31 very rare (1%) HP:0001263
12 macrotia 31 very rare (1%) HP:0000400
13 microcephaly 31 very rare (1%) HP:0000252
14 short stature 31 very rare (1%) HP:0004322
15 cleft palate 31 very rare (1%) HP:0000175
16 intrauterine growth retardation 31 very rare (1%) HP:0001511
17 postnatal growth retardation 31 very rare (1%) HP:0008897
18 micrognathia 31 very rare (1%) HP:0000347
19 low-set ears 31 very rare (1%) HP:0000369
20 recurrent otitis media 31 very rare (1%) HP:0000403
21 epicanthus 31 very rare (1%) HP:0000286
22 joint laxity 31 very rare (1%) HP:0001388
23 highly arched eyebrow 31 very rare (1%) HP:0002553
24 protruding ear 31 very rare (1%) HP:0000411
25 hip dislocation 31 very rare (1%) HP:0002827
26 hypodontia 31 very rare (1%) HP:0000668
27 blue sclerae 31 very rare (1%) HP:0000592
28 neonatal hypoglycemia 31 very rare (1%) HP:0001998
29 depressed nasal tip 31 very rare (1%) HP:0000437
30 short columella 31 very rare (1%) HP:0002000
31 hirsutism 31 very rare (1%) HP:0001007
32 generalized hypotonia 31 very rare (1%) HP:0001290
33 lower lip pit 31 very rare (1%) HP:0000196
34 short 5th finger 31 very rare (1%) HP:0009237
35 long palpebral fissure 31 very rare (1%) HP:0000637
36 eversion of lateral third of lower eyelids 31 very rare (1%) HP:0007655
37 prominent fingertip pads 31 very rare (1%) HP:0001212
38 seizure 31 very rare (1%) HP:0001250
39 areolar fullness 31 very rare (1%) HP:0032315
40 behavioral abnormality 31 HP:0000708
41 dental malocclusion 31 HP:0000689
42 feeding difficulties in infancy 31 HP:0008872
43 strabismus 31 HP:0000486
44 decreased body weight 31 HP:0004325
45 sparse lateral eyebrow 31 HP:0005338
46 long eyelashes 31 HP:0000527
47 broad nasal tip 31 HP:0000455
48 hypotonia 31 HP:0001252

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
seizures
hypotonia
developmental delay, mild to severe

Abdomen Gastrointestinal:
feeding difficulties in infancy

Metabolic Features:
neonatal hypoglycemia

Skin Nails Hair Hair:
hirsutism
long eyelashes sparse lateral eyebrows

Head And Neck Ears:
prominent ears
cupped ears (in some patients)
large auricle

Skeletal:
joint hyperlaxity

Growth Height:
less than third centile

Head And Neck Head:
occipitofrontal circumference less than third centile

Chest Breasts:
areolar fullness in infancy

Head And Neck Teeth:
dental malocclusion
hypodontia
abnormal dentition
neonatal teeth (rare)

Head And Neck Eyes:
strabismus
long eyelashes
long palpebral fissure
arched eyebrows
sparse lateral eyebrows
more
Head And Neck Nose:
short columella
broad and/or depressed tip of nose

Head And Neck Mouth:
high-arched palate
cleft palate (rare)

Cardiovascular Heart:
congenital heart disease
atrial septal defect (in some patients)
atrioventricular septal defect (rare)
pulmonary valve stenosis (rare)
hypoplastic right ventricle (rare)

Skeletal Hands:
brachydactyly (in some patients)
persistent fetal fingertip pads

Growth Weight:
less than third centile

Cardiovascular Vascular:
aortic coarctation (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
behavioral difficulties

Clinical features from OMIM®:

300867 (Updated 20-May-2021)

UMLS symptoms related to Kabuki Syndrome 2:


seizures

Drugs & Therapeutics for Kabuki Syndrome 2

Search Clinical Trials , NIH Clinical Center for Kabuki Syndrome 2

Genetic Tests for Kabuki Syndrome 2

Genetic tests related to Kabuki Syndrome 2:

# Genetic test Affiliating Genes
1 Kabuki Syndrome 2 29 KDM6A

Anatomical Context for Kabuki Syndrome 2

MalaCards organs/tissues related to Kabuki Syndrome 2:

40
Eye, Heart

Publications for Kabuki Syndrome 2

Articles related to Kabuki Syndrome 2:

(show all 13)
# Title Authors PMID Year
1
Kabuki syndrome genes KMT2D and KDM6A: functional analyses demonstrate critical roles in craniofacial, heart and brain development. 6 57
25972376 2015
2
A three generation X-linked family with Kabuki syndrome phenotype and a frameshift mutation in KDM6A. 6 57
24664873 2014
3
MLL2 and KDM6A mutations in patients with Kabuki syndrome. 57 6
23913813 2013
4
KDM6A point mutations cause Kabuki syndrome. 57 6
23076834 2013
5
Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome. 57 6
22197486 2012
6
Persistent Hyperinsulinism in Kabuki Syndrome 2: Case Report and Literature Review. 6 61
27777708 2016
7
Kabuki syndrome: international consensus diagnostic criteria. 57
30514738 2019
8
Mutation Update for Kabuki Syndrome Genes KMT2D and KDM6A and Further Delineation of X-Linked Kabuki Syndrome Subtype 2. 6
27302555 2016
9
Clinical application of whole-exome sequencing across clinical indications. 6
26633542 2016
10
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 6
25741868 2015
11
Molecular analysis, pathogenic mechanisms, and readthrough therapy on a large cohort of Kabuki syndrome patients. 57
24633898 2014
12
Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. 57
7277096 1981
13
A fetus with Kabuki syndrome 2 detected by chromosomal microarray analysis. 61
32211113 2020

Variations for Kabuki Syndrome 2

ClinVar genetic disease variations for Kabuki Syndrome 2:

6 (show top 50) (show all 93)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 KDM6A nsv1067838 Deletion Pathogenic 29935 GRCh37: X:44866302-44912718
GRCh38: X:45007057-45053473
2 KDM6A NM_021140.3(KDM6A):c.3717G>A (p.Trp1239Ter) SNV Pathogenic 39992 rs398122929 GRCh37: X:44949156-44949156
GRCh38: X:45089911-45089911
3 KDM6A NM_021140.3(KDM6A):c.1555C>T (p.Arg519Ter) SNV Pathogenic 39993 rs397514628 GRCh37: X:44922694-44922694
GRCh38: X:45063449-45063449
4 KDM6A NM_021140.3(KDM6A):c.3351_3353TCT[1] (p.Leu1119del) Microsatellite Pathogenic 39994 rs398122829 GRCh37: X:44942771-44942773
GRCh38: X:45083526-45083528
5 KDM6A NM_021140.3(KDM6A):c.1909_1912del (p.Ser637fs) Deletion Pathogenic 91403 rs398122969 GRCh37: X:44923045-44923048
GRCh38: X:45063800-45063803
6 KDM6A NM_021140.3(KDM6A):c.2515_2518del (p.Asn839fs) Deletion Pathogenic 190247 rs786205676 GRCh37: X:44929412-44929415
GRCh38: X:45070167-45070170
7 KDM6A NM_021140.3(KDM6A):c.1543del (p.Val515fs) Deletion Pathogenic 211254 rs797045642 GRCh37: X:44922682-44922682
GRCh38: X:45063437-45063437
8 KDM6A NM_001291415.1(KDM6A):c.2988+1G>C SNV Pathogenic 431139 rs1135401809 GRCh37: X:44936072-44936072
GRCh38: X:45076827-45076827
9 KDM6A NM_021140.3(KDM6A):c.3016C>T (p.Gln1006Ter) SNV Pathogenic 471948 rs1556341546 GRCh37: X:44938468-44938468
GRCh38: X:45079223-45079223
10 KDM6A NM_021140.3(KDM6A):c.2462_2463del (p.Ser821fs) Deletion Pathogenic 539319 rs1556330304 GRCh37: X:44929362-44929363
GRCh38: X:45070117-45070118
11 KDM6A NM_021140.3(KDM6A):c.1392_1395TCAT[3] (p.Trp467fs) Microsatellite Pathogenic 559639 rs1556311265 GRCh37: X:44920630-44920631
GRCh38: X:45061385-45061386
12 KDM6A NM_021140.3(KDM6A):c.3763C>T (p.Arg1255Trp) SNV Pathogenic 565844 rs1450363794 GRCh37: X:44949994-44949994
GRCh38: X:45090749-45090749
13 KDM6A NM_021140.3(KDM6A):c.2832+1G>A SNV Pathogenic 545065 rs1135401809 GRCh37: X:44936072-44936072
GRCh38: X:45076827-45076827
14 KDM6A NM_021140.3(KDM6A):c.4051C>T (p.Arg1351Ter) SNV Pathogenic 644617 rs1318649487 GRCh37: X:44969369-44969369
GRCh38: X:45110124-45110124
15 KDM6A NM_001291415.2(KDM6A):c.493C>T (p.Arg165Ter) SNV Pathogenic 692010 rs912069418 GRCh37: X:44879904-44879904
GRCh38: X:45020659-45020659
16 KDM6A NM_001291415.2(KDM6A):c.3198del (p.Thr1067fs) Deletion Pathogenic 692059 rs1602928108 GRCh37: X:44938492-44938492
GRCh38: X:45079247-45079247
17 KDM6A NM_021140.3(KDM6A):c.2646_2647dup (p.Pro883fs) Duplication Pathogenic 637050 rs1602868720 GRCh37: X:44929545-44929546
GRCh38: X:45070300-45070301
18 KDM6A NM_021140.3(KDM6A):c.2101_2102TC[4] (p.His702fs) Microsatellite Pathogenic 471947 rs1556328781 GRCh37: X:44928999-44929000
GRCh38: X:45069754-45069755
19 KDM6A NM_001291415.2(KDM6A):c.2608del (p.Ser870fs) Deletion Pathogenic 861724 GRCh37: X:44929351-44929351
GRCh38: X:45070106-45070106
20 KDM6A NM_021140.3(KDM6A):c.2326_2329del (p.Asp776fs) Deletion Pathogenic 265212 rs886039398 GRCh37: X:44929224-44929227
GRCh38: X:45069979-45069982
21 KDM6A NM_001291415.2(KDM6A):c.140A>G (p.Glu47Gly) SNV Pathogenic 976704 GRCh37: X:44732937-44732937
GRCh38: X:44873691-44873691
22 KDM6A NM_001291415.2(KDM6A):c.875+1G>A SNV Pathogenic 981690 GRCh37: X:44913201-44913201
GRCh38: X:45053956-45053956
23 KDM6A NM_001291415.2(KDM6A):c.2002_2005del (p.Thr668fs) Microsatellite Pathogenic 981691 GRCh37: X:44922980-44922983
GRCh38: X:45063735-45063738
24 KDM6A NM_001291415.2(KDM6A):c.2230C>T (p.Gln744Ter) SNV Pathogenic 981692 GRCh37: X:44928974-44928974
GRCh38: X:45069729-45069729
25 KDM6A NM_001291415.2(KDM6A):c.3426_3429del (p.Ser1143fs) Deletion Pathogenic 981695 GRCh37: X:44942018-44942021
GRCh38: X:45082773-45082776
