KNO1
MCID: KNB006
MIFTS: 43

Knobloch Syndrome 1 (KNO1)

Categories: Eye diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Knobloch Syndrome 1

MalaCards integrated aliases for Knobloch Syndrome 1:

Name: Knobloch Syndrome 1 57 74 29 6
Knobloch Syndrome, Type 1 57 13 40
Retinal Detachment and Occipital Encephalocele 57 74
Knobloch Syndrome 59 72
Kno1 57 74
Kno 57 74
Retinal Detachment-Occipital Encephalocele Syndrome 59
Knobloch-Layer Syndrome 59
Encephalocele 44

Characteristics:

Orphanet epidemiological data:

59
knobloch syndrome
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Miscellaneous:
phenotypic variability

Inheritance:
autosomal recessive


HPO:

32
knobloch syndrome 1:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare eye diseases


External Ids:

OMIM 57 267750
MESH via Orphanet 45 C537209
ICD10 via Orphanet 34 Q15.8
UMLS via Orphanet 73 C1849409
Orphanet 59 ORPHA1571
UMLS 72 C1849409

Summaries for Knobloch Syndrome 1

OMIM : 57 Knobloch syndrome is an autosomal recessive developmental disorder primarily characterized by typical eye abnormalities, including high myopia, cataracts, dislocated lens, vitreoretinal degeneration, and retinal detachment, with occipital skull defects, which can range from occipital encephalocele to occult cutis aplasia (summary by Aldahmesh et al., 2011). (267750)

MalaCards based summary : Knobloch Syndrome 1, also known as knobloch syndrome, type 1, is related to knobloch syndrome and encephalocele, and has symptoms including seizures and unspecified visual loss. An important gene associated with Knobloch Syndrome 1 is COL18A1 (Collagen Type XVIII Alpha 1 Chain), and among its related pathways/superpathways is Degradation of the extracellular matrix. The drug Liver Extracts has been mentioned in the context of this disorder. Affiliated tissues include eye, liver and bone, and related phenotypes are mental deterioration and nystagmus

UniProtKB/Swiss-Prot : 74 Knobloch syndrome 1: A developmental disorder primarily characterized by typical eye abnormalities, including high myopia, cataracts, dislocated lens, vitreoretinal degeneration, and retinal detachment, with occipital skull defects, which can range from occipital encephalocele to occult cutis aplasia.

Related Diseases for Knobloch Syndrome 1

Diseases in the Knobloch Syndrome family:

Knobloch Syndrome 1

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

(show top 50) (show all 379)
# Related Disease Score Top Affiliating Genes
1 knobloch syndrome 29.6 SLC19A1 MIR6815 COL18A1 ADAMTS18
2 encephalocele 12.9
3 frontal encephalocele 12.6
4 occipital encephalocele 12.6
5 basal encephalocele 12.5
6 parietal encephalocele 12.5
7 nasal encephalocele 12.4
8 isolated encephalocele 12.3
9 laryngeal atresia, encephalocele, and limb deformities 12.3
10 encephalocele anencephaly 12.3
11 meningoencephalocele 12.1
12 dk phocomelia syndrome 12.1
13 meckel syndrome, type 1 11.8
14 radiohumeral fusions with other skeletal and craniofacial anomalies 11.7
15 meckel syndrome, type 3 11.5
16 hydrocephalus 11.5
17 neural tube defects 11.5
18 nasal glial heterotopia 11.4
19 chiari malformation 11.4
20 frontonasal dysplasia 1 11.4
21 dandy-walker complex 11.4
22 vitreoretinal degeneration 11.3
23 boomerang dysplasia 11.2
24 meckel syndrome, type 4 11.2
25 meckel syndrome, type 8 11.2
26 meckel syndrome, type 9 11.2
27 craniotelencephalic dysplasia 11.1
28 frontofacionasal dysplasia 11.1
29 orofaciodigital syndrome iv 11.1
30 meckel syndrome, type 7 11.1
31 roberts syndrome 11.1
32 otopalatodigital syndrome, type ii 11.1
33 oculoauriculofrontonasal syndrome 11.1
34 meckel syndrome, type 2 11.1
35 meckel syndrome, type 5 11.1
36 meckel syndrome, type 6 11.1
37 meckel syndrome, type 10 11.1
38 craniofacial anomalies and anterior segment dysgenesis syndrome 11.1
39 meckel syndrome, type 11 11.1
40 meckel syndrome 12 11.1
41 meckel syndrome 13 11.1
42 midface dysplasia 11.1
43 acrofrontofacionasal dysostosis 11.1
44 amniotic band syndrome 11.1
45 schisis association 11.1
46 cranial meningocele 10.7
47 congenital hydrocephalus 10.7
48 hypertelorism 10.6
49 exophthalmos 10.5
50 meningitis 10.5

