Seckel Syndrome malady

NIH Rare Diseases: Seckel syndrome is a genetic disorder characterized by growth retardation, microcephaly with mental retardation, and unique facial features such as large eyes, beak-like nose, narrow face, and receding lower jaw. Blood abnormalities with chromosome breakage may be present in less than 25% of individuals who have Seckel syndrome. The signs and symptoms of Seckel syndrome may be similar to those of another condition called microcephalic osteodysplastic primordial dwarfism type II (MOPD II); however, MOPD II is associated with abnormalities of the bones, which can be identified by performing X-rays during the first years of life.Seckel syndrome is inherited in an autosomal recessive fashion. The condition may be called Seckel syndrome type 1 when it is caused by a mutation in the SCKL1 gene, Seckel syndrome type 2 when caused by a mutation in the SCKL2 gene, and Seckel syndrome type 3 when caused by a mutation in the SCKL3 gene.³⁰

MalaCards: Seckel Syndrome, also known as microcephalic primordial dwarfism, is related to dwarfism and ataxia telangiectasia. An important gene associated with Seckel Syndrome is ATR (ataxia telangiectasia and Rad3 related), and among its related pathways are Loss of Nlp from mitotic centrosomes and G2/M DNA damage checkpoint. The compounds iplex and methylmethanesulfonate have been mentioned in the context of this disorder. Affiliated tissues include pituitary, and related mouse phenotypes are craniofacial and embryogenesis.

Wikipedia: The Seckel syndrome or microcephalic primordial dwarfism (also known as bird-headed dwarfism, Harper\'s...⁴⁴ more...

Aliases & Descriptions:

seckel syndrome 6 7 30 16 8 32 43 microcephalic primordial dwarfism 6 16 nanocephalic dwarfism 30 16 bird-headed dwarfism 6 30 hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration 43

virchow-seckel dwarfism 6 pituitary dwarfism i 43 seckel-type dwarfism 30 harper's syndrome 6 sckl 30

Disease types for seckel syndrome family:

seckel syndrome 1	seckel syndrome 2
seckel syndrome 4	seckel syndrome 5
seckel syndrome 3

Diseases related to seckel syndrome by text searches and GeneDecks gene sharing:

(show top 50)    (show all 70)

