SCKL1
MCID: SCK009
MIFTS: 47

Seckel Syndrome 1 (SCKL1)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases, Smell/Taste diseases

Aliases & Classifications for Seckel Syndrome 1

MalaCards integrated aliases for Seckel Syndrome 1:

Name: Seckel Syndrome 1 57 12 75 29 13 6 15
Microcephalic Primordial Dwarfism I 57 12 75
Sckl1 57 12 75
Nanocephalic Dwarfism 57 75
Seckel-Type Dwarfism 57 75
Bird-Headed Dwarfism 57 75
Seckel Syndrome, Type 1 40
Seckel Syndrome 73
Sckl 57

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
half of cases show retarded head circumference equal to height retardation
other half show head circumference more retarded than height


HPO:

32
seckel syndrome 1:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Seckel Syndrome 1

UniProtKB/Swiss-Prot : 75 Seckel syndrome 1: A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation.

MalaCards based summary : Seckel Syndrome 1, also known as microcephalic primordial dwarfism i, is related to seckel syndrome and seckel syndrome 2, and has symptoms including seizures An important gene associated with Seckel Syndrome 1 is ATR (ATR Serine/Threonine Kinase), and among its related pathways/superpathways are Gene Expression and DNA Double-Strand Break Repair. Affiliated tissues include bone and eye, and related phenotypes are low-set ears and high palate

Disease Ontology : 12 A Seckel syndrome that has material basis in homozygous or compound heterozygous mutation in the ATR gene on chromosome 3q23.

OMIM : 57 Seckel syndrome is a rare autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance (Shanske et al., 1997). (210600)

Related Diseases for Seckel Syndrome 1

Diseases in the Seckel Syndrome family:

Seckel Syndrome 1 Seckel Syndrome 2
Seckel Syndrome 4 Seckel Syndrome 5
Seckel Syndrome 6 Seckel Syndrome 7
Seckel Syndrome 8 Seckel Syndrome 9
Seckel Syndrome 10

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

(show all 24)
# Related Disease Score Top Affiliating Genes
1 seckel syndrome 31.2 ATR CENPJ CEP152 RBBP8
2 seckel syndrome 2 30.9 ATR CENPJ CEP152 MNAT1 RBBP8
3 microcephaly 29.7 ATR CENPJ CEP152 RBBP8
4 microcephalic primordial dwarfism, montreal type 12.0
5 bangstad syndrome 11.6
6 seckel like syndrome majoor-krakauer type 11.5
7 seckel syndrome 8 11.1
8 isolated growth hormone deficiency, type ia 10.3
9 dwarfism 10.3
10 seckel syndrome 5 10.1 CENPJ CEP152
11 microcephaly 3, primary, autosomal recessive 10.1 CENPJ CEP152
12 microcephaly 17, primary, autosomal recessive 10.0 CENPJ CEP152
13 microcephaly 6, primary, autosomal recessive 10.0 CENPJ CEP152
14 microcephaly 4, primary, autosomal recessive 10.0 CENPJ CEP152
15 microcephaly 12, primary, autosomal recessive 10.0 CENPJ CEP152
16 microcephaly 2, primary, autosomal recessive, with or without cortical malformations 10.0 CENPJ CEP152
17 meier-gorlin syndrome 1 10.0 ATR CEP152
18 microcephaly 5, primary, autosomal recessive 10.0 CENPJ CEP152
19 microcephaly 7, primary, autosomal recessive 10.0 CENPJ CEP152
20 primary autosomal recessive microcephaly 10.0 CENPJ CEP152
21 microcephaly 18, primary, autosomal dominant 10.0 CENPJ CEP152
22 congenital nervous system abnormality 9.9 CENPJ CEP152
23 primary microcephaly 9.9 CENPJ CEP152
24 ataxia-telangiectasia 9.8 ATR CHEK1

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



Diseases related to Seckel Syndrome 1

Symptoms & Phenotypes for Seckel Syndrome 1

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
pachygyria
mental retardation
arachnoidal cysts
large basal ganglia
more
Skeletal Feet:
pes planus
talipes
gap between first and second toes

Head And Neck Face:
micrognathia
facial asymmetry
sloping forehead

Head And Neck Eyes:
strabismus
blepharophimosis
downslanting palpebral fissures
relatively large eyes

