KLEFS1
MCID: KLF004
MIFTS: 33

Kleefstra Syndrome 1 (KLEFS1)

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

Aliases & Classifications for Kleefstra Syndrome 1

MalaCards integrated aliases for Kleefstra Syndrome 1:

Name: Kleefstra Syndrome 1 58 76
Chromosome 9q34.3 Deletion Syndrome 58 76
9q Subtelomeric Deletion Syndrome 58 60
Kleefstra Syndrome 60 74
9q- Syndrome 58 76
Klefs1 58 76
Kleefstra Syndrome Due to 9q Subtelomeric Deletion 60
Kleefstra Syndrome Due to 9q34 Microdeletion 60
Chromosome 9q Subtelomeric Deletion Syndrome 76
Kleefstra Syndrome Due to Monosomy 9q34 60
Kleefstra Syndrome Due to Del(9)(q34) 60
9qstds 60

Characteristics:

Orphanet epidemiological data:

60
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:

58
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:

33
kleefstra syndrome 1:
Inheritance autosomal dominant inheritance sporadic


Classifications:



Summaries for Kleefstra Syndrome 1

OMIM : 58 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 due to a point mutation and kleefstra syndrome, 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 hypertelorism and intellectual disability

UniProtKB/Swiss-Prot : 76 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:

(show all 20)
# Related Disease Score Top Affiliating Genes
1 kleefstra syndrome due to a point mutation 12.1
2 kleefstra syndrome 11.4
3 kleefstra syndrome 2 11.1
4 autism 10.2
5 exophthalmos 10.2
6 hypopituitarism 10.2
7 chromosomal triplication 10.0
8 chromosome 9q duplication 10.0
9 hypoplastic left heart syndrome 1 10.0
10 valproate embryopathy 10.0
11 pulmonary hypertension 10.0
12 hypoplastic left heart syndrome 10.0
13 apraxia 10.0
14 hypogonadotropic hypogonadism 10.0
15 hypogonadism 10.0
16 hypogonadotropism 10.0
17 childhood apraxia of speech 10.0
18 hypotonia 10.0
19 tooth agenesis 9.9
20 xq12-q13.3 duplication syndrome 9.9

Graphical network of the top 20 diseases related to Kleefstra Syndrome 1:



Diseases related to Kleefstra Syndrome 1

Symptoms & Phenotypes for Kleefstra Syndrome 1

Human phenotypes related to Kleefstra Syndrome 1:

