KNO1
MCID: KNB006
MIFTS: 46

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 56 73 29 6
Knobloch Syndrome, Type 1 56 13 39
Retinal Detachment and Occipital Encephalocele 56 73
Knobloch Syndrome 58 71
Kno1 56 73
Kno 56 73
Retinal Detachment-Occipital Encephalocele Syndrome 58
Knobloch-Layer Syndrome 58
Encephalocele 43

Characteristics:

Orphanet epidemiological data:

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

OMIM:

56
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 56 267750
MESH via Orphanet 44 C537209
ICD10 via Orphanet 33 Q15.8
UMLS via Orphanet 72 C1849409
Orphanet 58 ORPHA1571
UMLS 71 C1849409

Summaries for Knobloch Syndrome 1

OMIM : 56 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 drugs leucovorin and Folic acid have been mentioned in the context of this disorder. Affiliated tissues include eye, bone and spinal cord, 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 370)
# Related Disease Score Top Affiliating Genes
1 knobloch syndrome 30.5 SLC19A1 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 dandy-walker syndrome 11.6
16 meckel syndrome, type 3 11.5
17 hydrocephalus 11.5
18 neural tube defects 11.5
19 nasal glial heterotopia 11.4
20 chiari malformation 11.4
21 frontonasal dysplasia 1 11.4
22 constricting bands, congenital 11.4
23 vitreoretinal degeneration 11.3
24 boomerang dysplasia 11.2
25 oculoauriculofrontonasal syndrome 11.2
26 meckel syndrome, type 4 11.2
27 meckel syndrome, type 8 11.2
28 meckel syndrome, type 9 11.2
29 craniotelencephalic dysplasia 11.1
30 dyssegmental dysplasia, silverman-handmaker type 11.1
31 frontofacionasal dysplasia 11.1
32 orofaciodigital syndrome iv 11.1
33 meckel syndrome, type 7 11.1
34 roberts syndrome 11.1
35 otopalatodigital syndrome, type ii 11.1
36 meckel syndrome, type 2 11.1
37 meckel syndrome, type 5 11.1
38 meckel syndrome, type 6 11.1
39 meckel syndrome, type 10 11.1
40 craniofacial anomalies and anterior segment dysgenesis syndrome 11.1
41 meckel syndrome, type 11 11.1
42 meckel syndrome 12 11.1
43 meckel syndrome 13 11.1
44 midface dysplasia 11.1
45 acrofrontofacionasal dysostosis 11.1
46 schisis association 11.1
47 cranial meningocele 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:

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 cataract 58 Occasional (29-5%)
7 depressed nasal bridge 58 Occasional (29-5%)
8 seizures 58 Occasional (29-5%)
9 hydrocephalus 58 Frequent (79-30%)
10 ataxia 31 HP:0001251
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 abnormality of the vitreous humor 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 seizure 31 HP:0001250
41 peripapillary atrophy 31 HP:0500087

Symptoms via clinical synopsis from OMIM:

56
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

UMLS symptoms related to Knobloch Syndrome 1:


seizures, unspecified visual loss

MGI Mouse Phenotypes related to Knobloch Syndrome 1:

45
# 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

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

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
leucovorin Approved 58-05-9 6006 143
2
Folic acid Approved, Nutraceutical, Vet_approved 59-30-3 6037
3 Liver Extracts
4 Vitamins
5 Vitamin B Complex
6 Folate
7 Vitamin B9

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 Completed NCT00068224
3 A Prospective Longitudinal Quality of Life Study in Patients Undergoing Endoscopic Endonasal Skull Base Surgery Recruiting NCT04087902
4 Knowledge and Follow-up of Vitamin B9 Supplementation Recommendations for Women in the Periconceptional Period to Prevent Neural Tube Closure Defects: a Study Conducted With Health Professionnals and Women Who Have Just Given Birth in Rennes CHU. Recruiting NCT04195542
5 Sunnaas International Network Pediatric Spinal Cord Injury Study - an International Multicenterstudy in Seven Countries Recruiting NCT04117854