id	Related Disease	Score	Top Affiliating Genes
1	dwarfism	27.6	IGFBP3, CEP152, PCNT, IGF1, CENPJ
2	ataxia telangiectasia	25.5	ATM, ATR, CHEK1, LIG4, IGF1R, MCPH1
3	fanconi's anemia	25.1	CHEK1, FANCA, LIG4, H2AFX, CNTLN, ATR
4	ataxia	24.9	IGF1R, PCNT, RBBP8, H2AFX, MDC1, ATM
5	anemia	23.8	ATR, IGF1, LIG4, FANCA, IGF1R, IGFBP3
6	dna ligase iv deficiency	13.3	ATR, LIG4
7	primary autosomal recessive microcephaly	13.2	ASPM, MCPH1, CENPJ
8	diffuse idiopathic skeletal hyperostosis	12.7	IGF1, IGFBP3
9	idiopathic juvenile osteoporosis	12.7	IGFBP3, IGF1
10	bloom syndrome	12.6	ATR, ATM, FANCA, H2AFX
11	ring chromosome 15	12.5	IGF1, IGF1R
12	breast cancer susceptibility	12.5	ATM, H2AFX, FANCA, ATR, LIG4
13	osteogenesis imperfecta	12.5	DSPP, IGFBP3, IGF1
14	female breast cancer	12.3	IGF1, IGFBP3, ATM
15	intrauterine and postnatal growth retardation	12.3	IGF1, IGF1R
16	donohue syndrome	12.3	IGF1, IGF1R
17	insulin-like growth factor 1 resistance to	12.2	IGF1R, IGFBP3, IGF1
18	rabson-mendenhall syndrome	12.2	IGFBP3, IGF1, IGF1R
19	growth disorders	12.1	IGF1, IGF1R, IGFBP3
20	polycystic ovary syndrome	12.1	IGF1, IGFBP3, IGF1R
21	testicular cancer	12.1	IGFBP3, IGF1, H2AFX, ATM
22	mental retardation syndrome	12.1	MCPH1, ASPM, ATM, ATR
23	silver-russell syndrome	12.1	IGF1R, IGF1, IGFBP3
24	hemangiopericytoma	12.1	IGF1, IGF1R, IGFBP3
25	werner syndrome	12.0	ATR, ATM, IGFBP3, IGF1, H2AFX
26	hereditary pancreatitis	12.0	FANCA, ATM, ATR, CHEK1, RBBP8, MCPH1
27	breast-ovarian cancer	11.8	IGF1R, FANCA, ATM, ATR, CHEK1
28	turner syndrome	11.8	IGF1, IGF1R, DSPP, IGFBP3
29	mantle cell lymphoma	11.7	CHEK1, ATM, H2AFX, IGF1R, PCNT
30	hereditary breast ovarian cancer	11.7	IGF1R, FANCA, ATM, IGF1
31	malignant glioma	11.4	ASPM, MCPH1, IGF1, H2AFX, IGF1R
32	growth retardation with deafness and mental retardation due to igf1 deficiency	11.4	LIG4, IGF1, ATM, IGF1R, IGFBP3, ATR
33	nijmegen breakage syndrome	11.3	H2AFX, MDC1, ATM, ATR, IGF1R, LIG4
34	short stature	11.3	IGF1, IGFBP3, DSPP, IGF1R
35	polyposis	11.2	H2AFX, IGF1, IGF1R, ATM, CHEK1, PCNT
36	sporadic breast cancer	11.1	CHEK1, H2AFX, IGF1R, FANCA, ATM, RBBP8
37	oral cancer	10.9	CHEK1, ATM, IGF1, DSPP, IGFBP3, IGF1R
38	lung carcinoma	10.9	DSPP, IGFBP3, IGF1R, ATM, CHEK1, LIG4
39	myeloid leukemia	10.7	ATM, CHEK1, DNM3, MCPH1, FANCA, IGFBP3
40	multiple myeloma	10.7	IGF1, LIG4, IGFBP3, IGF1R, ATM, CHEK1
41	lung cancer susceptibility	10.7	ATR, IGFBP3, LIG4, CHEK1, IGF1, IGF1R
42	harp syndrome	10.6
43	pulmonary disease	10.6	FANCA, ATM, IGF1R, IGFBP3, CHEK1, IGF1
44	breast carcinoma	10.5	IGFBP3, RBBP8, PCNT, H2AFX, IGF1R, ATM
45	epithelial ovarian cancer	10.5	IGFBP3, CHEK1, RBBP8, LIG4, ATR, ATM
46	myeloma	10.5	ATM, LIG4, H2AFX, IGF1, IGFBP3, CHEK1
47	microcephaly	10.4	CENPL, ATM, PCNT, ASPM, MCPH1, ATR
48	glioblastoma	10.3	IGF1, IGF1R, IGFBP3, H2AFX, LIG4, ASPM
49	osteosarcoma	10.3	CHEK1, IGF1R, ATM, IGFBP3, IGF1, H2AFX
50	esophagitis	10.2	IGF1R, FANCA, MDC1, ATM, ATR, CHEK1

Approved drugs:

Drug clinical trials:

Genetic tests related to seckel syndrome:

id	Genetic test	Affiliating Genes
1	Seckel Syndrome clinical/research	ATR, CENPJ, CEP152, LAP, RBBP8, SCKL2

MalaCards organs/tissues related to seckel syndrome:

²²

MGI Mouse Phenotypes related to seckel syndrome:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	craniofacial phenotype	MP:0005382	8.0	DSPP, IGF1R, FANCA, MCPH1, ASPM, ATR
2	embryogenesis phenotype	MP:0005380	7.6	FANCA, CDC45, ATM, ATR, CHEK1, RBBP8
3	tumorigenesis	MP:0002006	7.2	RBBP8, H2AFX, IGF1, IGF1R, FANCA, ATM
4	endocrine/exocrine gland phenotype	MP:0005379	6.9	FANCA, IGFBP3, IGF1, H2AFX, MCPH1, MDC1
5	reproductive system phenotype	MP:0005389	6.5	H2AFX, IGF1, IGF1R, FANCA, MCPH1, MDC1
6	cellular phenotype	MP:0005384	6.1	MCPH1, FANCA, IGF1R, IGF1, H2AFX, MDC1
7	growth/size phenotype	MP:0005378	6.1	FANCA, IGF1R, IGFBP3, IGF1, H2AFX, MCPH1
8	mortality/aging	MP:0010768	5.5	MCPH1, FANCA, IGF1R, IGF1, H2AFX, DNM3