60 33 (show top 50) (show all 110)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 60 33 frequent (33%) Very frequent (99-80%),Very frequent (99-80%) HP:0000316
2 intellectual disability 60 33 hallmark (90%) Very frequent (99-80%) HP:0001249
3 muscular hypotonia 60 33 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001252
4 dysphasia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002357
5 global developmental delay 60 33 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001263
6 short nose 60 33 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0003196
7 anteverted nares 60 33 frequent (33%) Very frequent (99-80%),Very frequent (99-80%) HP:0000463
8 brachycephaly 60 33 frequent (33%) Frequent (79-30%),Very frequent (99-80%) HP:0000248
9 everted lower lip vermilion 60 33 frequent (33%) Very frequent (99-80%),Very frequent (99-80%) HP:0000232
10 specific learning disability 60 33 hallmark (90%) Very frequent (99-80%) HP:0001328
11 aphasia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002381
12 flat occiput 60 33 hallmark (90%) Very frequent (99-80%) HP:0005469
13 highly arched eyebrow 60 33 hallmark (90%) Frequent (79-30%),Very frequent (99-80%) HP:0002553
14 echolalia 60 33 hallmark (90%) Very frequent (99-80%) HP:0010529
15 mutism 60 33 hallmark (90%) Very frequent (99-80%) HP:0002300
16 malar flattening 60 33 frequent (33%) Very frequent (99-80%) HP:0000272
17 obesity 60 33 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0001513
18 sleep disturbance 60 33 frequent (33%) Frequent (79-30%),Occasional (29-5%) HP:0002360
19 macroglossia 60 33 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0000158
20 coarse facial features 60 33 frequent (33%) Very frequent (99-80%) HP:0000280
21 mandibular prognathia 60 33 frequent (33%) Frequent (79-30%) HP:0000303
22 recurrent respiratory infections 60 33 frequent (33%) Occasional (29-5%) HP:0002205
23 delayed speech and language development 60 33 frequent (33%) Very frequent (99-80%) HP:0000750
24 microcephaly 60 33 very rare (1%) Frequent (79-30%),Frequent (79-30%) HP:0000252
25 stereotypy 60 33 frequent (33%) Occasional (29-5%) HP:0000733
26 cryptorchidism 60 33 frequent (33%) Occasional (29-5%),Frequent (79-30%) HP:0000028
27 autism 60 33 frequent (33%) Frequent (79-30%) HP:0000717
28 hypospadias 60 33 frequent (33%) Occasional (29-5%) HP:0000047
29 absence seizure 60 33 frequent (33%) Frequent (79-30%) HP:0002121
30 aggressive behavior 60 33 frequent (33%) Frequent (79-30%) HP:0000718
31 status epilepticus 60 33 frequent (33%) Frequent (79-30%) HP:0002133
32 upslanted palpebral fissure 60 33 frequent (33%) Frequent (79-30%) HP:0000582
33 downturned corners of mouth 60 33 frequent (33%) Occasional (29-5%),Frequent (79-30%) HP:0002714
34 protruding tongue 60 33 frequent (33%) Frequent (79-30%) HP:0010808
35 midface retrusion 60 33 frequent (33%) Frequent (79-30%) HP:0011800
36 synophrys 60 33 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0000664
37 micropenis 60 33 frequent (33%) Occasional (29-5%) HP:0000054
38 epileptic spasms 60 33 frequent (33%) Frequent (79-30%) HP:0011097
39 abnormality of the pinna 33 frequent (33%) HP:0000377
40 u-shaped upper lip vermilion 33 frequent (33%) HP:0010806
41 abnormal cardiac septum morphology 33 frequent (33%) HP:0001671
42 agenesis of corpus callosum 60 33 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001274
43 depressivity 60 33 occasional (7.5%) Occasional (29-5%) HP:0000716
44 failure to thrive 60 33 occasional (7.5%) Occasional (29-5%) HP:0001508
45 inguinal hernia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000023
46 hearing impairment 60 33 very rare (1%) Frequent (79-30%),Occasional (29-5%) HP:0000365
47 gastroesophageal reflux 60 33 occasional (7.5%) Occasional (29-5%) HP:0002020
48 renal insufficiency 60 33 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0000083
49 irritability 60 33 occasional (7.5%) Occasional (29-5%) HP:0000737
50 feeding difficulties 60 33 occasional (7.5%) Occasional (29-5%) HP:0011968

Symptoms via clinical synopsis from OMIM:

58
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

Skeletal Hands:
brachydactyly
single transverse palmar creases

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

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

Skin Nails Hair Hair:
synophrys

Cardiovascular Heart:
conotruncal heart defects

Clinical features from OMIM:

610253

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:

42
Heart, Tongue, Testis, Eye

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:

