MCID: BRT029
MIFTS: 50

Brittle Cornea Syndrome 2

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

Aliases & Classifications for Brittle Cornea Syndrome 2

MalaCards integrated aliases for Brittle Cornea Syndrome 2:

Name: Brittle Cornea Syndrome 2 53 12 71 28 13 69
Brittle Cornea Syndrome 12 49 55 36 13 14
Ehlers-Danlos Syndrome Type 6 41 69
Bcs2 53 71
Corneal Fragility, Keratoglobus, Blue Sclerae, Joint Hyperextensibility 49
Fragilitas Oculi with Joint Hyperextensibility 49
Dysgenesis Mesodermalis Corneae Et Sclerae 49
Type Vib Ehlers-Danlos Syndrome 12
Ehlers-Danlos Syndrome 6b 69
Kyphoscoliosis Type 12
Kyphoscoliosis 28

Characteristics:

Orphanet epidemiological data:

55
brittle cornea syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
heterozygous carriers have blue sclerae, small joint hypermobility, and mild thinning of cornea


HPO:

31
brittle cornea syndrome 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Brittle Cornea Syndrome 2

NIH Rare Diseases : 49 Brittle cornea syndrome (BCS) is a type of connective tissue disorder that mainly affects the eyes, joints and skin. Signs and symptoms may include rupture of the cornea after only minor trauma; degeneration of the cornea (keratoconus) or thinning and protrusion of the cornea (keratoglobus); bluish tint in the white part of the eyes (blue sclerae); hypermobile joints; hyperelastic skin; hearing defects; and dental abnormalities. There are 2 types of BCS which are distinguished by the mutated gene that causes the condition. BCS type 1 is caused by mutations in the ZNF469 gene and BCS type 2 is caused by mutations in the PRDM5 gene. BCS is inherited in an autosomal recessive manner. Last updated: 2/17/2012

MalaCards based summary : Brittle Cornea Syndrome 2, also known as brittle cornea syndrome, is related to ehlers-danlos syndrome and keratoconus, and has symptoms including myalgia, abnormality of epiphysis morphology and gait disturbance. An important gene associated with Brittle Cornea Syndrome 2 is PRDM5 (PR/SET Domain 5), and among its related pathways/superpathways are Integrin Pathway and Phospholipase-C Pathway. The drugs Aromatase Inhibitors and Estrogen Antagonists have been mentioned in the context of this disorder. Affiliated tissues include skin, eye and breast.

UniProtKB/Swiss-Prot : 71 Brittle cornea syndrome 2: A disorder characterized by extreme corneal thinning resulting in corneal rupture after minor trauma, blue sclerae, keratoconus or keratoglobus, hyperelasticity of the skin, and hypermobile joints.

Description from OMIM: 614170

Related Diseases for Brittle Cornea Syndrome 2

Graphical network of the top 20 diseases related to Brittle Cornea Syndrome 2:



Diseases related to Brittle Cornea Syndrome 2

Symptoms & Phenotypes for Brittle Cornea Syndrome 2

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Eyes:
myopia
blue sclerae
keratoconus
keratoglobus
sclerocornea (in some patients)
more
Abdomen External Features:
hernia, inguinal, umbilical, or epigastric (in some patients)

Skeletal Pelvis:
developmental dysplasia of the hip (in some patients)

Muscle Soft Tissue:
myalgia (in some patients)

Head And Neck Ears:
hearing loss, sensorineural and conductive
hypercompliant tympanic membranes

Skeletal:
small joint hypermobility
abnormal gait (in some patients)
increased fractures (in some patients)

Skin Nails Hair Skin:
soft with easy bruising (in some patients)
poor healing with abnormal scarring (in some patients)
hyperelasticity (in some patients)


Clinical features from OMIM:

614170

Human phenotypes related to Brittle Cornea Syndrome 2:

55 31 (show all 44)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 myalgia 55 31 occasional (7.5%) Frequent (79-30%) HP:0003326
2 abnormality of epiphysis morphology 55 31 occasional (7.5%) Occasional (29-5%) HP:0005930
3 gait disturbance 55 31 occasional (7.5%) Frequent (79-30%) HP:0001288
4 scoliosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0002650
5 hip dysplasia 55 31 occasional (7.5%) Occasional (29-5%) HP:0001385
6 abnormality of the dentition 55 31 occasional (7.5%) Occasional (29-5%) HP:0000164
7 pes planus 55 31 occasional (7.5%) Occasional (29-5%) HP:0001763
8 sensorineural hearing impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000407
9 neonatal hypotonia 55 31 occasional (7.5%) Occasional (29-5%) HP:0001319
10 osteoporosis 55 31 frequent (33%) Frequent (79-30%) HP:0000939
11 cleft palate 55 31 occasional (7.5%) Occasional (29-5%) HP:0000175
12 hernia 55 31 occasional (7.5%) Occasional (29-5%) HP:0100790
13 joint hyperflexibility 55 31 frequent (33%) Frequent (79-30%) HP:0005692
14 corneal dystrophy 55 31 hallmark (90%) Very frequent (99-80%) HP:0001131
15 corneal erosion 55 31 occasional (7.5%) Occasional (29-5%) HP:0200020
16 glaucoma 55 31 occasional (7.5%) Occasional (29-5%) HP:0000501
17 retinal detachment 55 31 occasional (7.5%) Occasional (29-5%) HP:0000541
18 visual loss 55 31 frequent (33%) Frequent (79-30%) HP:0000572
19 arachnodactyly 55 31 occasional (7.5%) Occasional (29-5%) HP:0001166
20 mitral valve prolapse 55 31 occasional (7.5%) Occasional (29-5%) HP:0001634
21 conductive hearing impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000405
22 bruising susceptibility 55 31 frequent (33%) Frequent (79-30%) HP:0000978
23 pulmonic stenosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0001642
24 hallux valgus 55 31 occasional (7.5%) Occasional (29-5%) HP:0001822
25 blue sclerae 55 31 frequent (33%) Frequent (79-30%) HP:0000592
26 hyperextensible skin 55 31 hallmark (90%) Very frequent (99-80%) HP:0000974
27 keratoglobus 55 31 hallmark (90%) Very frequent (99-80%) HP:0001119
28 increased susceptibility to fractures 55 31 occasional (7.5%) Occasional (29-5%) HP:0002659
29 camptodactyly 55 31 occasional (7.5%) Occasional (29-5%) HP:0012385
30 soft skin 55 31 hallmark (90%) Very frequent (99-80%) HP:0000977
31 corneal scarring 55 31 frequent (33%) Frequent (79-30%) HP:0000559
32 abnormality of hair pigmentation 55 31 frequent (33%) Frequent (79-30%) HP:0009887
33 inguinal hernia 31 occasional (7.5%) HP:0000023
34 hearing impairment 31 HP:0000365
35 umbilical hernia 31 occasional (7.5%) HP:0001537
36 megalocornea 31 occasional (7.5%) HP:0000485
37 myopia 31 HP:0000545
38 flat cornea 31 occasional (7.5%) HP:0007720
39 recurrent fractures 31 occasional (7.5%) HP:0002757
40 sclerocornea 31 occasional (7.5%) HP:0000647
41 keratoconus 31 HP:0000563
42 severe myopia 55 Very frequent (99-80%)
43 decreased corneal thickness 55 Very frequent (99-80%)
44 high myopia 31 hallmark (90%) HP:0011003

UMLS symptoms related to Brittle Cornea Syndrome 2:


unspecified visual loss

Drugs & Therapeutics for Brittle Cornea Syndrome 2

Drugs for Brittle Cornea Syndrome 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Aromatase Inhibitors
2 Estrogen Antagonists
3 Estrogens
4 Hormone Antagonists
5 Hormones
6 Hormones, Hormone Substitutes, and Hormone Antagonists
7 Steroid Synthesis Inhibitors

