MCID: KNB006
MIFTS: 36

Knobloch Syndrome 1

Categories: Genetic diseases, Eye diseases, Fetal diseases, Rare diseases

Aliases & Classifications for Knobloch Syndrome 1

MalaCards integrated aliases for Knobloch Syndrome 1:

Name: Knobloch Syndrome 1 57 75 29 6
Knobloch Syndrome, Type 1 57 13 40
Retinal Detachment and Occipital Encephalocele 57 75
Knobloch Syndrome 59 73
Kno1 57 75
Kno 57 75
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
Inheritance:
autosomal recessive

Miscellaneous:
phenotypic variability


HPO:

32
knobloch syndrome 1:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 267750
Orphanet 59 ORPHA1571
UMLS via Orphanet 74 C1849409
ICD10 via Orphanet 34 Q15.8
MESH via Orphanet 45 C537209
MedGen 42 C1849409
UMLS 73 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. Affiliated tissues include eye, bone and skin, and related phenotypes are nystagmus and seizures

UniProtKB/Swiss-Prot : 75 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:

# Related Disease Score Top Affiliating Genes
1 knobloch syndrome 29.3 ADAMTS18 COL18A1 MIR6815 SLC19A1
2 encephalocele 12.6
3 occipital encephalocele 12.2
4 frontal encephalocele 12.2
5 basal encephalocele 12.2
6 parietal encephalocele 12.1
7 nasal encephalocele 12.1
8 isolated encephalocele 12.0
9 laryngeal atresia, encephalocele, and limb deformities 12.0
10 encephalocele anencephaly 11.8

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



Diseases related to Knobloch Syndrome 1

Symptoms & Phenotypes for Knobloch Syndrome 1

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
visual loss
phthisis bulbi
vitreoretinal degeneration
congenital cataract
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

Human phenotypes related to Knobloch Syndrome 1:

59 32 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 59 32 Frequent (79-30%) HP:0000639
2 seizures 59 32 Occasional (29-5%) HP:0001250
3 retinal detachment 59 32 Very frequent (99-80%) HP:0000541
4 visual loss 59 32 Frequent (79-30%) HP:0000572
5 vitreoretinal degeneration 59 32 Frequent (79-30%) HP:0000655
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 ectopia lentis 59 Occasional (29-5%)
19 vesicoureteral reflux 59 Occasional (29-5%)
20 macular degeneration 59 Very frequent (99-80%)
21 midface retrusion 59 Occasional (29-5%)
22 mental deterioration 32 occasional (7.5%) HP:0001268
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 skull defect 59 Very frequent (99-80%)
32 cerebral atrophy 32 HP:0002059
33 congenital cataract 32 HP:0000519
34 bifid ureter 59 Occasional (29-5%)
35 macular hypoplasia 32 HP:0001104
36 band keratopathy 32 HP:0000585
37 high myopia 32 HP:0011003

UMLS symptoms related to Knobloch Syndrome 1:


seizures, unspecified visual loss

Drugs & Therapeutics for Knobloch Syndrome 1

Search Clinical Trials , 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, Bone, Skin, Brain, Retina

Publications for Knobloch Syndrome 1

Articles related to Knobloch Syndrome 1:

(show all 31)
# Title Authors Year
1
Knobloch syndrome caused by homozygous frameshift mutation of the <i>COL18A1</i> gene in a Chinese pedigree. ( 29977801 )
2018
2
Polymicrogyria and Intractable Epilepsy in Siblings With Knobloch Syndrome and Homozygous Mutation of COL18A1. ( 28950998 )
2017
3
Optical coherence tomography findings and successful repair of retina detachment in Knobloch syndrome. ( 28924418 )
2017
4
Knobloch syndrome associated with Polymicrogyria and early onset of retinal detachment: two case reports. ( 29178892 )
2017
5
Progressive retinal degeneration in a girl with Knobloch syndrome who presented with signs of ocular albinism. ( 28144890 )
2017
6
Biometry, optical coherence tomography, and further clinical observations in Knobloch syndrome. ( 27088344 )
2016
7
Molecular and Clinical Findings in Patients With Knobloch Syndrome. ( 27259167 )
2016
8
Brain malformations associated with Knobloch syndrome--review of literature, expanding clinical spectrum, and identification of novel mutations. ( 25456301 )
2014
9
Homozygosity Mapping and Whole Exome Sequencing Reveal a Novel Homozygous COL18A1 Mutation Causing Knobloch Syndrome. ( 25392994 )
2014
10
No evidence for locus heterogeneity in Knobloch syndrome. ( 23667181 )
2013
11
The distinct ophthalmic phenotype of Knobloch syndrome in children. ( 22399687 )
2012
12
Cataract surgery in Knobloch syndrome: a case report. ( 21691582 )
2011
13
Identification of ADAMTS18 as a gene mutated in Knobloch syndrome. ( 21862674 )
2011
14
Locus heterogeneity and Knobloch syndrome. ( 20979194 )
2010
15
Collagen XVIII mutation in Knobloch syndrome with acute lymphoblastic leukemia. ( 20799329 )
2010
16
Knobloch syndrome: novel intra-oral findings. ( 18445000 )
2009
17
Novel pathogenic mutations and skin biopsy analysis in Knobloch syndrome. ( 19390655 )
2009
18
A phenotypic variant of Knobloch syndrome. ( 18484314 )
2008
19
CNS malformations in Knobloch syndrome with splice mutation in COL18A1 gene. ( 17546652 )
2007
20
Mapping of a novel type III variant of Knobloch syndrome (KNO3) to chromosome 17q11.2. ( 17975799 )
2007
21
How pathogenic is the p.D104N/endostatin polymorphic allele of COL18A1 in Knobloch syndrome? ( 15714516 )
2005
22
Knobloch syndrome: novel mutations in COL18A1, evidence for genetic heterogeneity, and a functionally impaired polymorphism in endostatin. ( 14695535 )
2004
23
Persistence of fetal vasculature in a patient with Knobloch syndrome: potential role for endostatin in fetal vascular remodeling of the eye. ( 15465551 )
2004
24
Evidence of neuronal migration disorders in Knobloch syndrome: clinical and molecular analysis of two novel families. ( 12707952 )
2003
25
Molecular analysis of collagen XVIII reveals novel mutations, presence of a third isoform, and possible genetic heterogeneity in Knobloch syndrome. ( 12415512 )
2002
26
Knobloch syndrome involving midline scalp defect of the frontal region. ( 10607954 )
2000
27
Report of two sibs with Knobloch syndrome (encephalocoele and viteroretinal degeneration) and other anomalies. ( 9677068 )
1998
28
A gene which causes severe ocular alterations and occipital encephalocele (Knobloch syndrome) is mapped to 21q22.3. ( 8776601 )
1996
29
Knobloch syndrome in a large Brazilian consanguineous family: confirmation of autosomal recessive inheritance. ( 7802003 )
1994
30
Congenital scalp defects and vitreoretinal degeneration: redefining the Knobloch syndrome. ( 8484411 )
1993
31
The second report of Knobloch syndrome. ( 1554013 )
1992

Variations for Knobloch Syndrome 1

ClinVar genetic disease variations for Knobloch Syndrome 1:

6
(show top 50) (show all 287)
# Gene Variation Type Significance SNP ID Assembly Location
1 COL18A1 COL18A1, IVS1, A-T, -2 single nucleotide variant Pathogenic
2 COL18A1 COL18A1, 2-BP DEL, 3514CT deletion Pathogenic
3 COL18A1 NM_030582.3(COL18A1): c.3363dupC (p.Gly1122Argfs) duplication Pathogenic rs886037627 GRCh37 Chromosome 21, 46924425: 46924425
4 COL18A1 NM_030582.3(COL18A1): c.3363dupC (p.Gly1122Argfs) duplication Pathogenic rs886037627 GRCh38 Chromosome 21, 45504511: 45504511
5 COL18A1 COL18A1, IVS36DS, A-C, +3 single nucleotide variant Pathogenic
6 COL18A1 COL18A1, 2-BP DEL, 3617CT deletion Pathogenic
7 COL18A1 COL18A1, 2-BP DEL deletion Pathogenic
8 COL18A1 NM_130445.3(COL18A1): c.3514_3515delCT (p.Leu1172Valfs) deletion Pathogenic rs398122391 GRCh37 Chromosome 21, 46930005: 46930006
9 COL18A1 NM_130445.3(COL18A1): c.3514_3515delCT (p.Leu1172Valfs) deletion Pathogenic rs398122391 GRCh38 Chromosome 21, 45510091: 45510092
10 COL18A1 NM_130445.2(COL18A1): c.2118dupC (p.Gly707Argfs) duplication Pathogenic rs797045476 GRCh37 Chromosome 21, 46911189: 46911189
11 COL18A1 NM_130445.2(COL18A1): c.2118dupC (p.Gly707Argfs) duplication Pathogenic rs797045476 GRCh38 Chromosome 21, 45491275: 45491275
12 COL18A1 NM_130445.3(COL18A1): c.241C> T (p.Arg81Trp) single nucleotide variant Likely benign rs76658745 GRCh37 Chromosome 21, 46888290: 46888290
13 COL18A1 NM_130445.3(COL18A1): c.241C> T (p.Arg81Trp) single nucleotide variant Likely benign rs76658745 GRCh38 Chromosome 21, 45468376: 45468376
14 COL18A1 NM_030582.3(COL18A1): c.1377C> G (p.Pro459=) single nucleotide variant Benign rs2230687 GRCh37 Chromosome 21, 46896303: 46896303
15 COL18A1 NM_030582.3(COL18A1): c.1377C> G (p.Pro459=) single nucleotide variant Benign rs2230687 GRCh38 Chromosome 21, 45476389: 45476389
16 COL18A1 NM_030582.3(COL18A1): c.1386G> T (p.Thr462=) single nucleotide variant Benign rs2230688 GRCh37 Chromosome 21, 46896312: 46896312
17 COL18A1 NM_030582.3(COL18A1): c.1386G> T (p.Thr462=) single nucleotide variant Benign rs2230688 GRCh38 Chromosome 21, 45476398: 45476398
18 COL18A1 NM_030582.3(COL18A1): c.1455G> T (p.Val485=) single nucleotide variant Likely benign rs17338853 GRCh38 Chromosome 21, 45476467: 45476467
19 COL18A1 NM_030582.3(COL18A1): c.1455G> T (p.Val485=) single nucleotide variant Likely benign rs17338853 GRCh37 Chromosome 21, 46896381: 46896381
20 COL18A1 NM_030582.3(COL18A1): c.1683G> A (p.Ala561=) single nucleotide variant Likely benign rs2230689 GRCh37 Chromosome 21, 46897801: 46897801
21 COL18A1 NM_030582.3(COL18A1): c.1683G> A (p.Ala561=) single nucleotide variant Likely benign rs2230689 GRCh38 Chromosome 21, 45477887: 45477887
22 COL18A1 NM_030582.3(COL18A1): c.2215-6G> A single nucleotide variant Uncertain significance rs142726108 GRCh37 Chromosome 21, 46902703: 46902703
23 COL18A1 NM_030582.3(COL18A1): c.2215-6G> A single nucleotide variant Uncertain significance rs142726108 GRCh38 Chromosome 21, 45482789: 45482789
24 COL18A1 NM_030582.3(COL18A1): c.2460T> C (p.Leu820=) single nucleotide variant Benign rs11702425 GRCh37 Chromosome 21, 46908355: 46908355
25 COL18A1 NM_030582.3(COL18A1): c.2460T> C (p.Leu820=) single nucleotide variant Benign rs11702425 GRCh38 Chromosome 21, 45488441: 45488441
26 COL18A1 NM_030582.3(COL18A1): c.2490G> A (p.Pro830=) single nucleotide variant Likely benign rs61731167 GRCh37 Chromosome 21, 46909426: 46909426
27 COL18A1 NM_030582.3(COL18A1): c.2490G> A (p.Pro830=) single nucleotide variant Likely benign rs61731167 GRCh38 Chromosome 21, 45489512: 45489512
28 COL18A1 NM_030582.3(COL18A1): c.2521G> A (p.Val841Ile) single nucleotide variant Benign rs62000962 GRCh37 Chromosome 21, 46910210: 46910210