76
# 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 496)
# 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 rs1554896943 GRCh37 Chromosome 9, 140708803: 140708935
10 EHMT1 NM_024757.4(EHMT1): c.3181-80_3233del deletion Pathogenic rs1554896943 GRCh38 Chromosome 9, 137814351: 137814483
11 EHMT1 NM_024757.4(EHMT1): c.1044G> A (p.Ser348=) single nucleotide variant Benign rs1129767 GRCh37 Chromosome 9, 140638416: 140638416
12 EHMT1 NM_024757.4(EHMT1): c.1044G> A (p.Ser348=) single nucleotide variant Benign rs1129767 GRCh38 Chromosome 9, 137743964: 137743964
13 EHMT1 NM_024757.4(EHMT1): c.1089T> C (p.Gly363=) single nucleotide variant Benign rs1129768 GRCh37 Chromosome 9, 140638461: 140638461
14 EHMT1 NM_024757.4(EHMT1): c.1089T> C (p.Gly363=) single nucleotide variant Benign rs1129768 GRCh38 Chromosome 9, 137744009: 137744009
15 EHMT1 NM_024757.4(EHMT1): c.1368C> T (p.Leu456=) single nucleotide variant Benign rs45450992 GRCh37 Chromosome 9, 140648742: 140648742
16 EHMT1 NM_024757.4(EHMT1): c.1368C> T (p.Leu456=) single nucleotide variant Benign rs45450992 GRCh38 Chromosome 9, 137754290: 137754290
17 EHMT1 NM_024757.4(EHMT1): c.1533_1536del (p.Asp512Alafs) deletion Pathogenic rs137852716 GRCh37 Chromosome 9, 140657158: 140657161
18 EHMT1 NM_024757.4(EHMT1): c.1533_1536del (p.Asp512Alafs) deletion Pathogenic rs137852716 GRCh38 Chromosome 9, 137762706: 137762709
19 EHMT1 NM_024757.4(EHMT1): c.1810C> T (p.Gln604Ter) single nucleotide variant Pathogenic rs137852717 GRCh37 Chromosome 9, 140671088: 140671088
20 EHMT1 NM_024757.4(EHMT1): c.1810C> T (p.Gln604Ter) single nucleotide variant Pathogenic rs137852717 GRCh38 Chromosome 9, 137776636: 137776636
21 EHMT1 NM_024757.4(EHMT1): c.1858C> T (p.Arg620Ter) single nucleotide variant Pathogenic rs137852718 GRCh37 Chromosome 9, 140671136: 140671136
22 EHMT1 NM_024757.4(EHMT1): c.1858C> T (p.Arg620Ter) single nucleotide variant Pathogenic rs137852718 GRCh38 Chromosome 9, 137776684: 137776684
23 EHMT1 NM_024757.4(EHMT1): c.2028dup (p.Pro677Alafs) duplication Pathogenic rs1554879411 GRCh37 Chromosome 9, 140672343: 140672343
24 EHMT1 NM_024757.4(EHMT1): c.2028dup (p.Pro677Alafs) duplication Pathogenic rs1554879411 GRCh38 Chromosome 9, 137777891: 137777891
25 EHMT1 NM_024757.4(EHMT1): c.2193-1G> C single nucleotide variant Pathogenic rs137852720 GRCh37 Chromosome 9, 140674086: 140674086
26 EHMT1 NM_024757.4(EHMT1): c.2193-1G> C single nucleotide variant Pathogenic rs137852720 GRCh38 Chromosome 9, 137779634: 137779634
27 EHMT1 NM_024757.4(EHMT1): c.2863_2864delGT (p.Val955Argfs) deletion Pathogenic rs137852721 GRCh37 Chromosome 9, 140706063: 140706064
28 EHMT1 NM_024757.4(EHMT1): c.2863_2864delGT (p.Val955Argfs) deletion Pathogenic rs137852721 GRCh38 Chromosome 9, 137811611: 137811612
29 EHMT1 NM_024757.4(EHMT1): c.2868-1G> A single nucleotide variant Pathogenic rs137852722 GRCh37 Chromosome 9, 140707457: 140707457
30 EHMT1 NM_024757.4(EHMT1): c.2868-1G> A single nucleotide variant Pathogenic rs137852722 GRCh38 Chromosome 9, 137813005: 137813005
