SCKL2
MCID: SCK015
MIFTS: 40

Seckel Syndrome 2 (SCKL2)

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

Aliases & Classifications for Seckel Syndrome 2

MalaCards integrated aliases for Seckel Syndrome 2:

Name: Seckel Syndrome 2 57 12 72 29 13 6 15 70
Microcephalic Primordial Dwarfism 2 57 12 72
Seckel-Type Dwarfism 2 57 12 72
Sckl2 57 12 72
Seckel Syndrome, Type 2 39
Bird-Headed Dwarfism 2 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive


HPO:

31
seckel syndrome 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Seckel Syndrome 2

OMIM® : 57 Seckel syndrome is a rare autosomal recessive disorder characterized by growth retardation, microcephaly with mental retardation, and a characteristic facial appearance (Borglum et al., 2001). For a general phenotypic description and a discussion of genetic heterogeneity of Seckel syndrome, see SCKL1 (210600). (606744) (Updated 20-May-2021)

MalaCards based summary : Seckel Syndrome 2, also known as microcephalic primordial dwarfism 2, is related to dwarfism and microcephaly 14, primary, autosomal recessive. An important gene associated with Seckel Syndrome 2 is RBBP8 (RB Binding Protein 8, Endonuclease), and among its related pathways/superpathways are Regulation of PLK1 Activity at G2/M Transition and Cell Cycle, Mitotic. Affiliated tissues include eye, cerebellum and heart, and related phenotypes are ectopic kidney and high pitched voice

Disease Ontology : 12 A Seckel syndrome that has material basis in homozygous mutation in the RBBP8 gene on chromosome 18q11.

UniProtKB/Swiss-Prot : 72 Seckel syndrome 2: 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.

Related Diseases for Seckel Syndrome 2

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 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 38)
# Related Disease Score Top Affiliating Genes
1 dwarfism 30.6 PCNT DNA2
2 microcephaly 14, primary, autosomal recessive 10.1 CEP152 CENPJ
3 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 6 10.1 RBBP8 DNA2
4 microcephaly 10, primary, autosomal recessive 10.1 CEP152 CENPJ
5 seckel syndrome 8 10.0 RBBP8 DNA2 CEP152
6 mosaic variegated aneuploidy syndrome 10.0 PCNT CNTLN CEP152
7 microcephaly 11, primary, autosomal recessive 9.9 MCPH1 CEP152 CENPJ
8 microcephaly 13, primary, autosomal recessive 9.9 MCPH1 CEP152
9 microcephaly 18, primary, autosomal dominant 9.9 MCPH1 CEP152 CENPJ
10 microcephaly 1, primary, autosomal recessive 9.9 MCPH1 CEP152 CENPJ
11 band heterotopia 9.7 MCPH1 CENPJ CDK5RAP2
12 periventricular nodular heterotopia 9.7 MCPH1 CENPJ CDK5RAP2
13 meckel syndrome, type 1 9.7 PCNT CNTLN CEP152
14 miller-dieker lissencephaly syndrome 9.7 RFC2 MCPH1 CDK5RAP2
15 microcephaly 8, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
16 microcephaly 12, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
17 microcephaly 9, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
18 microcephaly 17, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
19 microcephaly 3, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
20 microcephaly 7, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
21 microcephaly 4, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
22 microcephaly 5, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
23 seckel syndrome 5 9.7 RBBP8 PCNT MCPH1 CEP152 CENPJ
24 primary microcephaly 9.6 MCPH1 CEP152 CENPJ CDK5RAP2
25 autosomal recessive non-syndromic intellectual disability 9.6 MCPH1 CEP152 CDK5RAP2
26 joubert syndrome 1 9.5 PCNT CNTLN CEP152 CENPJ CDK5RAP2
27 microcephaly 2, primary, autosomal recessive, with or without cortical malformations 9.5 MCPH1 CNTLN CEP152 CENPJ CDK5RAP2
28 microcephaly 6, primary, autosomal recessive 9.5 MCPH1 CNTLN CEP152 CENPJ CDK5RAP2
29 isolated growth hormone deficiency 9.4 PCNT DNA2 CNTLN CEP152 CENPJ CDK5RAP2
30 microcephalic osteodysplastic primordial dwarfism, type ii 9.3 PCNT MCPH1 CNTLN CEP152 CENPJ CDK5RAP2
31 congenital nervous system abnormality 9.3 PCNT MCPH1 CNTLN CEP152 CENPJ CDK5RAP2
32 physical disorder 9.3 PCNT MCPH1 CNTLN CEP152 CENPJ CDK5RAP2
33 primary autosomal recessive microcephaly 9.2 RBBP8 PCNT MCPH1 CNTLN CEP152 CENPJ
34 microcephaly 9.2 RBBP8 PCNT MCPH1 DNA2 CEP152 CENPJ
35 isolated growth hormone deficiency, type ia 9.0 RBBP8 PCNT MCPH1 DNA2 CNTLN CEP152
36 seckel syndrome 4 9.0 RFC2 RBBP8 PCNT MCPH1 CNTLN CEP152
37 seckel syndrome 1 8.7 RFC2 RBBP8 PCNT MNAT1 MCPH1 CNTLN
38 seckel syndrome 8.7 RFC2 RBBP8 PCNT MCPH1 DNA2 CNTLN