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 How Breast Conservative Surgery (BCS) Affects Women's Daily Activities On Post-Operation 2 Days? Unknown status NCT00265213
2 Current Practice Pattern and Effect of Training in Upper Endoscopic Biopsy Completed NCT02044536
3 Exercise to Prevent Aromatase Inhibitor Side Effects in Breast Cancer Patients Terminated NCT01954706

Search NIH Clinical Center for Brittle Cornea Syndrome 2

Cochrane evidence based reviews: ehlers-danlos syndrome type 6

Genetic Tests for Brittle Cornea Syndrome 2

Genetic tests related to Brittle Cornea Syndrome 2:

# Genetic test Affiliating Genes
1 Brittle Cornea Syndrome 2 28 PRDM5
2 Kyphoscoliosis 28

Anatomical Context for Brittle Cornea Syndrome 2

MalaCards organs/tissues related to Brittle Cornea Syndrome 2:

38
Skin, Eye, Breast, Bone

Publications for Brittle Cornea Syndrome 2

Articles related to Brittle Cornea Syndrome 2:

(show all 21)
# Title Authors Year
1
Identification of Mutations in the PRDM5 Gene in Brittle Cornea Syndrome. ( 27032025 )
2016
2
Brittle Cornea Syndrome: Case Report with Novel Mutation in the PRDM5 Gene and Review of the Literature. ( 26221552 )
2015
3
Corneal Cross-Linking for Brittle Cornea Syndrome. ( 26266434 )
2015
4
Brittle cornea syndrome ZNF469 mutation carrier phenotype and segregation analysis of rare ZNF469 variants in familial keratoconus. ( 25564447 )
2015
5
Brittle cornea syndrome: a case report and comparison with Ehlers Danlos syndrome. ( 25727605 )
2015
6
Bruch's membrane abnormalities in PRDM5-related brittle cornea syndrome. ( 26560304 )
2015
7
A role for repressive complexes and H3K9 di-methylation in PRDM5-associated brittle cornea syndrome. ( 26395458 )
2015
8
Brittle cornea syndrome: a case report and comparison with Ehlers Danlos syndrome. ( 25266838 )
2014
9
Brittle cornea syndrome: recognition, molecular diagnosis and management. ( 23642083 )
2013
10
ZNF469 frequently mutated in the brittle cornea syndrome (BCS) is a single exon gene possibly regulating the expression of several extracellular matrix components. ( 23680354 )
2013
11
A novel mutation in PRDM5 in brittle cornea syndrome. ( 22122778 )
2012
12
Peripartum anesthetic management of a patient with brittle cornea syndrome. ( 21258811 )
2011
13
Mutations in PRDM5 in brittle cornea syndrome identify a pathway regulating extracellular matrix development and maintenance. ( 21664999 )
2011
14
Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness. ( 20485516 )
2010
15
Brittle cornea syndrome associated with a missense mutation in the zinc-finger 469 gene. ( 19661234 )
2010
16
Blue sclera with and without corneal fragility (brittle cornea syndrome) in a consanguineous family harboring ZNF469 mutation (p.E1392X). ( 20938016 )
2010
17
Deleterious mutations in the Zinc-Finger 469 gene cause brittle cornea syndrome. ( 18452888 )
2008
18
A novel technique to treat traumatic corneal perforation in a case of presumed brittle cornea syndrome. ( 17322473 )
2007
19
Mapping of a gene causing brittle cornea syndrome in Tunisian jews to 16q24. ( 17122114 )
2006
20
Brittle cornea syndrome and its delineation from the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI): report on 23 patients and review of the literature. ( 14679583 )
2004
21
Brittle cornea syndrome: an heritable connective tissue disorder distinct from Ehlers-Danlos syndrome type VI and fragilitas oculi, with spontaneous perforations of the eye, blue sclerae, red hair, and normal collagen lysyl hydroxylation. ( 2112090 )
1990