Skeletal Limbs:
elbow flexion contracture
hypoplasia of proximal radius
radial head dislocation
hypoplasia of proximal fibula
aberrant patellae

Genitourinary External Genitalia Male:
hypospadias

Neurologic Behavioral Psychiatric Manifestations:
hyperactivity

Genitourinary External Genitalia Female:
clitoromegaly

Skeletal Hands:
abnormal finger flexion creases
fifth finger clinodactyly
transverse palmar creases
ivory epiphyses (phalanges)
cone-shaped epiphyses (phalanges)

Skeletal:
delayed bone age

Growth Height:
short stature, proportionate

Head And Neck Head:
microcephaly, severe
small anterior fontanel

Skeletal Spine:
scoliosis

Head And Neck Mouth:
cleft palate
high-arched palate

Hematology:
pancytopenia
increased sister chromatid exchange

Genitourinary Internal Genitalia Male:
cryptorchidism

Skeletal Pelvis:
hip dislocation

Head And Neck Teeth:
dental crowding
selective tooth agenesis
enamel hypoplasia
class ii malocclusion

Head And Neck Nose:
prominent nose
beaked nose

Chest Ribs Sternum Clavicles And Scapulae:
11 pairs of ribs

Skin Nails Hair Skin:
abnormal finger flexion creases
transverse palmar creases

Growth Other:
prenatal growth retardation
postnatal growth retardation (-7 s.d.)

Growth Weight:
average birth weight 1540g

Head And Neck Ears:
low-set, malformed ears
absence of earlobe


Clinical features from OMIM:

210600

Human phenotypes related to Seckel Syndrome 1:

32 (show all 48)
# Description HPO Frequency HPO Source Accession
1 low-set ears 32 HP:0000369
2 high palate 32 HP:0000218
3 intellectual disability 32 HP:0001249
4 seizures 32 HP:0001250
5 scoliosis 32 HP:0002650
6 dental malocclusion 32 HP:0000689
7 delayed skeletal maturation 32 HP:0002750
8 pes planus 32 HP:0001763
9 microcephaly 32 HP:0000252
10 cleft palate 32 HP:0000175
11 micrognathia 32 HP:0000347
12 pancytopenia 32 HP:0001876
13 strabismus 32 HP:0000486
14 cryptorchidism 32 HP:0000028
15 intrauterine growth retardation 32 HP:0001511
16 postnatal growth retardation 32 HP:0008897
17 elbow flexion contracture 32 HP:0002987
18 abnormality of the pinna 32 HP:0000377
19 hip dislocation 32 HP:0002827
20 hypospadias 32 HP:0000047
21 clinodactyly of the 5th finger 32 HP:0004209
22 dental crowding 32 HP:0000678
23 downslanted palpebral fissures 32 HP:0000494
24 sandal gap 32 HP:0001852
25 blepharophimosis 32 HP:0000581
26 convex nasal ridge 32 HP:0000444
27 facial asymmetry 32 HP:0000324
28 pachygyria 32 HP:0001302
29 sloping forehead 32 HP:0000340
30 talipes 32 HP:0001883
31 hyperactivity 32 HP:0000752
32 prominent nose 32 HP:0000448
33 single transverse palmar crease 32 HP:0000954
34 cerebellar vermis hypoplasia 32 HP:0001320
35 cone-shaped epiphyses of the phalanges of the hand 32 HP:0010230
36 11 pairs of ribs 32 HP:0000878
37 dislocated radial head 32 HP:0003083
38 hypoplasia of dental enamel 32 HP:0006297
39 selective tooth agenesis 32 HP:0001592
40 proportionate short stature 32 HP:0003508
41 clitoral hypertrophy 32 HP:0008665
42 abnormal finger flexion creases 32 HP:0006143
43 small anterior fontanelle 32 HP:0000237
44 hypoplasia of proximal radius 32 HP:0006434
45 hypoplasia of proximal fibula 32 HP:0006442
46 large basal ganglia 32 HP:0007048
47 ivory epiphyses 32 HP:0010583
48 abnormally large globe 32 HP:0001090