Graphical network of the top 20 diseases related to Seckel Syndrome 2:



Diseases related to Seckel Syndrome 2

Symptoms & Phenotypes for Seckel Syndrome 2

Human phenotypes related to Seckel Syndrome 2:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 ectopic kidney 31 occasional (7.5%) HP:0000086
2 high pitched voice 31 very rare (1%) HP:0001620
3 microcephaly 31 HP:0000252
4 short stature 31 HP:0004322
5 microdontia 31 HP:0000691
6 growth delay 31 HP:0001510
7 micrognathia 31 HP:0000347
8 clinodactyly of the 5th finger 31 HP:0004209
9 microphthalmia 31 HP:0000568
10 hypospadias 31 HP:0000047
11 cerebellar hypoplasia 31 HP:0001321
12 mild global developmental delay 31 HP:0011342
13 prominent nose 31 HP:0000448
14 small for gestational age 31 HP:0001518
15 microglossia 31 HP:0000171
16 narrow forehead 31 HP:0000341
17 heart murmur 31 HP:0030148
18 few cafe-au-lait spots 31 HP:0007429

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Head:
microcephaly
micrognathia

Head And Neck Eyes:
microphthalmia

Head And Neck Nose:
prominent nose

Cardiovascular Heart:
heart murmur

Voice:
high-pitched voice

Skin Nails Hair Skin:
cafe au lait spots

Growth Height:
proportionate short stature at birth

Genitourinary External Genitalia Male:
mild hypospadias

Skeletal Hands:
swelling over proximal part of middle phalanx of second, third, and fourth fingers
clinodactyly of fifth finger
absence of epiphyseal ossification centers of distal and middle phalangeal bones of fifth finger
synostosis of distal interphalangeal joint of fifth finger

Skeletal Skull:
microcephaly
short anterior cranial base
short maxillary length

Neurologic Central Nervous System:
mild global developmental delay
mild cerebellar hypoplasia
bilateral calcification of basal ganglia and cerebellum

Head And Neck Mouth:
microglossia

Head And Neck Teeth:
small teeth

Growth Weight:
low birth weight
underweight

Skeletal Limbs:
slender extremities

Growth Other:
persistent growth deficiency

Genitourinary Kidneys:
ectopic kidneys (rare)

Clinical features from OMIM®:

606744 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Seckel Syndrome 2 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.17 MCPH1
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.17 MCPH1 MNAT1
3 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-3 9.17 DNA2 MCPH1 RBBP8 RFC2

Drugs & Therapeutics for Seckel Syndrome 2

Search Clinical Trials , NIH Clinical Center for Seckel Syndrome 2

Genetic Tests for Seckel Syndrome 2

Genetic tests related to Seckel Syndrome 2:

# Genetic test Affiliating Genes
1 Seckel Syndrome 2 29 RBBP8

Anatomical Context for Seckel Syndrome 2

MalaCards organs/tissues related to Seckel Syndrome 2:

40
Eye, Cerebellum, Heart, Kidney

Publications for Seckel Syndrome 2

Articles related to Seckel Syndrome 2:

# Title Authors PMID Year
1
Genomic analysis of primordial dwarfism reveals novel disease genes. 6 57
24389050 2014
2
A new locus for Seckel syndrome on chromosome 18p11.31-q11.2. 57 6
11781686 2001
3
CtIP Mutations Cause Seckel and Jawad Syndromes. 61 57
21998596 2011
4
A complex microcephaly syndrome in a Pakistani family associated with a novel missense mutation in RBBP8 and a heterozygous deletion in NRXN1. 61
24440292 2014
5
Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY 61
20301772 2009
6
Is the novel SCKL3 at 14q23 the predominant Seckel locus? 61
14571270 2003

Variations for Seckel Syndrome 2

ClinVar genetic disease variations for Seckel Syndrome 2:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RBBP8 NM_002894.3(RBBP8):c.2287+53T>G SNV Pathogenic 30408 rs587776883 GRCh37: 18:20581745-20581745
GRCh38: 18:23001782-23001782
2 RBBP8 NM_002894.3(RBBP8):c.298C>T (p.Arg100Trp) SNV Pathogenic 127245 rs373804633 GRCh37: 18:20548818-20548818
GRCh38: 18:22968855-22968855
3 RBBP8 NM_002894.3(RBBP8):c.604+1G>T SNV Pathogenic 130101 rs587780432 GRCh37: 18:20562357-20562357
GRCh38: 18:22982394-22982394

UniProtKB/Swiss-Prot genetic disease variations for Seckel Syndrome 2:

72
# Symbol AA change Variation ID SNP ID
1 RBBP8 p.Arg100Trp VAR_075824 rs373804633

Expression for Seckel Syndrome 2

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

Pathways for Seckel Syndrome 2

GO Terms for Seckel Syndrome 2

Cellular components related to Seckel Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleoplasm GO:0005654 9.97 RFC2 RBBP8 MNAT1 MCPH1 DNA2 CNTLN
2 cytoskeleton GO:0005856 9.73 PCNT MCPH1 CNTLN CEP152 CENPJ CDK5RAP2
3 centrosome GO:0005813 9.55 PCNT CNTLN CEP152 CENPJ CDK5RAP2
4 microtubule organizing center GO:0005815 9.35 PCNT MCPH1 CEP152 CENPJ CDK5RAP2
5 pericentriolar material GO:0000242 9.32 CEP152 CDK5RAP2
6 centriole GO:0005814 8.92 PCNT CNTLN CEP152 CENPJ

Biological processes related to Seckel Syndrome 2 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 DNA repair GO:0006281 9.77 RFC2 RBBP8 MNAT1 EXD2 DNA2
2 DNA replication GO:0006260 9.63 RFC2 RBBP8 DNA2
3 regulation of signal transduction by p53 class mediator GO:1901796 9.61 RFC2 RBBP8 DNA2
4 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.58 RBBP8 EXD2 DNA2
5 ciliary basal body-plasma membrane docking GO:0097711 9.56 PCNT CEP152 CENPJ CDK5RAP2
6 centriole replication GO:0007099 9.5 CEP152 CENPJ CDK5RAP2
7 establishment of mitotic spindle orientation GO:0000132 9.49 MCPH1 CDK5RAP2
8 telomere maintenance via semi-conservative replication GO:0032201 9.48 RFC2 DNA2
9 regulation of G2/M transition of mitotic cell cycle GO:0010389 9.46 PCNT CEP152 CENPJ CDK5RAP2
10 DNA double-strand break processing GO:0000729 9.13 RBBP8 EXD2 DNA2
11 G2/M transition of mitotic cell cycle GO:0000086 9.02 PCNT MNAT1 CEP152 CENPJ CDK5RAP2

Molecular functions related to Seckel Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein kinase binding GO:0019901 9.46 CNTLN CEP152 CENPJ CDK5RAP2
2 gamma-tubulin binding GO:0043015 9.26 CENPJ CDK5RAP2
3 nuclease activity GO:0004518 9.13 RBBP8 EXD2 DNA2
4 single-stranded DNA-dependent ATP-dependent DNA helicase activity GO:0017116 8.62 RFC2 DNA2

Sources for Seckel 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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