31 EHMT1 NM_024757.4(EHMT1): c.2877_2880delTTCT (p.Ser960Glyfs) deletion Pathogenic rs786205129 GRCh37 Chromosome 9, 140707467: 140707470
32 EHMT1 NM_024757.4(EHMT1): c.2877_2880delTTCT (p.Ser960Glyfs) deletion Pathogenic rs786205129 GRCh38 Chromosome 9, 137813015: 137813018
33 EHMT1 NM_024757.4(EHMT1): c.3180+1G> T single nucleotide variant Pathogenic rs137852724 GRCh37 Chromosome 9, 140707983: 140707983
34 EHMT1 NM_024757.4(EHMT1): c.3180+1G> T single nucleotide variant Pathogenic rs137852724 GRCh38 Chromosome 9, 137813531: 137813531
35 EHMT1 NM_024757.4(EHMT1): c.3229C> T (p.Gln1077Ter) single nucleotide variant Pathogenic rs137852725 GRCh37 Chromosome 9, 140708931: 140708931
36 EHMT1 NM_024757.4(EHMT1): c.3229C> T (p.Gln1077Ter) single nucleotide variant Pathogenic rs137852725 GRCh38 Chromosome 9, 137814479: 137814479
37 EHMT1 NM_024757.4(EHMT1): c.3589C> T (p.Arg1197Trp) single nucleotide variant Likely pathogenic rs137852727 GRCh37 Chromosome 9, 140728849: 140728849
38 EHMT1 NM_024757.4(EHMT1): c.3589C> T (p.Arg1197Trp) single nucleotide variant Likely pathogenic rs137852727 GRCh38 Chromosome 9, 137834397: 137834397
39 EHMT1 NM_024757.4(EHMT1): c.444T> C (p.Pro148=) single nucleotide variant Benign rs3812497 GRCh37 Chromosome 9, 140611436: 140611436
40 EHMT1 NM_024757.4(EHMT1): c.444T> C (p.Pro148=) single nucleotide variant Benign rs3812497 GRCh38 Chromosome 9, 137716984: 137716984
41 NR1I3 NM_001077482.2(NR1I3): c.740T> C (p.Phe247Ser) single nucleotide variant Uncertain significance rs398122411 GRCh37 Chromosome 1, 161200990: 161200990
42 NR1I3 NM_001077482.2(NR1I3): c.740T> C (p.Phe247Ser) single nucleotide variant Uncertain significance rs398122411 GRCh38 Chromosome 1, 161231200: 161231200
43 EHMT1 NM_024757.4(EHMT1): c.128C> G (p.Ala43Gly) single nucleotide variant Benign rs79514677 GRCh37 Chromosome 9, 140611120: 140611120
44 EHMT1 NM_024757.4(EHMT1): c.128C> G (p.Ala43Gly) single nucleotide variant Benign rs79514677 GRCh38 Chromosome 9, 137716668: 137716668
45 EHMT1 NM_024757.4(EHMT1): c.129A> T (p.Ala43=) single nucleotide variant Benign rs76684726 GRCh37 Chromosome 9, 140611121: 140611121
46 EHMT1 NM_024757.4(EHMT1): c.129A> T (p.Ala43=) single nucleotide variant Benign rs76684726 GRCh38 Chromosome 9, 137716669: 137716669
47 EHMT1 NM_024757.4(EHMT1): c.1369+9C> T single nucleotide variant Conflicting interpretations of pathogenicity rs146125583 GRCh37 Chromosome 9, 140648752: 140648752
48 EHMT1 NM_024757.4(EHMT1): c.1369+9C> T single nucleotide variant Conflicting interpretations of pathogenicity rs146125583 GRCh38 Chromosome 9, 137754300: 137754300
49 EHMT1 NM_024757.4(EHMT1): c.1501+13G> T single nucleotide variant Benign rs3125794 GRCh37 Chromosome 9, 140652476: 140652476
50 EHMT1 NM_024757.4(EHMT1): c.1501+13G> T single nucleotide variant Benign rs3125794 GRCh38 Chromosome 9, 137758024: 137758024

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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