UMLS symptoms related to Seckel Syndrome 1:


seizures

GenomeRNAi Phenotypes related to Seckel Syndrome 1 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-3 9.46 ATR CHEK1 MNAT1 RBBP8
2 Decreased telomerase activity GR00156-A 9.37 ATR CHEK1
3 Decreased viability after gemcitabine stimulation GR00107-A-2 9.32 ATR CHEK1
4 Decreased viability with poly (ADPa89ribose)a89polymerasea891 (PARP) inhibitor GR00114-A 9.26 ATR CHEK1
5 Synthetic lethal with cisplatin GR00101-A-1 8.96 ATR CHEK1
6 Synthetic lethal with gemcitabine GR00101-A-2 8.8 CHEK1
7 Synthetic lethal with gemcitabine GR00225-A 8.8 ATR CHEK1

MGI Mouse Phenotypes related to Seckel Syndrome 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.1 ATR CENPJ CEP152 CHEK1 MNAT1 RBBP8

Drugs & Therapeutics for Seckel Syndrome 1

Search Clinical Trials , NIH Clinical Center for Seckel Syndrome 1

Genetic Tests for Seckel Syndrome 1

Genetic tests related to Seckel Syndrome 1:

# Genetic test Affiliating Genes
1 Seckel Syndrome 1 29 ATR

Anatomical Context for Seckel Syndrome 1

MalaCards organs/tissues related to Seckel Syndrome 1:

41
Bone, Eye

Publications for Seckel Syndrome 1

Articles related to Seckel Syndrome 1:

# Title Authors Year
1
Studies of microcephalic primordial dwarfism I: approach to a delineation of the Seckel syndrome. ( 7046443 )
1982

Variations for Seckel Syndrome 1

ClinVar genetic disease variations for Seckel Syndrome 1:

6 (show all 42)
# Gene Variation Type Significance SNP ID Assembly Location
1 ATR NM_001184.3(ATR): c.2022A> G (p.Gly674=) single nucleotide variant Pathogenic rs587776690 GRCh37 Chromosome 3, 142275281: 142275281
2 ATR NM_001184.3(ATR): c.2022A> G (p.Gly674=) single nucleotide variant Pathogenic rs587776690 GRCh38 Chromosome 3, 142556439: 142556439
3 ATR NM_001184.3(ATR): c.5635G> T (p.Asp1879Tyr) single nucleotide variant Pathogenic rs387907327 GRCh37 Chromosome 3, 142215958: 142215958
4 ATR NM_001184.3(ATR): c.5635G> T (p.Asp1879Tyr) single nucleotide variant Pathogenic rs387907327 GRCh38 Chromosome 3, 142497116: 142497116
5 ATR NM_001184.3(ATR): c.3477G> T (p.Met1159Ile) single nucleotide variant Pathogenic rs587777851 GRCh38 Chromosome 3, 142541008: 142541008
6 ATR NM_001184.3(ATR): c.3477G> T (p.Met1159Ile) single nucleotide variant Pathogenic rs587777851 GRCh37 Chromosome 3, 142259850: 142259850
7 ATR NM_001184.3(ATR): c.6897+464C> G single nucleotide variant Pathogenic rs587777852 GRCh38 Chromosome 3, 142465860: 142465860
8 ATR NM_001184.3(ATR): c.6897+464C> G single nucleotide variant Pathogenic rs587777852 GRCh37 Chromosome 3, 142184702: 142184702
9 ATR NM_001184.3(ATR): c.1350-3T> C single nucleotide variant Uncertain significance rs587783323 GRCh37 Chromosome 3, 142279299: 142279299
10 ATR NM_001184.3(ATR): c.1350-3T> C single nucleotide variant Uncertain significance rs587783323 GRCh38 Chromosome 3, 142560457: 142560457
11 ATR NM_001184.3(ATR): c.2290A> G (p.Lys764Glu) single nucleotide variant Conflicting interpretations of pathogenicity rs77208665 GRCh37 Chromosome 3, 142274770: 142274770
12 ATR NM_001184.3(ATR): c.2290A> G (p.Lys764Glu) single nucleotide variant Conflicting interpretations of pathogenicity rs77208665 GRCh38 Chromosome 3, 142555928: 142555928
13 ATR NM_001184.3(ATR): c.2688G> A (p.Leu896=) single nucleotide variant Uncertain significance rs117926957 GRCh37 Chromosome 3, 142272186: 142272186
14 ATR NM_001184.3(ATR): c.2688G> A (p.Leu896=) single nucleotide variant Uncertain significance rs117926957 GRCh38 Chromosome 3, 142553344: 142553344
15 ATR NM_001184.3(ATR): c.3424A> G (p.Ser1142Gly) single nucleotide variant Uncertain significance rs149008479 GRCh37 Chromosome 3, 142261533: 142261533
16 ATR NM_001184.3(ATR): c.3424A> G (p.Ser1142Gly) single nucleotide variant Uncertain significance rs149008479 GRCh38 Chromosome 3, 142542691: 142542691
17 ATR NM_001184.3(ATR): c.3799G> A (p.Val1267Ile) single nucleotide variant Uncertain significance rs377689383 GRCh37 Chromosome 3, 142254970: 142254970
18 ATR NM_001184.3(ATR): c.3799G> A (p.Val1267Ile) single nucleotide variant Uncertain significance rs377689383 GRCh38 Chromosome 3, 142536128: 142536128
19 ATR NM_001184.3(ATR): c.4306A> G (p.Asn1436Asp) single nucleotide variant Uncertain significance rs587783328 GRCh37 Chromosome 3, 142238587: 142238587
20 ATR NM_001184.3(ATR): c.4306A> G (p.Asn1436Asp) single nucleotide variant Uncertain significance rs587783328 GRCh38 Chromosome 3, 142519745: 142519745
21 ATR NM_001184.3(ATR): c.4351C> T (p.Arg1451Trp) single nucleotide variant Uncertain significance rs148064542 GRCh37 Chromosome 3, 142238542: 142238542
22 ATR NM_001184.3(ATR): c.4351C> T (p.Arg1451Trp) single nucleotide variant Uncertain significance rs148064542 GRCh38 Chromosome 3, 142519700: 142519700
23 ATR NM_001184.3(ATR): c.4641+15C> T single nucleotide variant Uncertain significance rs200619976 GRCh37 Chromosome 3, 142232328: 142232328
24 ATR NM_001184.3(ATR): c.4641+15C> T single nucleotide variant Uncertain significance rs200619976 GRCh38 Chromosome 3, 142513486: 142513486
25 ATR NM_001184.3(ATR): c.5732A> G (p.Asn1911Ser) single nucleotide variant Uncertain significance rs587783334 GRCh37 Chromosome 3, 142215861: 142215861
26 ATR NM_001184.3(ATR): c.5732A> G (p.Asn1911Ser) single nucleotide variant Uncertain significance rs587783334 GRCh38 Chromosome 3, 142497019: 142497019
27 ATR NM_001184.3(ATR): c.5739-14G> T single nucleotide variant Uncertain significance rs587783335 GRCh37 Chromosome 3, 142215376: 142215376
28 ATR NM_001184.3(ATR): c.5739-14G> T single nucleotide variant Uncertain significance rs587783335 GRCh38 Chromosome 3, 142496534: 142496534
29 ATR NM_001184.3(ATR): c.6961T> C (p.Phe2321Leu) single nucleotide variant Uncertain significance rs587783338 GRCh37 Chromosome 3, 142184019: 142184019
30 ATR NM_001184.3(ATR): c.6961T> C (p.Phe2321Leu) single nucleotide variant Uncertain significance rs587783338 GRCh38 Chromosome 3, 142465177: 142465177
31 ATR NM_001184.3(ATR): c.7041+4G> C single nucleotide variant Uncertain significance rs113544835 GRCh37 Chromosome 3, 142183935: 142183935
32 ATR NM_001184.3(ATR): c.7041+4G> C single nucleotide variant Uncertain significance rs113544835 GRCh38 Chromosome 3, 142465093: 142465093
33 ATR NM_001184.3(ATR): c.7725G> A (p.Ala2575=) single nucleotide variant Uncertain significance rs587783340 GRCh37 Chromosome 3, 142172006: 142172006
34 ATR NM_001184.3(ATR): c.7725G> A (p.Ala2575=) single nucleotide variant Uncertain significance rs587783340 GRCh38 Chromosome 3, 142453164: 142453164
35 ATR NM_001184.3(ATR): c.4641+1G> T single nucleotide variant Pathogenic rs797045403 GRCh37 Chromosome 3, 142232342: 142232342
36 ATR NM_001184.3(ATR): c.4641+1G> T single nucleotide variant Pathogenic rs797045403 GRCh38 Chromosome 3, 142513500: 142513500
37 ATR NM_001184.3(ATR): c.5196+1G> A single nucleotide variant Likely pathogenic GRCh38 Chromosome 3, 142505138: 142505138
38 ATR NM_001184.3(ATR): c.5196+1G> A single nucleotide variant Likely pathogenic GRCh37 Chromosome 3, 142223980: 142223980
39 ATR NM_001184.3(ATR): c.4995G> T (p.Lys1665Asn) single nucleotide variant Likely pathogenic GRCh38 Chromosome 3, 142507967: 142507967
40 ATR NM_001184.3(ATR): c.4995G> T (p.Lys1665Asn) single nucleotide variant Likely pathogenic GRCh37 Chromosome 3, 142226809: 142226809
41 ATR NM_001184.3(ATR): c.151+4A> G single nucleotide variant Likely pathogenic rs1481733213 GRCh38 Chromosome 3, 142568059: 142568059
42 ATR NM_001184.3(ATR): c.151+4A> G single nucleotide variant Likely pathogenic rs1481733213 GRCh37 Chromosome 3, 142286901: 142286901

