MCID: KNB001
MIFTS: 38

Knobloch Syndrome

Categories: Eye diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Knobloch Syndrome

MalaCards integrated aliases for Knobloch Syndrome:

Name: Knobloch Syndrome 20 43 36 54 6 71
Retinal Detachment-Occipital Encephalocele Syndrome 20
Retinal Detachment and Occipital Encephalocele 43
Myopia Retinal Detachment Encephalocele 20
Knobloch-Layer Syndrome 20

Classifications:



Summaries for Knobloch Syndrome

MedlinePlus Genetics : 43 Knobloch syndrome is a rare condition characterized by severe vision problems and a skull defect.A characteristic feature of Knobloch syndrome is extreme nearsightedness (high myopia). In addition, several other eye abnormalities are common in people with this condition. Most affected individuals have vitreoretinal degeneration, which is breakdown (degeneration) of two structures in the eye called the vitreous and the retina. The vitreous is the gelatin-like substance that fills the eye, and the retina is the light-sensitive tissue at the back of the eye. Vitreoretinal degeneration often leads to separation of the retina from the back of the eye (retinal detachment). Affected individuals may also have abnormalities in the central area of the retina, called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. Due to abnormalities in the vitreous, retina, and macula, people with Knobloch syndrome often develop blindness in one or both eyes.Another characteristic feature of Knobloch syndrome is a skull defect called an occipital encephalocele, which is a sac-like protrusion of the brain (encephalocele) through a defect in the bone at the base of the skull (occipital bone). Some affected individuals have been diagnosed with a different skull defect in the occipital region, and it is unclear whether the defect is always a true encephalocele. In other conditions, encephaloceles may be associated with intellectual disability; however, most people with Knobloch syndrome have normal intelligence.

MalaCards based summary : Knobloch Syndrome, also known as retinal detachment-occipital encephalocele syndrome, is related to knobloch syndrome 1 and vitreoretinal degeneration, and has symptoms including seizures and unspecified visual loss. An important gene associated with Knobloch Syndrome is COL18A1 (Collagen Type XVIII Alpha 1 Chain), and among its related pathways/superpathways is Degradation of the extracellular matrix. Affiliated tissues include eye, retina and skin, and related phenotypes are myopia and retinal detachment

GARD : 20 Knobloch syndrome is characterized by severe vision problems and skull defects. The most common features include extreme nearsightedness (high myopia), recurrent retinal detachment, and occipital encephalocele. There are three types of Knobloch syndrome, which can be distinguished by the underlying genetic cause. Knobloch syndrome type I is caused by mutations in the COL18A1 gene. The genes associated with Knobloch syndrome type 2 and type 3 have not been identified; however, Knobloch syndrome type 3 has been linked to a specific region on chromosome 17, known as 17q11.2. Knobloch syndrome follows an autosomal recessive pattern of inheritance. Treatment is aimed at addressing the symptoms present in each individual and may include surgery to repair retinal detachments and occiptal encephaloceles.

KEGG : 36 Knobloch syndrome (KNO) is an autosomal recessive disorder characterized by the early onset of severe myopia, vitreoretinal degeneration with retinal detachment, and occipital encephalocele. Mutations in the COL18A1 gene were identified in KNO families.

Wikipedia : 74 Knobloch syndrome is a rare genetic disorder presenting severe eyesight problems and often a defect in... more...

Related Diseases for Knobloch Syndrome

Diseases in the Knobloch Syndrome family:

Knobloch Syndrome 1

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

(show all 41)
# Related Disease Score Top Affiliating Genes
1 knobloch syndrome 1 31.4 SLC19A1 COL18A1 ADAMTS18
2 vitreoretinal degeneration 11.1
3 myopia 10.6
4 retinal detachment 10.6
5 encephalocele 10.5
6 occipital encephalocele 10.3
7 autosomal recessive disease 10.3
8 pathologic nystagmus 10.2
9 retinal degeneration 10.1
10 polymicrogyria 10.1
11 polymicrogyria with or without vascular-type ehlers-danlos syndrome 10.0
12 isolated ectopia lentis 10.0
13 meningocele 10.0
14 cataract 10.0
15 albinism 10.0
16 vcan-related vitreoretinopathy 10.0
17 coloboma of macula 9.9
18 hypertelorism 9.9
19 telecanthus 9.9
20 albinism, oculocutaneous, type ia 9.9
21 choroidal dystrophy, central areolar, 1 9.9
22 persistent hyperplastic primary vitreous, autosomal recessive 9.9
23 retinoschisis 1, x-linked, juvenile 9.9
24 glaucoma-related pigment dispersion syndrome 9.9
25 myopia 10 9.9
26 leukemia, acute lymphoblastic 9.9
27 oculocutaneous albinism 9.9
28 ocular albinism 9.9
29 monocular esotropia 9.9
30 lens subluxation 9.9
31 alternating exotropia 9.9
32 exotropia 9.9
33 vitreous syneresis 9.9
34 epilepsy 9.9
35 eye disease 9.9
36 macular holes 9.9
37 vitreous detachment 9.9
38 esotropia 9.9
39 neuronal migration disorders 9.9
40 posttransplant acute limbic encephalitis 9.9
41 glaucoma, primary closed-angle 9.4 SLC19A1 COL18A1