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



Diseases related to Knobloch Syndrome 1

Symptoms & Phenotypes for Knobloch Syndrome 1

Human phenotypes related to Knobloch Syndrome 1:

32 59 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 mental deterioration 32 occasional (7.5%) HP:0001268
2 nystagmus 59 32 Frequent (79-30%) HP:0000639
3 seizures 59 32 Occasional (29-5%) HP:0001250
4 retinal detachment 59 32 Very frequent (99-80%) HP:0000541
5 visual loss 59 32 Frequent (79-30%) HP:0000572
6 occipital encephalocele 59 32 Very frequent (99-80%) HP:0002085
7 hydrocephalus 59 Frequent (79-30%)
8 ataxia 32 HP:0001251
9 cataract 59 Occasional (29-5%)
10 depressed nasal bridge 59 Occasional (29-5%)
11 strabismus 59 Occasional (29-5%)
12 patent ductus arteriosus 59 Occasional (29-5%)
13 joint hyperflexibility 59 Occasional (29-5%)
14 epicanthus 59 Occasional (29-5%)
15 progressive visual loss 59 Frequent (79-30%)
16 myopia 59 Very frequent (99-80%)
17 ventriculomegaly 32 HP:0002119
18 vesicoureteral reflux 59 Occasional (29-5%)
19 ectopia lentis 59 Occasional (29-5%)
20 macular degeneration 59 Very frequent (99-80%)
21 skull defect 59 Very frequent (99-80%)
22 midface retrusion 59 Occasional (29-5%)
23 pyloric stenosis 59 Occasional (29-5%)
24 abnormality of the vitreous humor 59 Frequent (79-30%)
25 abnormality of the hair 59 Occasional (29-5%)
26 polymicrogyria 32 HP:0002126
27 cerebellar atrophy 32 HP:0001272
28 dextrocardia 59 Occasional (29-5%)
29 phthisis bulbi 32 HP:0000667
30 lymphangioma 59 Occasional (29-5%)
31 cerebral atrophy 32 HP:0002059
32 macular hypoplasia 32 HP:0001104
33 vitreoretinal degeneration 59 Frequent (79-30%)
34 high myopia 32 HP:0011003
35 bifid ureter 59 Occasional (29-5%)
36 band keratopathy 32 HP:0000585
37 vitreoretinopathy 32 HP:0007773
38 developmental cataract 32 HP:0000519
39 peripapillary atrophy 32 HP:0500087

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
visual loss
phthisis bulbi
macular hypoplasia
vitreoretinal degeneration
more
Skeletal Skull:
midline occipital bone defect

Neurologic Central Nervous System:
seizures
polymicrogyria
occipital encephalocele
ventricular dilatation
occipital dermal sinus tract
more
Skin Nails Hair Hair:
alopecia at the occipital defect

Clinical features from OMIM:

267750

UMLS symptoms related to Knobloch Syndrome 1:


seizures, unspecified visual loss

Drugs & Therapeutics for Knobloch Syndrome 1

Drugs for Knobloch Syndrome 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Liver Extracts

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Assessment of the Prevalence and Mutational Spectrum of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome and Cerebello-oculo-renal Syndromes Completed NCT00873678
2 Clinical and Molecular Investigations Into Ciliopathies Recruiting NCT00068224

Search NIH Clinical Center for Knobloch Syndrome 1

Cochrane evidence based reviews: encephalocele

Genetic Tests for Knobloch Syndrome 1

Genetic tests related to Knobloch Syndrome 1:

# Genetic test Affiliating Genes
1 Knobloch Syndrome 1 29 COL18A1

Anatomical Context for Knobloch Syndrome 1

MalaCards organs/tissues related to Knobloch Syndrome 1:

41
Eye, Liver, Bone, Brain

Publications for Knobloch Syndrome 1

Articles related to Knobloch Syndrome 1:

(show all 22)
# Title Authors PMID Year
1
No evidence for locus heterogeneity in Knobloch syndrome. 8 71
23667181 2013
2
Deep sequencing reveals 50 novel genes for recessive cognitive disorders. 8 71
21937992 2011
3
Identification of ADAMTS18 as a gene mutated in Knobloch syndrome. 8 71
21862674 2011
4
Collagen XVIII mutation in Knobloch syndrome with acute lymphoblastic leukemia. 8 71
20799329 2010
5
Locus heterogeneity and Knobloch syndrome. 8 71
20979194 2010
6
Homozygosity mapping through whole genome analysis identifies a COL18A1 mutation in an Indian family presenting with an autosomal recessive neurological disorder. 8 71
19160445 2009
7
Mapping of a novel type III variant of Knobloch syndrome (KNO3) to chromosome 17q11.2. 8 71
17975799 2007
8
CNS malformations in Knobloch syndrome with splice mutation in COL18A1 gene. 8 71
17546652 2007
9
Knobloch syndrome: novel mutations in COL18A1, evidence for genetic heterogeneity, and a functionally impaired polymorphism in endostatin. 8 71
14695535 2004
10
Collagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor growth, plays a critical role in the maintenance of retinal structure and in neural tube closure (Knobloch syndrome). 8 71
10942434 2000
11
The second report of Knobloch syndrome. 8 71
1554013 1992
12
Brain malformations associated with Knobloch syndrome--review of literature, expanding clinical spectrum, and identification of novel mutations. 8
25456301 2014
13
Evidence of neuronal migration disorders in Knobloch syndrome: clinical and molecular analysis of two novel families. 8
12707952 2003
14
Molecular analysis of collagen XVIII reveals novel mutations, presence of a third isoform, and possible genetic heterogeneity in Knobloch syndrome. 71
12415512 2002
15
Knobloch syndrome involving midline scalp defect of the frontal region. 8
10607954 2000
16
Report of two sibs with Knobloch syndrome (encephalocoele and viteroretinal degeneration) and other anomalies. 8
9677068 1998
17
A gene which causes severe ocular alterations and occipital encephalocele (Knobloch syndrome) is mapped to 21q22.3. 8
8776601 1996
18
Knobloch syndrome in a large Brazilian consanguineous family: confirmation of autosomal recessive inheritance. 8
7802003 1994
19
Congenital scalp defects and vitreoretinal degeneration: redefining the Knobloch syndrome. 8
8484411 1993
20
Syndromes with cephaloceles. 8
7101196 1982
21
Hydrocephalus, agyria, retinal dysplasia, encephalocele (HARD +/- E) syndrome: an autosomal recessive condition. 8
728564 1978
22
Drosophila type XV/XVIII collagen mutants manifest integrin mediated mitochondrial dysfunction, which is improved by cyclosporin A and losartan. 38
23454281 2013

Variations for Knobloch Syndrome 1

ClinVar genetic disease variations for Knobloch Syndrome 1:

6 (show top 50) (show all 156)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 COL18A1 NM_030582.4(COL18A1): c.3213dup (p.Gly1072fs) duplication Pathogenic rs749009747 21:46917565-46917565 21:45497651-45497651
2 COL18A1 NM_030582.4(COL18A1): c.1610dup (p.Gly538fs) duplication Pathogenic rs1555860555 21:46897722-46897723 21:45477808-45477809
3 COL18A1 NM_030582.4(COL18A1): c.4490_4491insTGCC (p.Cys1498fs) insertion Pathogenic rs1555877107 21:46932251-46932252 21:45512337-45512338
4 COL18A1 COL18A1, IVS1AS, A-T, -2 single nucleotide variant Pathogenic
5 COL18A1 COL18A1, 2-BP DEL, 3514CT deletion Pathogenic
6 COL18A1 NM_030582.4(COL18A1): c.3363dup (p.Gly1122fs) duplication Pathogenic rs769882681 21:46924425-46924425 21:45504511-45504511
7 COL18A1 COL18A1, IVS36DS, A-C, +3 single nucleotide variant Pathogenic
8 COL18A1 COL18A1, 2-BP DEL, 3617CT deletion Pathogenic
9 COL18A1 COL18A1, 2-BP DEL deletion Pathogenic
10 COL18A1 NM_030582.4(COL18A1): c.4054_4055del (p.Leu1352fs) deletion Pathogenic rs398122391 21:46930005-46930006 21:45510091-45510092
11 COL18A1 NM_130445.2(COL18A1): c.2118dupC (p.Gly707Argfs) duplication Pathogenic rs775168204 21:46911189-46911189 21:45491275-45491275
12 COL18A1 NM_030582.4(COL18A1): c.4349+2T> C single nucleotide variant Pathogenic 21:46931142-46931142 21:45511228-45511228
13 COL18A1 NM_030582.4(COL18A1): c.3509_3518del (p.Pro1170fs) deletion Pathogenic 21:46925157-46925166 21:45505243-45505252
14 COL18A1 NM_030582.4(COL18A1): c.2153G> T (p.Gly718Val) single nucleotide variant Likely pathogenic rs1114167359 21:46901878-46901878 21:45481964-45481964
15 COL18A1 NM_030582.4(COL18A1): c.1993-6G> A single nucleotide variant Conflicting interpretations of pathogenicity rs200886865 21:46900608-46900608 21:45480694-45480694
16 COL18A1 NM_030582.4(COL18A1): c.2215-6G> A single nucleotide variant Conflicting interpretations of pathogenicity rs142726108 21:46902703-46902703 21:45482789-45482789
17 COL18A1 NM_030582.4(COL18A1): c.1144G> A (p.Gly382Arg) single nucleotide variant Uncertain significance rs373735265 21:46888653-46888653 21:45468739-45468739
18 COL18A1 NM_030582.4(COL18A1): c.1153G> A (p.Val385Met) single nucleotide variant Uncertain significance rs201116208 21:46888662-46888662 21:45468748-45468748
19 COL18A1 NM_030582.4(COL18A1): c.1320G> C (p.Glu440Asp) single nucleotide variant Uncertain significance rs560442019 21:46895431-46895431 21:45475517-45475517
20 ADAMTS18 NM_199355.4(ADAMTS18): c.536C> T (p.Ser179Leu) single nucleotide variant Uncertain significance rs387906972 16:77401580-77401580 16:77367683-77367683
21 COL18A1 NM_030582.4(COL18A1): c.646+587C> A single nucleotide variant Uncertain significance rs764709181 21:46876677-46876677 21:45456763-45456763
22 COL18A1 NM_030582.4(COL18A1): c.2571+9C> T single nucleotide variant Uncertain significance rs780751282 21:46910269-46910269 21:45490355-45490355
23 COL18A1 NM_030582.4(COL18A1): c.2625C> T (p.Asp875=) single nucleotide variant Uncertain significance rs373006940 21:46911156-46911156 21:45491242-45491242
24 COL18A1 NM_030582.4(COL18A1): c.2688G> A (p.Ser896=) single nucleotide variant Uncertain significance rs374522196 21:46911219-46911219 21:45491305-45491305
25 COL18A1 NM_030582.4(COL18A1): c.757G> A (p.Asp253Asn) single nucleotide variant Uncertain significance rs370054491 21:46888266-46888266 21:45468352-45468352
26 COL18A1 NM_030582.4(COL18A1): c.*30G> A single nucleotide variant Uncertain significance rs373537387 21:46932342-46932342 21:45512428-45512428
27 COL18A1 NM_030582.4(COL18A1): c.2920-15C> T single nucleotide variant Uncertain significance rs754575228 21:46914761-46914761 21:45494847-45494847