Expression for Seckel Syndrome 1

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

Pathways for Seckel Syndrome 1

Pathways related to Seckel Syndrome 1 according to GeneCards Suite gene sharing:

(show all 16)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.28 APEH ATR CENPJ CHEK1 MNAT1 RBBP8
2
Show member pathways
12.84 ATR CHEK1 MNAT1 RBBP8
3
Show member pathways
12.59 ATR CENPJ CEP152 CHEK1 MNAT1 RBBP8
4
Show member pathways
12.37 ATR CENPJ CHEK1 MNAT1 RBBP8
5
Show member pathways
12.29 ATR CHEK1 RBBP8
6 12.12 ATR CHEK1 RBBP8
7
Show member pathways
11.88 ATR CHEK1 RBBP8
8
Show member pathways
11.35 ATR CHEK1 RBBP8
9 11.33 ATR CHEK1
10 11.19 ATR CHEK1
11
Show member pathways
11.16 ATR CHEK1
12 11.14 ATR CHEK1
13 10.92 ATR RBBP8
14 10.79 ATR CHEK1
15 10.47 ATR CHEK1
16 10.46 ATR CHEK1 RBBP8

GO Terms for Seckel Syndrome 1

Cellular components related to Seckel Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 centrosome GO:0005813 9.33 CENPJ CEP152 CHEK1
2 microtubule organizing center GO:0005815 9.13 CENPJ CEP152 CHEK1
3 nucleoplasm GO:0005654 9.1 ATR CENPJ CEP152 CHEK1 MNAT1 RBBP8

Biological processes related to Seckel Syndrome 1 according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 9.67 ATR CHEK1 RBBP8
2 ciliary basal body-plasma membrane docking GO:0097711 9.52 CENPJ CEP152
3 G1/S transition of mitotic cell cycle GO:0000082 9.51 MNAT1 RBBP8
4 DNA replication GO:0006260 9.5 ATR CHEK1 RBBP8
5 regulation of G2/M transition of mitotic cell cycle GO:0010389 9.48 CENPJ CEP152
6 nucleotide-excision repair GO:0006289 9.46 MNAT1 RBBP8
7 negative regulation of G0 to G1 transition GO:0070317 9.43 CHEK1 RBBP8
8 DNA damage checkpoint GO:0000077 9.4 ATR CHEK1
9 centriole replication GO:0007099 9.37 CENPJ CEP152
10 centrosome duplication GO:0051298 9.26 CENPJ CEP152
11 replicative senescence GO:0090399 9.16 ATR CHEK1
12 G2/M transition of mitotic cell cycle GO:0000086 9.13 CENPJ CEP152 CHEK1
13 DNA repair GO:0006281 8.92 ATR CHEK1 MNAT1 RBBP8

Sources for Seckel Syndrome 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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