Articles related to seckel syndrome:

(show all 12)

id	Title	Authors	Year	Affiliating Genes
1	Novel CENPJ mutation causes Seckel syndrome. (20522431)	Al-Dosari M.S.... Alkuraya F.S.	2010	CENPJ
2	Majewski osteodysplastic primordial dwarfism type II (MOPD II) syndrome previously diagnosed as Seckel syndrome: report of a novel m utation of the PCNT gene. (19839044)	Piane M.... Scarano G.	2009	PCNT
3	Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling. (18157127)	Griffith E.... O'Driscoll M.	2008	PCNT
4	Seckel syndrome associated with oligodontia, microdontia, enamel hypoplasia, delayed eruption, and dentin dysmineralization: a new variant? (17032400)	De Coster P.J.... Vral A.	2006	DSPP
5	An overview of three new disorders associated with genetic instability: LIG4 syndrome, RS-SCID and ATR-Seckel syndrome. (15279811)	O'Driscoll M.... Jeggo P.A.	2004	LIG4, ATR
6	Chromosomal instability at common fragile sites in Seckel syndrome. (15309689)	Casper A.M.... Glover T.W.	2004	ATR
7	Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway. (15496423)	Alderton G.K.... O'Driscoll M.	2004	ATR
8	A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. (12640452)	O'Driscoll M.... Goodship J.A.	2003	LIG4, ATR
9	Growth failure in a child showing characteristics of Seckel syndrome: possible effects of IGF-I and endogenous IGFBP-3. (12153610)	Schmidt A.... Kiess W.	2002	IGF1R, IGF1, IGFBP3
10	A new locus for Seckel syndrome on chromosome 18p11.31-q11.2. (11781686)	Borglum A.D.... Hertz J.M.	2001	SCKL2
11	Autozygosity mapping of a seckel syndrome locus to chromosome 3q22. 1-q24. (10889046)	Goodship J.... Wright M.	2000	ATR
12	Normal expression of the Fanconi anemia proteins FAA and FAC and sensitivity to mitomycin C in two patients with Seckel syndrome. (10232749)	Abou-Zahr F.... Youssoufian H.	1999	FANCA

Genes related to seckel syndrome according to GeneCards:

(show all 24)

id	Symbol	Description	Score	GeneCards Section Context
1	ATR	ataxia telangiectasia and Rad3 related	11.1	Publications, Summaries
2	SCKL2	Seckel syndrome 2	11.1	Publications, Aliases & Descriptions
3	SCKL3	Seckel syndrome 3	11.1	Aliases & Descriptions
4	PCNT	pericentrin	11.1	Publications, Summaries
5	RBBP8	retinoblastoma binding protein 8	11.1	Aliases & Descriptions
6	CENPJ	centromere protein J	11.0	Publications
7	LIG4	ligase IV, DNA, ATP-dependent	11.0	Publications
8	MCPH1	microcephalin 1	11.0
9	CENPL	centromere protein L	11.0	Disorders
10	HTR5A	5-hydroxytryptamine (serotonin) receptor 5A, G protein-coupled	11.0	Disorders
11	CEP152	centrosomal protein 152kDa	11.0
12	MDC1	mediator of DNA-damage checkpoint 1	11.0
13	CDC45	cell division cycle 45 homolog (S. cerevisiae)	11.0
14	FANCA	Fanconi anemia, complementation group A	11.0	Publications
15	H2AFX	H2A histone family, member X	11.0
16	ASPM	asp (abnormal spindle) homolog, microcephaly associated (Drosophila)	11.0
17	DSPP	dentin sialophosphoprotein	11.0	Publications
18	CHEK1	checkpoint kinase 1	11.0
19	IGFBP3	insulin-like growth factor binding protein 3	11.0	Publications
20	CNTLN	centlein, centrosomal protein	11.0
21	DNM3	dynamin 3	11.0
22	IGF1R	insulin-like growth factor 1 receptor	11.0	Publications
23	ATM	ataxia telangiectasia mutated	11.0
24	IGF1	insulin-like growth factor 1 (somatomedin C)	11.0	Publications

Pathways related to seckel syndrome according to GeneDecks:

(show all 25)

id	Pathway	Score	Top Affiliating Genes
1	Loss of Nlp from mitotic centrosomes38	9.8	CENPJ, CEP152, PCNT
2	G2/M DNA damage checkpoint38	9.6	ATM, ATR
3	Fanconis Anaemia Pathway36	9.5	ATR, ATM, FANCA
4	Cell cycle_Role of 14-3-3 proteins in cell cycle regulation41	9.4	ATM, ATR, CHEK1
5	Cell cycle Role of 14-3-3 proteins in cell cycle regulation10	9.3	ATM, ATR, CHEK1
6	DNA damage_Role of Brca1 and Brca2 in DNA repair41	9.3	H2AFX, MDC1, ATM, ATR
7	DNA damage Role of Brca1 and Brca2 in DNA repair10	9.3	H2AFX, MDC1, ATM, ATR
8	DNA damage DNA-damage-induced responses10	9.2	CHEK1, MDC1, ATM, ATR
9	G2-M Phase Transition36	9.2	CHEK1, ATR, ATM
10	DNA damage_DNA-damage-induced responses41	9.2	MDC1, ATM, ATR, CHEK1
11	DNA damage ATM/ATR regulation of G1/S checkpoint10	9.2	CHEK1, ATR, ATM, MDC1
12	DNA damage_ATM/ATR regulation of G1/S checkpoint41	9.2	MDC1, ATM, ATR, CHEK1
13	Chks in Checkpoint Regulation36	9.1	ATM, ATR, CHEK1
14	Transcription_Receptor-mediated HIF regulation41	9.1	IGF1, IGFBP3, IGF1R
15	Transcription Receptor-mediated HIF regulation10	9.1	IGF1, IGFBP3, IGF1R
16	DNA Damage3	9.1	MCPH1, ATM, ATR, CHEK1, RBBP8
17	Cell cycle20	9.1	CDC45, ATM, ATR, CHEK1
18	ATM Pathway36	9.0	H2AFX, MDC1, ATM, CHEK1
19	BRCA1 Pathway36	9.0	FANCA, ATM, ATR, CHEK1, RBBP8
20	Development_IGF-1 receptor signaling41	8.9	IGF1R, IGFBP3, IGF1
21	Cell Cycle / Checkpoint Control3	8.9	MCPH1, CDC45, ATM, ATR, CHEK1
22	Development IGF-RI signaling10	8.6	IGF1R, IGFBP3, IGF1
23	p53 signaling pathway20	8.5	IGF1, IGFBP3, ATM, ATR, CHEK1
24	DNA Repair Mechanisms36	8.5	IGF1, FANCA, ATM, ATR, CHEK1, LIG4
25	p53 Mediated Apoptosis36	8.3	IGF1, IGF1R, ATM, ATR, CHEK1

Compounds related to seckel syndrome according to GeneDecks:

(show all 39)