Variations for Brittle Cornea Syndrome 2

UniProtKB/Swiss-Prot genetic disease variations for Brittle Cornea Syndrome 2:

71
# Symbol AA change Variation ID SNP ID
1 PRDM5 p.Tyr107Cys VAR_066393 rs387907111

ClinVar genetic disease variations for Brittle Cornea Syndrome 2:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 ZNF469 NM_001127464.2(ZNF469): c.10016G> A (p.Cys3339Tyr) single nucleotide variant Pathogenic rs387907062 GRCh37 Chromosome 16, 88503978: 88503978
2 ZNF469 NM_001127464.2(ZNF469): c.4174G> T (p.Glu1392Ter) single nucleotide variant Pathogenic rs387907063 GRCh37 Chromosome 16, 88498136: 88498136
3 PRDM5 NM_018699.3(PRDM5): c.946_1623del deletion Pathogenic
4 PRDM5 NM_018699.3(PRDM5): c.1768C> T (p.Arg590Ter) single nucleotide variant Pathogenic rs387907110 GRCh37 Chromosome 4, 121616391: 121616391
5 PRDM5 PRDM5, IVS1DS, G-A, +1 single nucleotide variant Pathogenic
6 PRDM5 NM_018699.3(PRDM5): c.320A> G (p.Tyr107Cys) single nucleotide variant Pathogenic rs387907111 GRCh37 Chromosome 4, 121742481: 121742481
7 PRDM5 PRDM5, 1-BP DEL, 947G deletion Pathogenic
8 PRDM5 PRDM5, IVS1DS, T-C, +2 single nucleotide variant Pathogenic
9 ZNF469 NM_001127464.2(ZNF469): c.9184C> T (p.Arg3062Ter) single nucleotide variant Pathogenic rs764139968 GRCh37 Chromosome 16, 88503146: 88503146
10 ZNF469 ZNF469, 1-BP DEL, 5943A deletion Pathogenic
11 ZNF469 ZNF469, 1-BP DEL, 9527G deletion Pathogenic
12 ZNF469 NM_001127464.2(ZNF469): c.6360delG (p.Gln2121Serfs) deletion Pathogenic/Likely pathogenic rs886044697 GRCh37 Chromosome 16, 88500322: 88500322

Expression for Brittle Cornea Syndrome 2

Search GEO for disease gene expression data for Brittle Cornea Syndrome 2.

Pathways for Brittle Cornea Syndrome 2

GO Terms for Brittle Cornea Syndrome 2

Cellular components related to Brittle Cornea Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix GO:0031012 9.5 COL15A1 COL5A1 COL8A2
2 proteinaceous extracellular matrix GO:0005578 9.43 COL15A1 COL5A1 COL8A2
3 basement membrane GO:0005604 9.33 COL15A1 COL5A1 COL8A2
4 endoplasmic reticulum lumen GO:0005788 9.26 COL13A1 COL15A1 COL5A1 COL8A2
5 collagen trimer GO:0005581 8.92 COL13A1 COL15A1 COL5A1 COL8A2

Biological processes related to Brittle Cornea Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell adhesion GO:0007155 9.46 COL13A1 COL15A1 COL5A1 COL8A2
2 extracellular matrix organization GO:0030198 9.13 COL13A1 COL5A1 COL8A2
3 collagen catabolic process GO:0030574 8.92 COL13A1 COL15A1 COL5A1 COL8A2

Molecular functions related to Brittle Cornea Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sulfotransferase activity GO:0008146 8.96 CHST14 SULT1C2
2 extracellular matrix structural constituent GO:0005201 8.8 COL15A1 COL5A1 COL8A2

Sources for Brittle Cornea Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
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47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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