SCKL2
MCID: SCK015
MIFTS: 40

Seckel Syndrome 2 (SCKL2)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Smell/Taste diseases
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Aliases & Classifications for Seckel Syndrome 2

MalaCards integrated aliases for Seckel Syndrome 2:

Name: Seckel Syndrome 2 57 11 73 28 12 5 14 71
Microcephalic Primordial Dwarfism 2 57 11 73
Seckel-Type Dwarfism 2 57 11 73
Sckl2 57 11 73
Seckel Syndrome, Type 2 38
Bird-Headed Dwarfism 2 73

Characteristics:


Inheritance:

Autosomal recessive 57

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 24-Oct-2022)

MalaCards based summary: Seckel Syndrome 2, also known as microcephalic primordial dwarfism 2, is related to seckel syndrome and seckel syndrome 1. An important gene associated with Seckel Syndrome 2 is RBBP8 (RB Binding Protein 8, Endonuclease), and among its related pathways/superpathways are Loss of Nlp from mitotic centrosomes and Homology Directed Repair. Affiliated tissues include heart, cerebellum and kidney, and related phenotypes are ectopic kidney and high pitched voice

UniProtKB/Swiss-Prot: 73 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 intellectual disability.

Disease Ontology: 11 A Seckel syndrome that has material basis in homozygous mutation in the RBBP8 gene on chromosome 18q11.

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 43)
# Related Disease Score Top Affiliating Genes
1 seckel syndrome 28.2 RFC2 RBBP8 PCNT MCPH1 H2AC18 DNA2
2 seckel syndrome 1 10.2
3 microcephaly 16, primary, autosomal recessive 10.2 CEP152 CENPJ
4 microcephaly 6, primary, autosomal recessive 10.2 CEP152 CENPJ
5 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 6 10.1 RBBP8 DNA2
6 lissencephaly 2 10.1 CEP152 CENPJ
7 fibrochondrogenesis 2 10.1 RBBP8 COL11A2
8 microcephaly, autosomal dominant 10.1 CEP152 CDK5RAP2
9 sporadic breast cancer 10.1 RBBP8 H2AC18
10 seckel syndrome 8 10.0 RBBP8 DNA2 CEP152
11 rothmund-thomson syndrome, type 2 10.0 H2AC18 DNA2
12 mosaic variegated aneuploidy syndrome 10.0 PCNT CNTLN CEP152
13 microlissencephaly 10.0 CEP152 CENPJ CDK5RAP2
14 microcephaly 1, primary, autosomal recessive 9.9 MCPH1 CENPJ
15 trichothiodystrophy 9.9 MNAT1 H2AC18 DNA2
16 hereditary breast ovarian cancer syndrome 9.9 RBBP8 H2AC18 DNA2
17 microcephaly 11, primary, autosomal recessive 9.9 MCPH1 H2AC18 CENPJ
18 seckel syndrome 5 9.9 MCPH1 CEP152 CENPJ
19 microcephaly 18, primary, autosomal dominant 9.9 MCPH1 CEP152 CENPJ
20 band heterotopia 9.8 MCPH1 CENPJ CDK5RAP2
21 fanconi anemia, complementation group a 9.8 RBBP8 H2AC18 DNA2 CNTLN
22 periventricular nodular heterotopia 9.7 MCPH1 CENPJ CDK5RAP2
23 osteochondrodysplasia 9.7 PCNT H2AC18 COL11A2
24 meckel syndrome, type 1 9.7 PCNT CNTLN CEP152
25 microcephaly 14, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
26 microcephaly 17, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
27 microcephaly 12, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
28 microcephaly 10, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
29 microcephaly 9, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
30 microcephaly 13, primary, autosomal recessive 9.7 MCPH1 CEP152 CENPJ CDK5RAP2
31 meier-gorlin syndrome 1 9.6 RBBP8 PCNT H2AC18 CNTLN CEP152 CENPJ
32 joubert syndrome 1 9.6 PCNT CNTLN CEP152 CENPJ CDK5RAP2
33 miller-dieker lissencephaly syndrome 9.5 RFC2 MCPH1 CENPJ CDK5RAP2
34 isolated growth hormone deficiency 9.5 PCNT H2AC18 CNTLN CEP152 CENPJ CDK5RAP2
35 physical disorder 9.5 MCPH1 H2AC18 CEP152 CENPJ CDK5RAP2
36 seckel syndrome 4 9.5 PCNT MCPH1 CNTLN CENPJ CDK5RAP2
37 microcephaly 5, primary, autosomal recessive 9.4 PCNT MCPH1 H2AC18 CEP152 CENPJ CDK5RAP2
38 microcephalic osteodysplastic primordial dwarfism, type ii 9.3 PCNT MCPH1 CNTLN CEP152 CENPJ CDK5RAP2
39 primary microcephaly 9.2 PCNT MCPH1 H2AC18 CNTLN CEP152 CENPJ
40 primary autosomal recessive microcephaly 9.1 RBBP8 PCNT MCPH1 H2AC18 CNTLN CEP152
41 congenital nervous system abnormality 9.1 RBBP8 PCNT MCPH1 H2AC18 CNTLN CEP152
42 isolated growth hormone deficiency, type ia 9.0 PCNT MCPH1 H2AC18 DNA2 CNTLN CEP152
43 microcephaly 8.9 RBBP8 PCNT MCPH1 H2AC18 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:

30 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ectopic kidney 30 Occasional (7.5%) HP:0000086
2 high pitched voice 30 Very rare (1%) HP:0001620
3 microcephaly 30 HP:0000252
4 short stature 30 HP:0004322
5 microdontia 30 HP:0000691
6 growth delay 30 HP:0001510
7 micrognathia 30 HP:0000347
8 clinodactyly of the 5th finger 30 HP:0004209
9 microphthalmia 30 HP:0000568
10 hypospadias 30 HP:0000047
11 cerebellar hypoplasia 30 HP:0001321
12 mild global developmental delay 30 HP:0011342
13 prominent nose 30 HP:0000448
14 small for gestational age 30 HP:0001518
15 microglossia 30 HP:0000171
16 narrow forehead 30 HP:0000341
17 heart murmur 30 HP:0030148
18 few cafe-au-lait spots 30 HP:0007429

Symptoms via clinical synopsis from OMIM®:

57 (Updated 24-Oct-2022)
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 24-Oct-2022)

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

25
# 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 28 RBBP8

Anatomical Context for Seckel Syndrome 2

Organs/tissues related to Seckel Syndrome 2:

MalaCards : Heart, Cerebellum, 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. 57 5
24389050 2014
2
A new locus for Seckel syndrome on chromosome 18p11.31-q11.2. 57 5
11781686 2001
3
CtIP Mutations Cause Seckel and Jawad Syndromes. 62 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. 62
24440292 2014
5
Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY 62
20301772 2009
6
Is the novel SCKL3 at 14q23 the predominant Seckel locus? 62
14571270 2003
7
Seckel's syndrome or bird-headed dwarfism (2 cases reports). 62
751929 1978

Variations for Seckel Syndrome 2

ClinVar genetic disease variations for Seckel Syndrome 2:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RBBP8 NM_002894.3(RBBP8):c.298C>T (p.Arg100Trp) SNV Pathogenic
127245 rs373804633 GRCh37: 18:20548818-20548818
GRCh38: 18:22968855-22968855
2 RBBP8 NM_002894.3(RBBP8):c.604+1G>T SNV Pathogenic
130101 rs587780432 GRCh37: 18:20562357-20562357
GRCh38: 18:22982394-22982394
3 RBBP8 NM_002894.3(RBBP8):c.2287+53T>G SNV Pathogenic
30408 rs587776883 GRCh37: 18:20581745-20581745
GRCh38: 18:23001782-23001782
4 RBBP8 NM_002894.3(RBBP8):c.2048T>G (p.Leu683Ter) SNV Likely Pathogenic
1683598 GRCh37: 18:20577602-20577602
GRCh38: 18:22997639-22997639
5 RBBP8 NM_002894.3(RBBP8):c.139C>T (p.Gln47Ter) SNV Likely Pathogenic
392730 rs762396810 GRCh37: 18:20526436-20526436
GRCh38: 18:22946473-22946473
6 RBBP8 NM_002894.3(RBBP8):c.2115G>A (p.Lys705=) SNV Benign
130107 rs17852769 GRCh37: 18:20577669-20577669
GRCh38: 18:22997706-22997706
7 RBBP8 NM_002894.3(RBBP8):c.428+37T>C SNV Benign
673936 rs2336916 GRCh37: 18:20555219-20555219
GRCh38: 18:22975256-22975256
8 RBBP8 NM_002894.3(RBBP8):c.605-48TCA[2] MICROSAT Benign
1263878 GRCh37: 18:20564801-20564803
GRCh38: 18:22984838-22984840

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

73
# 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

Pathways related to Seckel Syndrome 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.75 PCNT MNAT1 CEP152 CENPJ CDK5RAP2
2
Show member pathways
12.55 RFC2 RBBP8 MNAT1 H2AC18 DNA2
3
Show member pathways
12.55 RFC2 RBBP8 PCNT MNAT1 MCPH1 H2AC18
4
Show member pathways
12.25 PCNT CEP152 CENPJ CDK5RAP2
5
Show member pathways
12.16 RFC2 RBBP8 MNAT1 DNA2 CENPJ
6
Show member pathways
11.95 RFC2 H2AC18 DNA2

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 centrosome GO:0005813 9.96 PCNT CNTLN CEP152 CENPJ CDK5RAP2
2 cytoskeleton GO:0005856 9.87 PCNT MCPH1 CNTLN CEP152 CENPJ CDK5RAP2
3 pericentriolar material GO:0000242 9.67 CEP152 CDK5RAP2
4 centriole GO:0005814 9.56 PCNT CNTLN CEP152 CENPJ
5 procentriole replication complex GO:0120099 9.46 CEP152 CENPJ
6 microtubule organizing center GO:0005815 9.1 PCNT MCPH1 CEP152 CENPJ CDK5RAP2

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

# Name GO ID Score Top Affiliating Genes
1 DNA repair GO:0006281 9.7 RFC2 RBBP8 MNAT1 DNA2
2 centrosome duplication GO:0051298 9.13 CEP152 CENPJ
3 centriole replication GO:0007099 9.1 CEP152 CENPJ CDK5RAP2

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

# Name GO ID Score Top Affiliating Genes
1 single-stranded DNA helicase activity GO:0017116 8.92 RFC2 DNA2

Sources for Seckel Syndrome 2

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 24-Oct-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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