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



Diseases related to Knobloch Syndrome

Symptoms & Phenotypes for Knobloch Syndrome

Human phenotypes related to Knobloch Syndrome:

31 (show all 24)
# Description HPO Frequency HPO Source Accession
1 myopia 31 hallmark (90%) HP:0000545
2 retinal detachment 31 hallmark (90%) HP:0000541
3 macular degeneration 31 hallmark (90%) HP:0000608
4 occipital encephalocele 31 hallmark (90%) HP:0002085
5 calvarial skull defect 31 hallmark (90%) HP:0001362
6 nystagmus 31 frequent (33%) HP:0000639
7 hydrocephalus 31 frequent (33%) HP:0000238
8 progressive visual loss 31 frequent (33%) HP:0000529
9 vitreoretinopathy 31 frequent (33%) HP:0007773
10 cataract 31 occasional (7.5%) HP:0000518
11 depressed nasal bridge 31 occasional (7.5%) HP:0005280
12 strabismus 31 occasional (7.5%) HP:0000486
13 epicanthus 31 occasional (7.5%) HP:0000286
14 ectopia lentis 31 occasional (7.5%) HP:0001083
15 patent ductus arteriosus 31 occasional (7.5%) HP:0001643
16 vesicoureteral reflux 31 occasional (7.5%) HP:0000076
17 joint hyperflexibility 31 occasional (7.5%) HP:0005692
18 pyloric stenosis 31 occasional (7.5%) HP:0002021
19 midface retrusion 31 occasional (7.5%) HP:0011800
20 dextrocardia 31 occasional (7.5%) HP:0001651
21 lymphangioma 31 occasional (7.5%) HP:0100764
22 bifid ureter 31 occasional (7.5%) HP:0030037
23 seizure 31 occasional (7.5%) HP:0001250
24 abnormal hair morphology 31 occasional (7.5%) HP:0001595

UMLS symptoms related to Knobloch Syndrome:


seizures, unspecified visual loss

MGI Mouse Phenotypes related to Knobloch Syndrome:

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

Search Clinical Trials , NIH Clinical Center for Knobloch Syndrome

Genetic Tests for Knobloch Syndrome

Anatomical Context for Knobloch Syndrome

MalaCards organs/tissues related to Knobloch Syndrome:

40
Eye, Retina, Skin

Publications for Knobloch Syndrome

Articles related to Knobloch Syndrome:

(show top 50) (show all 70)
# Title Authors PMID Year
1
CNS malformations in Knobloch syndrome with splice mutation in COL18A1 gene. 6 61 54
17546652 2007
2
Knobloch syndrome: novel mutations in COL18A1, evidence for genetic heterogeneity, and a functionally impaired polymorphism in endostatin. 61 54 6
14695535 2004
3
COL18A1 is a candidate eye iridocorneal angle-closure gene in humans. 6 61
30007336 2018
4
No evidence for locus heterogeneity in Knobloch syndrome. 6 61
23667181 2013
5
Collagen XVIII mutation in Knobloch syndrome with acute lymphoblastic leukemia. 61 6
20799329 2010
6
Locus heterogeneity and Knobloch syndrome. 6 61
20979194 2010
7
Mapping of a novel type III variant of Knobloch syndrome (KNO3) to chromosome 17q11.2. 6 61
17975799 2007
8
Molecular analysis of collagen XVIII reveals novel mutations, presence of a third isoform, and possible genetic heterogeneity in Knobloch syndrome. 6 61
12415512 2002
9
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 61
10942434 2000
10
The second report of Knobloch syndrome. 6 61
1554013 1992
11
Deep sequencing reveals 50 novel genes for recessive cognitive disorders. 6
21937992 2011
12
Homozygosity mapping through whole genome analysis identifies a COL18A1 mutation in an Indian family presenting with an autosomal recessive neurological disorder. 6
19160445 2009
13
Novel pathogenic mutations and skin biopsy analysis in Knobloch syndrome. 61 54
19390655 2009
14
A phenotypic variant of Knobloch syndrome. 61 54
18484314 2008
15
Physiological role of collagen XVIII and endostatin. 54 61
15857886 2005
16
Acute Angle Closure in Knobloch Syndrome. 61
33449584 2021
17
Variable phenotype of Knobloch syndrome due to biallelic COL18A1 mutations in children. 61
33238767 2020
18
Knobloch syndrome: a rare cause of paediatric retinal detachment. 61
33189607 2020
19
Knobloch syndrome in a patient from Chile. 61
32700429 2020
20
Unraveling the genetic cause of hereditary ophthalmic disorders in Arab societies from Israel and the Palestinian Authority. 61
31896775 2020
21
Macular Hole-Related Retinal Detachment in Children with Knobloch Syndrome. 61
32111543 2020
22
Three cases of molecularly confirmed Knobloch syndrome. 61
32178553 2020
23
Optical Coherence Tomography in Knobloch Syndrome. 61
31415705 2019
24
Retinal Detachment After Cyclophotocoagulation in a Child with Knobloch Syndrome. 61
30765955 2018
25
The distinct optic disk and peripapillary appearance in Donnai-Barrow syndrome. 61
29388841 2018
26
Knobloch syndrome caused by homozygous frameshift mutation of the COL18A1 gene in a Chinese pedigree. 61
29977801 2018
27
Knobloch syndrome associated with Polymicrogyria and early onset of retinal detachment: two case reports. 61
29178892 2017
28
Polymicrogyria and Intractable Epilepsy in Siblings With Knobloch Syndrome and Homozygous Mutation of COL18A1. 61
28950998 2017
29
Familial epilepsy with anterior polymicrogyria as a presentation of COL18A1 mutations. 61
28602933 2017
30
Progressive retinal degeneration in a girl with Knobloch syndrome who presented with signs of ocular albinism. 61
28144890 2017
31
Biometry, optical coherence tomography, and further clinical observations in Knobloch syndrome. 61
27088344 2017
32
Collagen XVIII in tissue homeostasis and dysregulation - Lessons learned from model organisms and human patients. 61
27746220 2017
33
Optical coherence tomography findings and successful repair of retina detachment in Knobloch syndrome. 61
28924418 2017
34
Molecular and Clinical Findings in Patients With Knobloch Syndrome. 61
27259167 2016
35
Lens subluxation and retinal dysfunction in a girl with homozygous VSX2 mutation. 61
24001013 2015
36
Brain malformations associated with Knobloch syndrome--review of literature, expanding clinical spectrum, and identification of novel mutations. 61
25456301 2014
37
Homozygosity mapping and whole exome sequencing reveal a novel homozygous COL18A1 mutation causing Knobloch syndrome. 61
25392994 2014
38
[Paediatric retinal detachment and hereditary vitreoretinal disorders]. 61
23986190 2013
39
Drosophila type XV/XVIII collagen mutants manifest integrin mediated mitochondrial dysfunction, which is improved by cyclosporin A and losartan. 61
23454281 2013
40
The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy. 61
23356391 2013
41
The distinct ophthalmic phenotype of Knobloch syndrome in children. 61
22399687 2012
42
Identification of ADAMTS18 as a gene mutated in Knobloch syndrome. 61
21862674 2011
43
The multiple functions of collagen XVIII in development and disease. 61
21163348 2011
44
Cataract surgery in Knobloch syndrome: a case report. 61
21691582 2011
45
Deletion of the basement membrane heparan sulfate proteoglycan type XVIII collagen causes hypertriglyceridemia in mice and humans. 61
21085708 2010
46
Characterization of drCol 15a1b: a novel component of the stem cell niche in the zebrafish retina. 61
20549708 2010
47
Functionally conserved cis-regulatory elements of COL18A1 identified through zebrafish transgenesis. 61
19895802 2010
48
Unexpected matrix diseases and novel therapeutic strategies. 61
19813027 2010
49
Knobloch syndrome: novel intra-oral findings. 61
18445000 2009
50
Syndromes, disorders and maternal risk factors associated with neural tube defects (V). 61
18935987 2008

Variations for Knobloch Syndrome

ClinVar genetic disease variations for Knobloch Syndrome:

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

Search GEO for disease gene expression data for Knobloch Syndrome.

Pathways for Knobloch Syndrome

Pathways related to Knobloch Syndrome 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

Cellular components related to Knobloch Syndrome 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 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

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
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