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, Spinal Cord, Kidney, Liver, 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. 56 6
30007336 2018
2
No evidence for locus heterogeneity in Knobloch syndrome. 6 56
23667181 2013
3
Deep sequencing reveals 50 novel genes for recessive cognitive disorders. 6 56
21937992 2011
4
Identification of ADAMTS18 as a gene mutated in Knobloch syndrome. 6 56
21862674 2011
5
Collagen XVIII mutation in Knobloch syndrome with acute lymphoblastic leukemia. 56 6
20799329 2010
6
Locus heterogeneity and Knobloch syndrome. 6 56
20979194 2010
7
Homozygosity mapping through whole genome analysis identifies a COL18A1 mutation in an Indian family presenting with an autosomal recessive neurological disorder. 6 56
19160445 2009
8
Mapping of a novel type III variant of Knobloch syndrome (KNO3) to chromosome 17q11.2. 6 56
17975799 2007
9
CNS malformations in Knobloch syndrome with splice mutation in COL18A1 gene. 56 6
17546652 2007
10
Knobloch syndrome: novel mutations in COL18A1, evidence for genetic heterogeneity, and a functionally impaired polymorphism in endostatin. 6 56
14695535 2004
11
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 56
10942434 2000
12
The second report of Knobloch syndrome. 6 56
1554013 1992
13
Molecular and Clinical Findings in Patients With Knobloch Syndrome. 56
27259167 2016
14
Brain malformations associated with Knobloch syndrome--review of literature, expanding clinical spectrum, and identification of novel mutations. 56
25456301 2014
15
Evidence of neuronal migration disorders in Knobloch syndrome: clinical and molecular analysis of two novel families. 56
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. 56
10607954 2000
18
Report of two sibs with Knobloch syndrome (encephalocoele and viteroretinal degeneration) and other anomalies. 56
9677068 1998
19
A gene which causes severe ocular alterations and occipital encephalocele (Knobloch syndrome) is mapped to 21q22.3. 56
8776601 1996
20
Knobloch syndrome in a large Brazilian consanguineous family: confirmation of autosomal recessive inheritance. 56
7802003 1994
21
Congenital scalp defects and vitreoretinal degeneration: redefining the Knobloch syndrome. 56
8484411 1993
22
Syndromes with cephaloceles. 56
7101196 1982
23
Hydrocephalus, agyria, retinal dysplasia, encephalocele (HARD +/- E) syndrome: an autosomal recessive condition. 56
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 242) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 COL18A1 NM_030582.4(COL18A1):c.3213dup (p.Gly1072fs)duplication Pathogenic 403722 rs749009747 21:46917558-46917559 21:45497644-45497645
2 COL18A1 NM_030582.4(COL18A1):c.1610dup (p.Gly538fs)duplication Pathogenic 548656 rs1555860555 21:46897722-46897723 21:45477808-45477809
3 COL18A1 NM_030582.4(COL18A1):c.4490_4491insTGCC (p.Cys1498fs)insertion Pathogenic 548657 rs1555877107 21:46932251-46932252 21:45512337-45512338
4 COL18A1 NM_030582.4(COL18A1):c.4349+2T>CSNV Pathogenic 623178 rs113847452 21:46931142-46931142 21:45511228-45511228
5 COL18A1 NM_030582.4(COL18A1):c.3509_3518del (p.Pro1170fs)deletion Pathogenic 623349 rs756797124 21:46925150-46925159 21:45505236-45505245
6 COL18A1 NM_030582.4(COL18A1):c.969dup (p.Ala324fs)duplication Pathogenic 812292 21:46888477-46888478 21:45468563-45468564
7 COL18A1 NM_030582.4(COL18A1):c.808del (p.Arg270fs)deletion Pathogenic 872909
8 COL18A1 NM_030582.4(COL18A1):c.1129del (p.Leu377fs)deletion Pathogenic 872910
9 COL18A1 , SLC19A1 NM_030582.4(COL18A1):c.4053_4054del (p.Leu1352fs)deletion Pathogenic 684620 21:46930001-46930002 21:45510087-45510088
10 COL18A1 COL18A1, IVS1AS, A-T, -2SNV Pathogenic 17115
11 COL18A1 COL18A1, 2-BP DEL, 3514CTdeletion Pathogenic 17116
12 COL18A1 NM_030582.4(COL18A1):c.3363dup (p.Gly1122fs)duplication Pathogenic 17117 rs769882681 21:46924418-46924419 21:45504504-45504505
13 COL18A1 COL18A1, IVS36DS, A-C, +3SNV Pathogenic 17119
14 COL18A1 COL18A1, 2-BP DEL, 3617CTdeletion Pathogenic 29652
15 COL18A1 COL18A1, 2-BP DELdeletion Pathogenic 29653
16 COL18A1 NM_030582.4(COL18A1):c.4054_4055del (p.Leu1352fs)deletion Pathogenic 65410 rs398122391 21:46930005-46930006 21:45510091-45510092
17 COL18A1 NM_130445.2(COL18A1):c.2118dupC (p.Gly707Argfs)duplication Pathogenic 65411 rs775168204 21:46911182-46911183 21:45491268-45491269
18 COL18A1 NM_030582.4(COL18A1):c.1698del (p.Gly567fs)deletion Pathogenic 915433 21:46897813-46897813 21:45477899-45477899
