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 73 29 6
Knobloch Syndrome, Type 1 57 13 39
Retinal Detachment and Occipital Encephalocele 57 73
Knobloch Syndrome 58 71
Kno1 57 73
Kno 57 73
Retinal Detachment-Occipital Encephalocele Syndrome 58
Knobloch-Layer Syndrome 58
Encephalocele 44

Characteristics:

Orphanet epidemiological data:

58
knobloch syndrome
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
inter- and intrafamilial phenotypic variability


HPO:

31
knobloch syndrome 1:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare eye diseases


External Ids:

OMIM® 57 267750
MESH via Orphanet 45 C537209
ICD10 via Orphanet 33 Q15.8
UMLS via Orphanet 72 C1849409
Orphanet 58 ORPHA1571
UMLS 71 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) (Updated 05-Mar-2021)

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. Affiliated tissues include eye, bone and brain, and related phenotypes are mental deterioration and nystagmus

UniProtKB/Swiss-Prot : 73 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 354)
# Related Disease Score Top Affiliating Genes
1 knobloch syndrome 30.5 SLC19A1 COL18A1 ADAMTS18
2 encephalocele 11.7
3 occipital encephalocele 11.3
4 meningoencephalocele 11.3
5 frontal encephalocele 11.3
6 dk phocomelia syndrome 11.3
7 meckel syndrome, type 1 11.2
8 basal encephalocele 11.2
9 radiohumeral fusions with other skeletal and craniofacial anomalies 11.1
10 parietal encephalocele 11.1
11 nasal encephalocele 11.0
12 isolated encephalocele 11.0
13 dandy-walker syndrome 11.0
14 hydrocephalus 11.0
15 meckel syndrome, type 3 11.0
16 boomerang dysplasia 11.0
17 oculoauriculofrontonasal syndrome 11.0
18 meckel syndrome, type 4 11.0
19 meckel syndrome, type 8 11.0
20 meckel syndrome, type 9 11.0
21 meckel syndrome 13 11.0
22 vitreoretinal degeneration 10.9
23 neural tube defects 10.9
24 encephalocele anencephaly 10.9
25 laryngeal atresia, encephalocele, and limb deformities 10.9
26 nasal glial heterotopia 10.9
27 chiari malformation 10.9
28 frontonasal dysplasia 1 10.9
29 constricting bands, congenital 10.9
30 craniotelencephalic dysplasia 10.8
31 dyssegmental dysplasia, silverman-handmaker type 10.8
32 frontofacionasal dysplasia 10.8
33 orofaciodigital syndrome iv 10.8
34 meckel syndrome, type 7 10.8
35 roberts-sc phocomelia syndrome 10.8
36 otopalatodigital syndrome, type ii 10.8
37 meckel syndrome, type 2 10.8
38 meckel syndrome, type 5 10.8
39 meckel syndrome, type 6 10.8
40 meckel syndrome, type 10 10.8
41 craniofacial anomalies and anterior segment dysgenesis syndrome 10.8
42 meckel syndrome, type 11 10.8
43 meckel syndrome 12 10.8
44 midface dysplasia 10.8
45 acrofrontofacionasal dysostosis 10.8
46 schisis association 10.8
47 hypertelorism 10.4
48 cranial meningocele 10.4
49 exophthalmos 10.3
50 meningitis 10.3

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:

31 58 (show all 41)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 mental deterioration 31 occasional (7.5%) HP:0001268
2 nystagmus 58 31 Frequent (79-30%) HP:0000639
3 retinal detachment 58 31 Very frequent (99-80%) HP:0000541
4 occipital encephalocele 58 31 Very frequent (99-80%) HP:0002085
5 visual loss 58 31 Frequent (79-30%) HP:0000572
6 seizures 58 Occasional (29-5%)
7 ataxia 31 HP:0001251
8 hydrocephalus 58 Frequent (79-30%)
9 cataract 58 Occasional (29-5%)
10 depressed nasal bridge 58 Occasional (29-5%)
11 progressive visual loss 58 Frequent (79-30%)
12 strabismus 58 Occasional (29-5%)
13 epicanthus 58 Occasional (29-5%)
14 myopia 58 Very frequent (99-80%)
15 alopecia 31 HP:0001596
16 ectopia lentis 58 Occasional (29-5%)
17 patent ductus arteriosus 58 Occasional (29-5%)
18 vesicoureteral reflux 58 Occasional (29-5%)
19 ventriculomegaly 31 HP:0002119
20 joint hyperflexibility 58 Occasional (29-5%)
21 skull defect 58 Very frequent (99-80%)
22 pyloric stenosis 58 Occasional (29-5%)
23 abnormal vitreous humor morphology 58 Frequent (79-30%)
24 midface retrusion 58 Occasional (29-5%)
25 polymicrogyria 31 HP:0002126
26 abnormality of the hair 58 Occasional (29-5%)
27 dextrocardia 58 Occasional (29-5%)
28 phthisis bulbi 31 HP:0000667
29 cerebellar atrophy 31 HP:0001272
30 macular hypoplasia 31 HP:0001104
31 vitreoretinal degeneration 58 Frequent (79-30%)
32 cerebral atrophy 31 HP:0002059
33 macular degeneration 58 Very frequent (99-80%)
34 lymphangioma 58 Occasional (29-5%)
35 high myopia 31 HP:0011003
36 developmental cataract 31 HP:0000519
37 bifid ureter 58 Occasional (29-5%)
38 vitreoretinopathy 31 HP:0007773
39 band keratopathy 31 HP:0000585
40 peripapillary atrophy 31 HP:0500087
41 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Central Nervous System:
seizures
polymicrogyria
occipital encephalocele
ventricular dilatation
occipital dermal sinus tract
more
Skeletal:
hypermobile joints

Genitourinary Ureters:
bifid ureters
ureteric anomaly

Skin Nails Hair Hair:
alopecia at the occipital defect

Head And Neck Eyes:
nystagmus
lens subluxation
phthisis bulbi
macular hypoplasia
vitreoretinal degeneration
more
Genitourinary Kidneys:
congenital hydronephrosis
duplex kidneys

Skeletal Skull:
midline occipital bone defect

Clinical features from OMIM®:

267750 (Updated 05-Mar-2021)

UMLS symptoms related to Knobloch Syndrome 1:


seizures, unspecified visual loss

MGI Mouse Phenotypes related to Knobloch Syndrome 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 renal/urinary system MP:0005367 8.8 ADAMTS18 COL18A1 SLC19A1

Drugs & Therapeutics for Knobloch Syndrome 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Prospective Longitudinal Quality of Life Study in Patients Undergoing Endoscopic Endonasal Skull Base Surgery Recruiting NCT04087902

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:

40
Eye, Bone, Brain

Publications for Knobloch Syndrome 1

Articles related to Knobloch Syndrome 1:

(show all 24)
# Title Authors PMID Year
1
COL18A1 is a candidate eye iridocorneal angle-closure gene in humans. 57 6
30007336 2018
2
No evidence for locus heterogeneity in Knobloch syndrome. 57 6
23667181 2013
3
Deep sequencing reveals 50 novel genes for recessive cognitive disorders. 6 57
21937992 2011
4
Locus heterogeneity and Knobloch syndrome. 57 6
20979194 2010
5
Collagen XVIII mutation in Knobloch syndrome with acute lymphoblastic leukemia. 57 6
20799329 2010
6
Homozygosity mapping through whole genome analysis identifies a COL18A1 mutation in an Indian family presenting with an autosomal recessive neurological disorder. 6 57
19160445 2009
7
Mapping of a novel type III variant of Knobloch syndrome (KNO3) to chromosome 17q11.2. 6 57
17975799 2007
8
CNS malformations in Knobloch syndrome with splice mutation in COL18A1 gene. 6 57
17546652 2007
9
Knobloch syndrome: novel mutations in COL18A1, evidence for genetic heterogeneity, and a functionally impaired polymorphism in endostatin. 6 57
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). 6 57
10942434 2000
11
The second report of Knobloch syndrome. 57 6
1554013 1992
12
Molecular and Clinical Findings in Patients With Knobloch Syndrome. 57
27259167 2016
13
Brain malformations associated with Knobloch syndrome--review of literature, expanding clinical spectrum, and identification of novel mutations. 57
25456301 2014
14
Identification of ADAMTS18 as a gene mutated in Knobloch syndrome. 57
21862674 2011
15
Evidence of neuronal migration disorders in Knobloch syndrome: clinical and molecular analysis of two novel families. 57
12707952 2003
16
Molecular analysis of collagen XVIII reveals novel mutations, presence of a third isoform, and possible genetic heterogeneity in Knobloch syndrome. 6
12415512 2002
17
Knobloch syndrome involving midline scalp defect of the frontal region. 57
10607954 2000
18
Report of two sibs with Knobloch syndrome (encephalocoele and viteroretinal degeneration) and other anomalies. 57
9677068 1998
19
A gene which causes severe ocular alterations and occipital encephalocele (Knobloch syndrome) is mapped to 21q22.3. 57
8776601 1996
20
Knobloch syndrome in a large Brazilian consanguineous family: confirmation of autosomal recessive inheritance. 57
7802003 1994
21
Congenital scalp defects and vitreoretinal degeneration: redefining the Knobloch syndrome. 57
8484411 1993
22
Syndromes with cephaloceles. 57
7101196 1982
23
Hydrocephalus, agyria, retinal dysplasia, encephalocele (HARD +/- E) syndrome: an autosomal recessive condition. 57
728564 1978
24
Drosophila type XV/XVIII collagen mutants manifest integrin mediated mitochondrial dysfunction, which is improved by cyclosporin A and losartan. 61
23454281 2013

Variations for Knobloch Syndrome 1

ClinVar genetic disease variations for Knobloch Syndrome 1:

6 (show top 50) (show all 243)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 COL18A1 COL18A1, IVS1AS, A-T, -2 SNV Pathogenic 17115
2 COL18A1 COL18A1, 2-BP DEL, 3514CT Deletion Pathogenic 17116
3 COL18A1 NM_030582.4(COL18A1):c.3363dup (p.Gly1122fs) Duplication Pathogenic 17117 rs769882681 21:46924418-46924419 21:45504504-45504505
4 COL18A1 COL18A1, IVS36DS, A-C, +3 SNV Pathogenic 17119
5 COL18A1 COL18A1, 2-BP DEL, 3617CT Deletion Pathogenic 29652
6 COL18A1 COL18A1, 2-BP DEL Deletion Pathogenic 29653
7 COL18A1 NM_030582.4(COL18A1):c.4054_4055del (p.Leu1352fs) Deletion Pathogenic 65410 rs398122391 21:46930005-46930006 21:45510091-45510092
8 COL18A1 NM_030582.4(COL18A1):c.3213dup (p.Gly1072fs) Duplication Pathogenic 403722 rs749009747 21:46917558-46917559 21:45497644-45497645
9 COL18A1 NM_030582.4(COL18A1):c.1610dup (p.Gly538fs) Duplication Pathogenic 548656 rs1555860555 21:46897722-46897723 21:45477808-45477809
10 COL18A1 NM_030582.4(COL18A1):c.4490_4491insTGCC (p.Cys1498fs) Insertion Pathogenic 548657 rs1555877107 21:46932251-46932252 21:45512337-45512338
11 COL18A1 NM_030582.4(COL18A1):c.4349+2T>C SNV Pathogenic 623178 rs113847452 21:46931142-46931142 21:45511228-45511228
12 COL18A1 NM_030582.4(COL18A1):c.3509_3518del (p.Pro1170fs) Deletion Pathogenic 623349 rs756797124 21:46925150-46925159 21:45505236-45505245
13 COL18A1 NM_030582.4(COL18A1):c.4053_4054del (p.Leu1352fs) Deletion Pathogenic 684620 rs1602651770 21:46930001-46930002 21:45510087-45510088
14 COL18A1 NM_030582.4(COL18A1):c.969dup (p.Ala324fs) Duplication Pathogenic 812292 rs1602456821 21:46888477-46888478 21:45468563-45468564
15 COL18A1 NM_030582.4(COL18A1):c.808del (p.Arg270fs) Deletion Pathogenic 872909
16 COL18A1 NM_030582.4(COL18A1):c.1129del (p.Leu377fs) Deletion Pathogenic 872910
17 COL18A1 NM_030582.4(COL18A1):c.1698del (p.Gly567fs) Deletion Pathogenic 915433 21:46897813-46897813 21:45477899-45477899
18 COL18A1 NM_001379500.1(COL18A1):c.3532_3533del (p.Gly1178fs) Deletion Pathogenic 976335 21:46930014-46930015 21:45510100-45510101
19 COL18A1 NM_130445.2(COL18A1):c.2118dupC (p.Gly707Argfs) Duplication Pathogenic 65411 rs775168204 21:46911182-46911183 21:45491268-45491269
20 COL18A1 NM_030582.4(COL18A1):c.2416C>T (p.Arg806Ter) SNV Likely pathogenic 915432 21:46907403-46907403 21:45487489-45487489
21 COL18A1 NM_030582.4(COL18A1):c.3772C>T (p.Arg1258Ter) SNV Likely pathogenic 666965 rs771752014 21:46927499-46927499 21:45507585-45507585
22 COL18A1 NM_030582.4(COL18A1):c.4355_4356TG[1] (p.Trp1453fs) Microsatellite Likely pathogenic 800861 rs1602667345 21:46932115-46932116 21:45512201-45512202
23 COL18A1 NM_030582.4(COL18A1):c.2153G>T (p.Gly718Val) SNV Likely pathogenic 427899 rs1114167359 21:46901878-46901878 21:45481964-45481964
24 COL18A1 NM_030582.4(COL18A1):c.3495_3503CCCCCCAGG[1] (p.1162_1164GPP[3]) Microsatellite Uncertain significance 587462 rs759403198 21:46925141-46925149 21:45505227-45505235
25 COL18A1 NM_194255.4(SLC19A1):c.*2057T>C SNV Uncertain significance 340303 rs886057147 21:46933515-46933515 21:45513601-45513601
26 COL18A1 NM_030582.4(COL18A1):c.646+587C>A SNV Uncertain significance 548501 rs764709181 21:46876677-46876677 21:45456763-45456763
27 COL18A1 NM_030582.4(COL18A1):c.515G>A (p.Arg172His) SNV Uncertain significance 447131 rs200284308 21:46875959-46875959 21:45456045-45456045
28 COL18A1 NM_030582.4(COL18A1):c.3320_3321insT (p.Gly1108fs) Insertion Uncertain significance 632383 rs771218061 21:46924382-46924383 21:45504468-45504469