28 COL18A1 NM_030582.4(COL18A1): c.2969G> A (p.Arg990Gln) single nucleotide variant Uncertain significance rs751578852 21:46914825-46914825 21:45494911-45494911
29 COL18A1 NM_030582.4(COL18A1): c.3117+9C> T single nucleotide variant Uncertain significance rs774784084 21:46916491-46916491 21:45496577-45496577
30 COL18A1 NM_030582.4(COL18A1): c.3172C> T (p.Pro1058Ser) single nucleotide variant Uncertain significance rs377290522 21:46917524-46917524 21:45497610-45497610
31 COL18A1 NM_030582.4(COL18A1): c.3223+11C> G single nucleotide variant Uncertain significance rs886057128 21:46917586-46917586 21:45497672-45497672
32 COL18A1 NM_030582.4(COL18A1): c.3328G> A (p.Gly1110Ser) single nucleotide variant Uncertain significance rs771054336 21:46924390-46924390 21:45504476-45504476
33 COL18A1 NM_030582.4(COL18A1): c.3363C> A (p.Pro1121=) single nucleotide variant Uncertain significance rs543392161 21:46924425-46924425 21:45504511-45504511
34 COL18A1 NM_030582.4(COL18A1): c.3320_3321insT (p.Gly1108fs) insertion Uncertain significance 21:46924382-46924382 21:45504468-45504469
35 COL18A1 NM_030582.4(COL18A1): c.*342C> G single nucleotide variant Uncertain significance rs886057139 21:46932654-46932654 21:45512740-45512740
36 COL18A1 NM_030582.4(COL18A1): c.*369C> T single nucleotide variant Uncertain significance rs886057140 21:46932681-46932681 21:45512767-45512767
37 COL18A1 NM_030582.4(COL18A1): c.*484C> T single nucleotide variant Uncertain significance rs548084117 21:46932796-46932796 21:45512882-45512882
38 COL18A1 NM_030582.4(COL18A1): c.*584C> A single nucleotide variant Uncertain significance rs886057143 21:46932896-46932896 21:45512982-45512982
39 COL18A1 NM_030582.4(COL18A1): c.*1203A> G single nucleotide variant Uncertain significance rs886057147 21:46933515-46933515 21:45513601-45513601
40 COL18A1 NM_030582.4(COL18A1): c.*849A> T single nucleotide variant Uncertain significance rs17255379 21:46933161-46933161 21:45513247-45513247
41 COL18A1 NM_030582.4(COL18A1): c.*851C> T single nucleotide variant Uncertain significance rs886057145 21:46933163-46933163 21:45513249-45513249
42 COL18A1 NM_030582.4(COL18A1): c.*1088C> T single nucleotide variant Uncertain significance rs756987643 21:46933400-46933400 21:45513486-45513486
43 COL18A1 NM_030582.4(COL18A1): c.*1157C> G single nucleotide variant Uncertain significance rs527507454 21:46933469-46933469 21:45513555-45513555
44 COL18A1 NM_030582.4(COL18A1): c.3495_3503CCCCCCAGG[1] (p.1162_1164GPP[3]) short repeat Uncertain significance 21:46925152-46925160 21:45505238-45505246
45 COL18A1 NM_030582.4(COL18A1): c.1278+5_1278+8del short repeat Uncertain significance 21:46893896-46893899 21:45473986-45473989
46 COL18A1 NM_030582.4(COL18A1): c.515G> A (p.Arg172His) single nucleotide variant Uncertain significance rs200284308 21:46875959-46875959 21:45456045-45456045
47 COL18A1 NM_030582.4(COL18A1): c.*302C> A single nucleotide variant Uncertain significance rs17255281 21:46932614-46932614 21:45512700-45512700
48 COL18A1 NM_030582.4(COL18A1): c.*498G> A single nucleotide variant Uncertain significance rs555167805 21:46932810-46932810 21:45512896-45512896
49 COL18A1 NM_030582.4(COL18A1): c.*532T> C single nucleotide variant Uncertain significance rs560265269 21:46932844-46932844 21:45512930-45512930
50 COL18A1 NM_030582.4(COL18A1): c.1930G> A (p.Asp644Asn) single nucleotide variant Uncertain significance rs61738822 21:46900062-46900062 21:45480148-45480148

Expression for Knobloch Syndrome 1

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

Pathways for Knobloch Syndrome 1

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.28 COL18A1 ADAMTS18

GO Terms for Knobloch Syndrome 1

Sources for Knobloch Syndrome 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
Content
Loading form....