MCID: KLF004
MIFTS: 30

Kleefstra Syndrome 1

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

Aliases & Classifications for Kleefstra Syndrome 1

MalaCards integrated aliases for Kleefstra Syndrome 1:

Name: Kleefstra Syndrome 1 57 75
Chromosome 9q34.3 Deletion Syndrome 57 75
9q Subtelomeric Deletion Syndrome 57 59
Kleefstra Syndrome 59 73
9q- Syndrome 57 75
Klefs1 57 75
Kleefstra Syndrome Due to 9q Subtelomeric Deletion 59
Kleefstra Syndrome Due to 9q34 Microdeletion 59
Chromosome 9q Subtelomeric Deletion Syndrome 75
Kleefstra Syndrome Due to Monosomy 9q34 59
Kleefstra Syndrome Due to Del(9)(q34) 59
9qstds 59

Characteristics:

Orphanet epidemiological data:

59
kleefstra syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: elderly;
kleefstra syndrome due to 9q34 microdeletion
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
de novo mutation in most cases
many cases have submicroscopic subtelomeric deletions of chromosome 9q leading to haploinsufficiency of ehmt1


HPO:

32
kleefstra syndrome 1:
Inheritance autosomal dominant inheritance sporadic


Classifications:



Summaries for Kleefstra Syndrome 1

OMIM : 57 Submicroscopic subtelomeric deletions of chromosome 9q are associated with a recognizable mental retardation syndrome (Harada et al., 2004; Iwakoshi et al., 2004; Stewart et al., 2004; Neas et al., 2005). Common features in patients with 9q subtelomeric deletion syndrome are severe mental retardation, hypotonia, brachy(micro)cephaly, epileptic seizures, flat face with hypertelorism, synophrys, anteverted nares, everted lower lip, carp mouth with macroglossia, and heart defects. (610253)

MalaCards based summary : Kleefstra Syndrome 1, also known as chromosome 9q34.3 deletion syndrome, is related to kleefstra syndrome and kleefstra syndrome 2, and has symptoms including seizures An important gene associated with Kleefstra Syndrome 1 is EHMT1 (Euchromatic Histone Lysine Methyltransferase 1). Affiliated tissues include heart, tongue and testis, and related phenotypes are malar flattening and hypertelorism

UniProtKB/Swiss-Prot : 75 Kleefstra syndrome 1: A form of Kleefstra syndrome, an autosomal dominant disease characterized by variable mental retardation, psychomotor developmental delay, seizures, behavioral abnormalities, and facial dysmorphisms. KLEFS1 patients additionally manifest brachy(micro)cephaly, congenital heart defects, and urogenital defects.

Related Diseases for Kleefstra Syndrome 1

Diseases in the Kleefstra Syndrome family:

Kleefstra Syndrome 1 Kleefstra Syndrome 2
Kleefstra Syndrome Due to a Point Mutation

Diseases related to Kleefstra Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 kleefstra syndrome 11.3
2 kleefstra syndrome 2 10.9

Symptoms & Phenotypes for Kleefstra Syndrome 1

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
synophrys
upslanting palpebral fissures

Neurologic Central Nervous System:
seizures
hypotonia
mental retardation, severe

Head And Neck Head:
microcephaly
brachycephaly

Head And Neck Face:
flat face
midface hypoplasia
prognathism
coarse facies

Neurologic Behavioral Psychiatric Manifestations:
aggressive behavior
stereotypic movements
behavioral problems
obsessive-compulsive disorder
sleep disorders

Head And Neck Ears:
hearing loss
malformed ears

Growth Weight:
obesity

Head And Neck Mouth:
macroglossia
everted lower lip
carp-shaped mouth

Head And Neck Nose:
anteverted nares

Skeletal Hands:
brachydactyly
single transverse palmar creases

Skin Nails Hair Hair:
synophrys

Cardiovascular Heart:
conotruncal heart defects


Clinical features from OMIM:

610253

Human phenotypes related to Kleefstra Syndrome 1:

59 32 (show top 50) (show all 110)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 malar flattening 59 32 frequent (33%) Very frequent (99-80%) HP:0000272
2 hypertelorism 59 32 frequent (33%) Very frequent (99-80%),Very frequent (99-80%) HP:0000316
3 agenesis of corpus callosum 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001274
4 obesity 59 32 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0001513
5 depressivity 59 32 occasional (7.5%) Occasional (29-5%) HP:0000716
6 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
7 seizures 59 32 very rare (1%) Occasional (29-5%),Frequent (79-30%) HP:0001250
8 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001252
9 failure to thrive 59 32 occasional (7.5%) Occasional (29-5%) HP:0001508
10 dysphasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002357
11 sleep disturbance 59 32 frequent (33%) Frequent (79-30%),Occasional (29-5%) HP:0002360
12 inguinal hernia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000023
13 macroglossia 59 32 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0000158
14 coarse facial features 59 32 frequent (33%) Very frequent (99-80%) HP:0000280
15 mandibular prognathia 59 32 frequent (33%) Frequent (79-30%) HP:0000303
16 hearing impairment 59 32 very rare (1%) Frequent (79-30%),Occasional (29-5%) HP:0000365
17 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001263
18 recurrent respiratory infections 59 32 frequent (33%) Occasional (29-5%) HP:0002205
19 delayed speech and language development 59 32 frequent (33%) Very frequent (99-80%) HP:0000750
20 short nose 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0003196
21 microcephaly 59 32 very rare (1%) Frequent (79-30%),Frequent (79-30%) HP:0000252
22 anteverted nares 59 32 frequent (33%) Very frequent (99-80%),Very frequent (99-80%) HP:0000463
23 gastroesophageal reflux 59 32 occasional (7.5%) Occasional (29-5%) HP:0002020
24 renal insufficiency 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0000083
25 stereotypy 59 32 frequent (33%) Occasional (29-5%) HP:0000733
26 brachycephaly 59 32 frequent (33%) Frequent (79-30%),Very frequent (99-80%) HP:0000248
27 intellectual disability, severe 59 32 Very frequent (99-80%) HP:0010864
28 irritability 59 32 occasional (7.5%) Occasional (29-5%) HP:0000737
29 feeding difficulties 59 32 occasional (7.5%) Occasional (29-5%) HP:0011968
30 everted lower lip vermilion 59 32 frequent (33%) Very frequent (99-80%),Very frequent (99-80%) HP:0000232
31 cryptorchidism 59 32 frequent (33%) Occasional (29-5%),Frequent (79-30%) HP:0000028
32 autism 59 32 frequent (33%) Frequent (79-30%) HP:0000717
33 growth delay 59 32 occasional (7.5%) Occasional (29-5%) HP:0001510
34 anxiety 59 32 occasional (7.5%) Occasional (29-5%) HP:0000739
35 specific learning disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001328
36 coarctation of aorta 59 32 occasional (7.5%) Frequent (79-30%),Occasional (29-5%) HP:0001680
37 ventriculomegaly 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0002119
38 aphasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002381
39 hypospadias 59 32 frequent (33%) Occasional (29-5%) HP:0000047
40 absence seizures 59 32 frequent (33%) Frequent (79-30%) HP:0002121
41 upslanted palpebral fissure 59 32 frequent (33%) Frequent (79-30%) HP:0000582
42 downturned corners of mouth 59 32 frequent (33%) Occasional (29-5%),Frequent (79-30%) HP:0002714
43 protruding tongue 59 32 frequent (33%) Frequent (79-30%) HP:0010808
44 vesicoureteral reflux 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0000076
45 tetralogy of fallot 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001636
46 talipes equinovarus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001762
47 flat occiput 59 32 hallmark (90%) Very frequent (99-80%) HP:0005469
48 hypoplasia of penis 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0008736
49 aggressive behavior 59 32 frequent (33%) Frequent (79-30%) HP:0000718
50 midface retrusion 59 32 frequent (33%) Frequent (79-30%) HP:0011800