19 COL18A1 NM_030582.4(COL18A1):c.2416C>T (p.Arg806Ter)SNV Likely pathogenic 915432 21:46907403-46907403 21:45487489-45487489
20 COL18A1 NM_030582.4(COL18A1):c.4355_4356TG[1] (p.Trp1453fs)short repeat Likely pathogenic 800861 21:46932115-46932116 21:45512201-45512202
21 COL18A1 NM_030582.4(COL18A1):c.3772C>T (p.Arg1258Ter)SNV Likely pathogenic 666965 21:46927499-46927499 21:45507585-45507585
22 COL18A1 NM_030582.4(COL18A1):c.2153G>T (p.Gly718Val)SNV Likely pathogenic 427899 rs1114167359 21:46901878-46901878 21:45481964-45481964
23 COL18A1 NM_030582.4(COL18A1):c.2698-9C>TSNV Conflicting interpretations of pathogenicity 447118 rs200143450 21:46912440-46912440 21:45492526-45492526
24 COL18A1 NM_030582.4(COL18A1):c.2445C>T (p.Pro815=)SNV Conflicting interpretations of pathogenicity 770010 21:46908340-46908340 21:45488426-45488426
25 COL18A1 NM_030582.4(COL18A1):c.1993-6G>ASNV Conflicting interpretations of pathogenicity 340222 rs200886865 21:46900608-46900608 21:45480694-45480694
26 COL18A1 NM_030582.4(COL18A1):c.2571+9C>TSNV Uncertain significance 340232 rs780751282 21:46910269-46910269 21:45490355-45490355
27 COL18A1 NM_030582.4(COL18A1):c.2625C>T (p.Asp875=)SNV Uncertain significance 340236 rs373006940 21:46911156-46911156 21:45491242-45491242
28 COL18A1 NM_030582.4(COL18A1):c.2688G>A (p.Ser896=)SNV Uncertain significance 340237 rs374522196 21:46911219-46911219 21:45491305-45491305
29 COL18A1 NM_030582.4(COL18A1):c.1153G>A (p.Val385Met)SNV Uncertain significance 340197 rs201116208 21:46888662-46888662 21:45468748-45468748
30 COL18A1 NM_030582.4(COL18A1):c.*30G>ASNV Uncertain significance 340275 rs373537387 21:46932342-46932342 21:45512428-45512428
31 COL18A1 NM_030582.4(COL18A1):c.2920-15C>TSNV Uncertain significance 340244 rs754575228 21:46914761-46914761 21:45494847-45494847
32 COL18A1 NM_030582.4(COL18A1):c.2969G>A (p.Arg990Gln)SNV Uncertain significance 340245 rs751578852 21:46914825-46914825 21:45494911-45494911
33 COL18A1 NM_030582.4(COL18A1):c.3117+9C>TSNV Uncertain significance 340248 rs774784084 21:46916491-46916491 21:45496577-45496577
34 COL18A1 NM_030582.4(COL18A1):c.3172C>T (p.Pro1058Ser)SNV Uncertain significance 340252 rs377290522 21:46917524-46917524 21:45497610-45497610
35 COL18A1 NM_030582.4(COL18A1):c.3223+11C>GSNV Uncertain significance 340253 rs886057128 21:46917586-46917586 21:45497672-45497672
36 COL18A1 NM_030582.4(COL18A1):c.3328G>A (p.Gly1110Ser)SNV Uncertain significance 340257 rs771054336 21:46924390-46924390 21:45504476-45504476
37 COL18A1 NM_194255.4(SLC19A1):c.*2409G>ASNV Uncertain significance 340295 rs886057145 21:46933163-46933163 21:45513249-45513249
38 COL18A1 NM_194255.4(SLC19A1):c.*2172G>ASNV Uncertain significance 340299 rs756987643 21:46933400-46933400 21:45513486-45513486
39 COL18A1 NM_194255.4(SLC19A1):c.*2103G>CSNV Uncertain significance 340302 rs527507454 21:46933469-46933469 21:45513555-45513555
40 COL18A1 NM_194255.4(SLC19A1):c.*2057T>CSNV Uncertain significance 340303 rs886057147 21:46933515-46933515 21:45513601-45513601
41 COL18A1 NM_194255.4(SLC19A1):c.*2918G>CSNV Uncertain significance 340284 rs886057139 21:46932654-46932654 21:45512740-45512740
42 COL18A1 NM_194255.4(SLC19A1):c.*2891G>ASNV Uncertain significance 340285 rs886057140 21:46932681-46932681 21:45512767-45512767
43 COL18A1 NM_194255.4(SLC19A1):c.*2776G>ASNV Uncertain significance 340287 rs548084117 21:46932796-46932796 21:45512882-45512882
44 COL18A1 NM_194255.4(SLC19A1):c.*2676G>TSNV Uncertain significance 340292 rs886057143 21:46932896-46932896 21:45512982-45512982
45 COL18A1 NM_030582.4(COL18A1):c.1584G>A (p.Pro528=)SNV Uncertain significance 340211 rs886057122 21:46897702-46897702 21:45477788-45477788
46 COL18A1 NM_030582.4(COL18A1):c.2754+15G>ASNV Uncertain significance 896624 21:46912642-46912642 21:45492728-45492728
47 COL18A1 NM_030582.4(COL18A1):c.2974-4C>GSNV Uncertain significance 898259 21:46915268-46915268 21:45495354-45495354
48 COL18A1 NM_030582.4(COL18A1):c.3268-12T>CSNV Uncertain significance 895261 21:46924318-46924318 21:45504404-45504404
49 ADAMTS18 NM_199355.4(ADAMTS18):c.536C>T (p.Ser179Leu)SNV Uncertain significance 30670 rs387906972 16:77401580-77401580 16:77367683-77367683
50 COL18A1 NM_030582.4(COL18A1):c.757G>A (p.Asp253Asn)SNV Uncertain significance 340192 rs370054491 21:46888266-46888266 21:45468352-45468352

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
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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