26 KDM6A NM_001291415.2(KDM6A):c.443+5G>C SNV Pathogenic 981696 GRCh37: X:44870269-44870269
GRCh38: X:45011024-45011024
27 KDM6A NM_001291415.2(KDM6A):c.514C>T (p.Arg172Ter) SNV Pathogenic 981697 GRCh37: X:44879925-44879925
GRCh38: X:45020680-45020680
28 KDM6A NM_001291415.2(KDM6A):c.564+1G>T SNV Pathogenic 981698 GRCh37: X:44879976-44879976
GRCh38: X:45020731-45020731
29 KDM6A NM_001291415.2(KDM6A):c.619+6T>C SNV Pathogenic 981699 GRCh37: X:44894236-44894236
GRCh38: X:45034991-45034991
30 KDM6A NM_001291415.2(KDM6A):c.620-2A>G SNV Pathogenic 981732 GRCh37: X:44896898-44896898
GRCh38: X:45037653-45037653
31 KDM6A NM_001291415.2(KDM6A):c.749-2A>G SNV Pathogenic 988776 GRCh37: X:44913072-44913072
GRCh38: X:45053827-45053827
32 KDM6A NM_001291415.2(KDM6A):c.1192C>T (p.Gln398Ter) SNV Pathogenic 984975 GRCh37: X:44918709-44918709
GRCh38: X:45059464-45059464
33 KDM6A NM_001291415.2(KDM6A):c.3058dup (p.Thr1020fs) Duplication Likely pathogenic 988751 GRCh37: X:44937713-44937714
GRCh38: X:45078468-45078469
34 KDM6A NM_021140.3(KDM6A):c.3835C>T (p.Arg1279Ter) SNV Likely pathogenic 216950 rs863224886 GRCh37: X:44950066-44950066
GRCh38: X:45090821-45090821
35 KDM6A NM_001291415.2(KDM6A):c.3590-2A>G SNV Likely pathogenic 981733 GRCh37: X:44945108-44945108
GRCh38: X:45085863-45085863
36 KDM6A NM_001291415.2(KDM6A):c.3095-1G>T SNV Likely pathogenic 981693 GRCh37: X:44938390-44938390
GRCh38: X:45079145-45079145
37 KDM6A NM_001291415.2(KDM6A):c.3229A>G (p.Ser1077Gly) SNV Likely pathogenic 981694 GRCh37: X:44938525-44938525
GRCh38: X:45079280-45079280
38 KDM6A NM_001291415.2(KDM6A):c.908C>A (p.Ala303Asp) SNV Likely pathogenic 976705 GRCh37: X:44918283-44918283
GRCh38: X:45059038-45059038
39 KDM6A NM_001291415.2(KDM6A):c.3409G>A (p.Gly1137Arg) SNV Likely pathogenic 979183 GRCh37: X:44942003-44942003
GRCh38: X:45082758-45082758
40 KDM6A NM_001291415.2(KDM6A):c.3301-2A>G SNV Likely pathogenic 964077 GRCh37: X:44941819-44941819
GRCh38: X:45082574-45082574
41 KDM6A NM_001291415.2(KDM6A):c.2519C>G (p.Ala840Gly) SNV Likely pathogenic 975571 GRCh37: X:44929263-44929263
GRCh38: X:45070018-45070018
42 KDM6A NM_021140.3(KDM6A):c.3736+2T>C SNV Likely pathogenic 183369 rs793888510 GRCh37: X:44949177-44949177
GRCh38: X:45089932-45089932
43 KDM6A NM_021140.3(KDM6A):c.752G>A (p.Trp251Ter) SNV Likely pathogenic 183368 rs793888509 GRCh37: X:44913077-44913077
GRCh38: X:45053832-45053832
44 overlap with 8 genes NC_000023.10:g.(?_43479884)_(45501849_?)del Deletion Likely pathogenic 183367 GRCh37: X:43479884-45501849
GRCh38:
45 overlap with 15 genes NC_000023.10:g.(?_43479884)_(46741003_?)del Deletion Likely pathogenic 183366 GRCh37: X:43479884-46741003
GRCh38:
46 KDM6A NM_021140.3(KDM6A):c.3144+1G>A SNV Likely pathogenic 663689 rs1602928572 GRCh37: X:44938597-44938597
GRCh38: X:45079352-45079352
47 KDM6A NM_021140.3(KDM6A):c.4161T>A (p.Tyr1387Ter) SNV Likely pathogenic 689653 rs1603068073 GRCh37: X:44969479-44969479
GRCh38: X:45110234-45110234
48 KDM6A NM_021140.3(KDM6A):c.3584C>T (p.Pro1195Leu) SNV Likely pathogenic 648826 rs1602985802 GRCh37: X:44949023-44949023
GRCh38: X:45089778-45089778
49 KDM6A NM_021140.3(KDM6A):c.1425+1G>T SNV Likely pathogenic 654686 rs1602799769 GRCh37: X:44920665-44920665
GRCh38: X:45061420-45061420
50 KDM6A NM_021140.3(KDM6A):c.3458G>A (p.Cys1153Tyr) SNV Likely pathogenic 545087 rs1556350571 GRCh37: X:44945134-44945134
GRCh38: X:45085889-45085889

Expression for Kabuki Syndrome 2

Search GEO for disease gene expression data for Kabuki Syndrome 2.

Pathways for Kabuki Syndrome 2

GO Terms for Kabuki Syndrome 2

Sources for Kabuki Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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