UMLS symptoms related to Kleefstra Syndrome 1:


seizures

Drugs & Therapeutics for Kleefstra Syndrome 1

Search Clinical Trials , NIH Clinical Center for Kleefstra Syndrome 1

Genetic Tests for Kleefstra Syndrome 1

Anatomical Context for Kleefstra Syndrome 1

MalaCards organs/tissues related to Kleefstra Syndrome 1:

41
Heart, Tongue, Testis

Publications for Kleefstra Syndrome 1

Articles related to Kleefstra Syndrome 1:

# Title Authors Year
1
Further clinical and molecular delineation of the 9q subtelomeric deletion syndrome supports a major contribution of EHMT1 haploinsufficiency to the core phenotype. ( 19264732 )
2009
2
A cryptic unbalanced translocation t(2;9)(p25.2;q34.3) causes the phenotype of 9q subtelomeric deletion syndrome and additional exophthalmos and joint contractures. ( 18674647 )
2008

Variations for Kleefstra Syndrome 1

UniProtKB/Swiss-Prot genetic disease variations for Kleefstra Syndrome 1:

75
# Symbol AA change Variation ID SNP ID
1 EHMT1 p.Cys1075Tyr VAR_069183

ClinVar genetic disease variations for Kleefstra Syndrome 1:

6
(show top 50) (show all 334)
# Gene Variation Type Significance SNP ID Assembly Location
1 EHMT1 NM_024757.4(EHMT1): c.3502C> T (p.Arg1168Ter) single nucleotide variant Pathogenic rs121918301 GRCh37 Chromosome 9, 140712552: 140712552
2 EHMT1 NM_024757.4(EHMT1): c.3502C> T (p.Arg1168Ter) single nucleotide variant Pathogenic rs121918301 GRCh38 Chromosome 9, 137818100: 137818100
3 EHMT1 NM_024757.4(EHMT1): c.1413_1425delGGCACCAGGAGAC (p.Pro473Glnfs) deletion Pathogenic rs137852715 GRCh37 Chromosome 9, 140652375: 140652387
4 EHMT1 NM_024757.4(EHMT1): c.1413_1425delGGCACCAGGAGAC (p.Pro473Glnfs) deletion Pathogenic rs137852715 GRCh38 Chromosome 9, 137757923: 137757935
5 EHMT1 NM_024757.4(EHMT1): c.3218G> A (p.Cys1073Tyr) single nucleotide variant Pathogenic rs137852726 GRCh37 Chromosome 9, 140708920: 140708920
6 EHMT1 NM_024757.4(EHMT1): c.3218G> A (p.Cys1073Tyr) single nucleotide variant Pathogenic rs137852726 GRCh38 Chromosome 9, 137814468: 137814468
7 EHMT1 NM_024757.4(EHMT1): c.871C> T (p.Arg291Ter) single nucleotide variant Pathogenic rs137852714 GRCh37 Chromosome 9, 140637870: 140637870
8 EHMT1 NM_024757.4(EHMT1): c.871C> T (p.Arg291Ter) single nucleotide variant Pathogenic rs137852714 GRCh38 Chromosome 9, 137743418: 137743418
9 EHMT1 NM_024757.4(EHMT1): c.3181-80_3233del deletion Pathogenic GRCh37 Chromosome 9, 140708803: 140708935
10 EHMT1 NM_024757.4(EHMT1): c.3181-80_3233del deletion Pathogenic GRCh38 Chromosome 9, 137814351: 137814483
11 EHMT1 NM_024757.4(EHMT1): c.1533_1536delAGAC (p.Asp512Alafs) deletion Pathogenic rs137852716 GRCh37 Chromosome 9, 140657158: 140657161
12 EHMT1 NM_024757.4(EHMT1): c.1533_1536delAGAC (p.Asp512Alafs) deletion Pathogenic rs137852716 GRCh38 Chromosome 9, 137762706: 137762709
13 EHMT1 NM_024757.4(EHMT1): c.1810C> T (p.Gln604Ter) single nucleotide variant Pathogenic rs137852717 GRCh37 Chromosome 9, 140671088: 140671088
14 EHMT1 NM_024757.4(EHMT1): c.1810C> T (p.Gln604Ter) single nucleotide variant Pathogenic rs137852717 GRCh38 Chromosome 9, 137776636: 137776636
15 EHMT1 NM_024757.4(EHMT1): c.1858C> T (p.Arg620Ter) single nucleotide variant Pathogenic rs137852718 GRCh37 Chromosome 9, 140671136: 140671136
16 EHMT1 NM_024757.4(EHMT1): c.1858C> T (p.Arg620Ter) single nucleotide variant Pathogenic rs137852718 GRCh38 Chromosome 9, 137776684: 137776684
17 EHMT1 NM_024757.4(EHMT1): c.2028dupG (p.Pro677Alafs) duplication Pathogenic rs786205128 GRCh37 Chromosome 9, 140672343: 140672343
18 EHMT1 NM_024757.4(EHMT1): c.2028dupG (p.Pro677Alafs) duplication Pathogenic rs786205128 GRCh38 Chromosome 9, 137777891: 137777891
19 EHMT1 NM_024757.4(EHMT1): c.2193-1G> C single nucleotide variant Pathogenic rs137852720 GRCh37 Chromosome 9, 140674086: 140674086
20 EHMT1 NM_024757.4(EHMT1): c.2193-1G> C single nucleotide variant Pathogenic rs137852720 GRCh38 Chromosome 9, 137779634: 137779634
21 EHMT1 NM_024757.4(EHMT1): c.2863_2864delGT (p.Val955Argfs) deletion Pathogenic rs137852721 GRCh37 Chromosome 9, 140706063: 140706064
22 EHMT1 NM_024757.4(EHMT1): c.2863_2864delGT (p.Val955Argfs) deletion Pathogenic rs137852721 GRCh38 Chromosome 9, 137811611: 137811612
23 EHMT1 NM_024757.4(EHMT1): c.2868-1G> A single nucleotide variant Pathogenic rs137852722 GRCh37 Chromosome 9, 140707457: 140707457
24 EHMT1 NM_024757.4(EHMT1): c.2868-1G> A single nucleotide variant Pathogenic rs137852722 GRCh38 Chromosome 9, 137813005: 137813005
25 EHMT1 NM_024757.4(EHMT1): c.2877_2880delTTCT (p.Ser960Glyfs) deletion Pathogenic rs786205129 GRCh37 Chromosome 9, 140707467: 140707470
26 EHMT1 NM_024757.4(EHMT1): c.2877_2880delTTCT (p.Ser960Glyfs) deletion Pathogenic rs786205129 GRCh38 Chromosome 9, 137813015: 137813018
27 EHMT1 NM_024757.4(EHMT1): c.3180+1G> T single nucleotide variant Pathogenic rs137852724 GRCh37 Chromosome 9, 140707983: 140707983