29 COL18A1 NM_030582.3(COL18A1): c.2521G> A (p.Val841Ile) single nucleotide variant Benign rs62000962 GRCh38 Chromosome 21, 45490296: 45490296
30 COL18A1 NM_030582.3(COL18A1): c.2657C> G (p.Pro886Arg) single nucleotide variant Likely benign rs79980197 GRCh37 Chromosome 21, 46911188: 46911188
31 COL18A1 NM_030582.3(COL18A1): c.2657C> G (p.Pro886Arg) single nucleotide variant Likely benign rs79980197 GRCh38 Chromosome 21, 45491274: 45491274
32 COL18A1 NM_030582.3(COL18A1): c.2736G> A (p.Pro912=) single nucleotide variant Likely benign rs115470104 GRCh38 Chromosome 21, 45492695: 45492695
33 COL18A1 NM_030582.3(COL18A1): c.2736G> A (p.Pro912=) single nucleotide variant Likely benign rs115470104 GRCh37 Chromosome 21, 46912609: 46912609
34 COL18A1 NM_030582.3(COL18A1): c.3268-8G> A single nucleotide variant Likely benign rs116618591 GRCh37 Chromosome 21, 46924322: 46924322
35 COL18A1 NM_030582.3(COL18A1): c.3268-8G> A single nucleotide variant Likely benign rs116618591 GRCh38 Chromosome 21, 45504408: 45504408
36 COL18A1 NM_030582.3(COL18A1): c.3321C> T (p.Pro1107=) single nucleotide variant Likely benign rs11544970 GRCh38 Chromosome 21, 45504469: 45504469
37 COL18A1 NM_030582.3(COL18A1): c.3321C> T (p.Pro1107=) single nucleotide variant Likely benign rs11544970 GRCh37 Chromosome 21, 46924383: 46924383
38 COL18A1 NM_030582.3(COL18A1): c.3762A> G (p.Thr1254=) single nucleotide variant Benign rs12483761 GRCh37 Chromosome 21, 46927489: 46927489
39 COL18A1 NM_030582.3(COL18A1): c.3762A> G (p.Thr1254=) single nucleotide variant Benign rs12483761 GRCh38 Chromosome 21, 45507575: 45507575
40 COL18A1 NM_030582.3(COL18A1): c.3978G> A (p.Ala1326=) single nucleotide variant Benign rs1050351 GRCh38 Chromosome 21, 45509553: 45509553
41 COL18A1 NM_030582.3(COL18A1): c.3978G> A (p.Ala1326=) single nucleotide variant Benign rs1050351 GRCh37 Chromosome 21, 46929467: 46929467
42 COL18A1 NM_030582.3(COL18A1): c.*16G> A single nucleotide variant Benign rs7499 GRCh37 Chromosome 21, 46932328: 46932328
43 COL18A1 NM_030582.3(COL18A1): c.*16G> A single nucleotide variant Benign rs7499 GRCh38 Chromosome 21, 45512414: 45512414
44 COL18A1 NM_130445.3(COL18A1): c.2056delC (p.Arg686Glyfs) deletion Pathogenic rs886043809 GRCh37 Chromosome 21, 46910774: 46910774
45 COL18A1 NM_130445.3(COL18A1): c.2056delC (p.Arg686Glyfs) deletion Pathogenic rs886043809 GRCh38 Chromosome 21, 45490860: 45490860
46 COL18A1 NM_130445.3(COL18A1): c.126G> A (p.Val42=) single nucleotide variant Likely benign rs115800039 GRCh38 Chromosome 21, 45468261: 45468261
47 COL18A1 NM_130445.3(COL18A1): c.126G> A (p.Val42=) single nucleotide variant Likely benign rs115800039 GRCh37 Chromosome 21, 46888175: 46888175
48 COL18A1 NM_130445.3(COL18A1): c.217G> A (p.Asp73Asn) single nucleotide variant Uncertain significance rs370054491 GRCh38 Chromosome 21, 45468352: 45468352
49 COL18A1 NM_130445.3(COL18A1): c.217G> A (p.Asp73Asn) single nucleotide variant Uncertain significance rs370054491 GRCh37 Chromosome 21, 46888266: 46888266
50 COL18A1 NM_130445.3(COL18A1): c.603C> T (p.Ala201=) single nucleotide variant Likely benign rs17004776 GRCh37 Chromosome 21, 46888652: 46888652

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 ADAMTS18 COL18A1

GO Terms for Knobloch Syndrome 1

Sources for Knobloch Syndrome 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
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38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
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49 NCI
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54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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