id	Compound	Score	Top Affiliating Genes
1	iplex32	9.9	IGF1, IGFBP3
2	methylmethanesulfonate32	9.9	CHEK1, ATR, H2AFX
3	cgk 73342	9.9	ATM, ATR
4	oxandrolone32 9 9	11.7	IGF1, IGFBP3
5	disuccinimidyl suberate32	9.7	IGF1R, IGFBP3
6	pq 40142	9.7	IGF1R, IGF1
7	demethylasterriquinone b142	9.6	IGF1R, IGF1
8	nandrolone32 18	10.5	IGFBP3, IGF1
9	podophyllotoxin32	9.5	IGF1, IGF1R
10	mecasermin32 9 9	11.3	IGF1R, IGFBP3, IGF1
11	clomiphene citrate32	9.3	IGF1R, IGFBP3, IGF1
12	lycopene32 18	10.3	IGF1R, IGFBP3, IGF1
13	eb 108932	9.3	IGF1R, IGFBP3, IGF1
14	aphidicolin32	9.2	H2AFX, ATM, ATR, CHEK1
15	hydroxyurea32 9 9	11.2	CHEK1, ATR, ATM, H2AFX
16	raloxifene32 9 9	11.2	IGF1R, IGFBP3, IGF1
17	caffeine32 34 9 18 9	13.2	H2AFX, ATM, ATR, CHEK1
18	camptothecin32 42 9 9	12.2	H2AFX, ATM, ATR, CHEK1
19	octreotide32 42 9 9	12.1	IGF1R, IGFBP3, IGF1
20	ag 102432	9.0	IGF1R, IGF1
21	mitoxantrone32 9 9	11.0	H2AFX, IGF1R, ATM
22	prostaglandin f2alpha32	9.0	IGF1R, IGFBP3, IGF1
23	c-peptide32	8.9	IGF1, IGFBP3, IGF1R
24	topotecan32 9 9	10.9	H2AFX, IGF1, ATM, CHEK1
25	mitomycin c32	8.8	H2AFX, IGF1R, FANCA, ATM
26	nacl32	8.7	DNM3, H2AFX, ATM, CHEK1, LIG4
27	okadaic acid32 42	9.6	IGF1R, CDC45, ATM, ATR, CHEK1
28	etoposide32 42 9 9	11.6	CHEK1, ATR, ATM, IGF1R, H2AFX
29	calcitriol32 42 9 18 9	12.6	DSPP, IGF1, IGFBP3, IGF1R, CHEK1
30	gnrh32	8.3	DNM3, IGF1, IGFBP3, IGF1R
31	phosphoinositide32	8.3	DNM3, H2AFX, IGF1R, ATM, ATR
32	doxorubicin32 34 9 9	11.2	H2AFX, IGFBP3, IGF1R, ATM, CHEK1
33	ly29400232	8.1	H2AFX, IGF1, IGFBP3, IGF1R, ATM
34	alanine32	8.0	DNM3, DSPP, IGFBP3, IGF1R, FANCA, CHEK1
35	cisplatin32 34 9 9	11.0	H2AFX, IGFBP3, IGF1R, FANCA, ATM, CHEK1
36	wortmannin32 42	8.9	H2AFX, IGF1, IGF1R, ATM, ATR, CHEK1
37	glutamine32	7.7	DNM3, IGF1, IGFBP3, IGF1R, ATM
38	phosphatidylinositol32	7.4	DNM3, H2AFX, IGF1, IGF1R, ATM, ATR
39	serine32	6.7	DNM3, DSPP, H2AFX, IGF1, IGFBP3, IGF1R

Cellular components related to seckel syndrome according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	centriole	GO:005814	9.6	CNTLN, PCNT, CENPJ
2	insulin-like growth factor binding protein complex	GO:016942	9.4	IGFBP3, IGF1
3	centrosome	GO:005813	8.8	CNTLN, CDC45, CENPJ, CEP152, CHEK1, PCNT
4	chromosome, telomeric region	GO:000781	8.7	H2AFX, ATM, CHEK1
5	nucleoplasm	GO:005654	7.8	H2AFX, FANCA, MDC1, CDC45, ATM, ATR

Biological processes related to seckel syndrome according to GeneDecks:

(show all 12)

id	Name	GO ID	Score	Top Affiliating Genes
1	DNA damage checkpoint	GO:000077	9.8	H2AFX, ATR, CHEK1
2	cellular response to gamma radiation	GO:071480	9.5	ATR, ATM
3	replicative senescence	GO:090399	9.3	CHEK1, ATR, ATM
4	mitotic cell cycle	GO:000278	9.3	CDC45, CENPL, CENPJ, CEP152, PCNT
5	G2/M transition DNA damage checkpoint	GO:031572	9.2	RBBP8, CHEK1, ATM
6	DNA replication	GO:006260	9.2	IGF1, CDC45, ATR, CHEK1
7	double-strand break repair via homologous recombination	GO:000724	9.2	H2AFX, MDC1, ATM, RBBP8
8	double-strand break repair	GO:006302	9.1	H2AFX, MDC1, ATM, LIG4
9	DNA damage induced protein phosphorylation	GO:006975	9.0	CHEK1, ATM
10	cell cycle checkpoint	GO:000075	8.9	CDC45, ATM, ATR, CHEK1, RBBP8
11	response to DNA damage stimulus	GO:006974	8.9	H2AFX, ATM, ATR, CHEK1
12	DNA repair	GO:006281	8.1	RBBP8, H2AFX, FANCA, MDC1, ATM, ATR

Molecular functions related to seckel syndrome according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	insulin-like growth factor I binding	GO:031994	9.4	IGF1R, IGFBP3
2	protein binding	GO:005515	4.6	PCNT, DNM3, H2AFX, IGF1, IGFBP3, IGF1R