28 EHMT1 NM_024757.4(EHMT1): c.3180+1G> T single nucleotide variant Pathogenic rs137852724 GRCh38 Chromosome 9, 137813531: 137813531
29 EHMT1 NM_024757.4(EHMT1): c.3229C> T (p.Gln1077Ter) single nucleotide variant Pathogenic rs137852725 GRCh37 Chromosome 9, 140708931: 140708931
30 EHMT1 NM_024757.4(EHMT1): c.3229C> T (p.Gln1077Ter) single nucleotide variant Pathogenic rs137852725 GRCh38 Chromosome 9, 137814479: 137814479
31 EHMT1 NM_024757.4(EHMT1): c.3589C> T (p.Arg1197Trp) single nucleotide variant Pathogenic rs137852727 GRCh37 Chromosome 9, 140728849: 140728849
32 EHMT1 NM_024757.4(EHMT1): c.3589C> T (p.Arg1197Trp) single nucleotide variant Pathogenic rs137852727 GRCh38 Chromosome 9, 137834397: 137834397
33 EHMT1 NM_024757.4(EHMT1): c.480C> T (p.Gly160=) single nucleotide variant Benign/Likely benign rs150135875 GRCh37 Chromosome 9, 140611472: 140611472
34 EHMT1 NM_024757.4(EHMT1): c.480C> T (p.Gly160=) single nucleotide variant Benign/Likely benign rs150135875 GRCh38 Chromosome 9, 137717020: 137717020
35 EHMT1 NM_024757.4(EHMT1): c.2040G> A (p.Ser680=) single nucleotide variant Benign rs150451099 GRCh37 Chromosome 9, 140672355: 140672355
36 EHMT1 NM_024757.4(EHMT1): c.2040G> A (p.Ser680=) single nucleotide variant Benign rs150451099 GRCh38 Chromosome 9, 137777903: 137777903
37 EHMT1 NM_024757.4(EHMT1): c.2595C> T (p.Asp865=) single nucleotide variant Conflicting interpretations of pathogenicity rs780742937 GRCh37 Chromosome 9, 140693354: 140693354
38 EHMT1 NM_024757.4(EHMT1): c.2595C> T (p.Asp865=) single nucleotide variant Conflicting interpretations of pathogenicity rs780742937 GRCh38 Chromosome 9, 137798902: 137798902
39 EHMT1 NM_024757.4(EHMT1): c.2695A> G (p.Ile899Val) single nucleotide variant Conflicting interpretations of pathogenicity rs144085805 GRCh37 Chromosome 9, 140695419: 140695419
40 EHMT1 NM_024757.4(EHMT1): c.2695A> G (p.Ile899Val) single nucleotide variant Conflicting interpretations of pathogenicity rs144085805 GRCh38 Chromosome 9, 137800967: 137800967
41 EHMT1 NM_024757.4(EHMT1): c.3011G> A (p.Ser1004Asn) single nucleotide variant Benign/Likely benign rs138283222 GRCh37 Chromosome 9, 140707601: 140707601
42 EHMT1 NM_024757.4(EHMT1): c.3011G> A (p.Ser1004Asn) single nucleotide variant Benign/Likely benign rs138283222 GRCh38 Chromosome 9, 137813149: 137813149
43 EHMT1 NM_024757.4(EHMT1): c.581C> T (p.Pro194Leu) single nucleotide variant Benign rs35570782 GRCh37 Chromosome 9, 140611573: 140611573
44 EHMT1 NM_024757.4(EHMT1): c.581C> T (p.Pro194Leu) single nucleotide variant Benign rs35570782 GRCh38 Chromosome 9, 137717121: 137717121
45 EHMT1 NM_024757.4(EHMT1): c.183C> T (p.Ser61=) single nucleotide variant Conflicting interpretations of pathogenicity rs774448433 GRCh37 Chromosome 9, 140611175: 140611175
46 EHMT1 NM_024757.4(EHMT1): c.183C> T (p.Ser61=) single nucleotide variant Conflicting interpretations of pathogenicity rs774448433 GRCh38 Chromosome 9, 137716723: 137716723
47 EHMT1 NM_024757.4(EHMT1): c.737G> A (p.Arg246Gln) single nucleotide variant Likely benign rs144871446 GRCh37 Chromosome 9, 140622895: 140622895
48 EHMT1 NM_024757.4(EHMT1): c.737G> A (p.Arg246Gln) single nucleotide variant Likely benign rs144871446 GRCh38 Chromosome 9, 137728443: 137728443
49 EHMT1 NM_024757.4(EHMT1): c.391delG (p.Ala131Profs) deletion Pathogenic rs797045043 GRCh37 Chromosome 9, 140611383: 140611383
50 EHMT1 NM_024757.4(EHMT1): c.391delG (p.Ala131Profs) deletion Pathogenic rs797045043 GRCh38 Chromosome 9, 137716931: 137716931

Expression for Kleefstra Syndrome 1

Search GEO for disease gene expression data for Kleefstra Syndrome 1.

Pathways for Kleefstra Syndrome 1

GO Terms for Kleefstra Syndrome 1

Sources for Kleefstra Syndrome 1

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