29 COL18A1 NM_030582.4(COL18A1):c.3430C>T (p.Pro1144Ser) SNV Uncertain significance 340261 rs761528498 21:46925078-46925078 21:45505164-45505164
30 COL18A1 NM_030582.4(COL18A1):c.2047G>A (p.Gly683Ser) SNV Uncertain significance 340223 rs368194132 21:46900668-46900668 21:45480754-45480754
31 COL18A1 NM_030582.4(COL18A1):c.3118-12C>T SNV Uncertain significance 340249 rs201057172 21:46916952-46916952 21:45497038-45497038
32 COL18A1 NM_030582.4(COL18A1):c.2526C>T (p.Pro842=) SNV Uncertain significance 340231 rs754862849 21:46910215-46910215 21:45490301-45490301
33 COL18A1 NM_030582.4(COL18A1):c.2974-8C>T SNV Uncertain significance 340246 rs367814420 21:46915264-46915264 21:45495350-45495350
34 COL18A1 NM_030582.4(COL18A1):c.4079G>A (p.Arg1360His) SNV Uncertain significance 340267 rs770331440 21:46930030-46930030 21:45510116-45510116
35 COL18A1 NM_194255.4(SLC19A1):c.*2870C>T SNV Uncertain significance 340286 rs760605806 21:46932702-46932702 21:45512788-45512788
36 COL18A1 NM_194255.4(SLC19A1):c.*2755C>T SNV Uncertain significance 340289 rs886057141 21:46932817-46932817 21:45512903-45512903
37 COL18A1 NM_030582.4(COL18A1):c.2478G>T (p.Val826=) SNV Uncertain significance 340230 rs886057125 21:46909414-46909414 21:45489500-45489500
38 COL18A1 NM_030582.4(COL18A1):c.2247C>T (p.Ser749=) SNV Uncertain significance 340228 rs559725056 21:46906780-46906780 21:45486866-45486866
39 COL18A1 NM_030582.4(COL18A1):c.1536C>T (p.Arg512=) SNV Uncertain significance 340209 rs530808102 21:46897392-46897392 21:45477478-45477478
40 COL18A1 NM_030582.4(COL18A1):c.3561C>T (p.Gly1187=) SNV Uncertain significance 340263 rs886057129 21:46925288-46925288 21:45505374-45505374
41 COL18A1 NM_030582.4(COL18A1):c.1599G>A (p.Arg533=) SNV Uncertain significance 340212 rs886057123 21:46897717-46897717 21:45477803-45477803
42 COL18A1 NM_030582.4(COL18A1):c.2969G>A (p.Arg990Gln) SNV Uncertain significance 340245 rs751578852 21:46914825-46914825 21:45494911-45494911
43 COL18A1 NM_030582.4(COL18A1):c.3117+9C>T SNV Uncertain significance 340248 rs774784084 21:46916491-46916491 21:45496577-45496577
44 COL18A1 NM_030582.4(COL18A1):c.4296C>T (p.Arg1432=) SNV Uncertain significance 340272 rs886057135 21:46931096-46931096 21:45511182-45511182
45 COL18A1 NM_194255.4(SLC19A1):c.*2762C>T SNV Uncertain significance 340288 rs555167805 21:46932810-46932810 21:45512896-45512896
46 COL18A1 NM_030582.4(COL18A1):c.3233C>T (p.Pro1078Leu) SNV Uncertain significance 340254 rs201753320 21:46923934-46923934 21:45504020-45504020
47 COL18A1 NM_030582.4(COL18A1):c.1233G>A (p.Val411=) SNV Uncertain significance 340201 rs149772252 21:46893850-46893850 21:45473936-45473936
48 COL18A1 NM_030582.4(COL18A1):c.4189G>A (p.Ala1397Thr) SNV Uncertain significance 340269 rs886057133 21:46930140-46930140 21:45510226-45510226
49 COL18A1 NM_030582.4(COL18A1):c.3163A>G (p.Asn1055Asp) SNV Uncertain significance 340251 rs371993501 21:46917515-46917515 21:45497601-45497601
50 COL18A1 NM_030582.4(COL18A1):c.2625C>T (p.Asp875=) SNV Uncertain significance 340236 rs373006940 21:46911156-46911156 21:45491242-45491242

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

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

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix GO:0031012 8.62 COL18A1 ADAMTS18

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

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix organization GO:0030198 8.62 COL18A1 ADAMTS18

Sources for Knobloch Syndrome 1

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 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....