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Brittle cornea syndrome

MedGen UID:: 946156
•Concept ID:: CN263128
•: Disease or Syndrome

Synonyms:	BCS1; brittle cornea syndrome; brittle cornea syndrome 1; brittle cornea syndrome type 1; EDS VIB (formerly); Ehlers-Danlos syndrome type 6b; Ehlers-Danlos syndrome type 6B (formerly); kyphoscoliosis type; type VIB Ehlers-Danlos syndrome
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Autosomal recessive inheritance (Orphanet)

Related genes: Gene(s) associated with related conditions. For conditions in a hierarchy, the parent condition will list the genes associated with the children conditions.	ZNF469, PRDM5

Monarch Initiative:	MONDO:0009242
OMIM® Phenotypic series:	PS229200
Orphanet:	ORPHA90354

Definition

A rare, hereditary connective tissue disease characterized by severe ocular manifestations due to extreme corneal thinning and fragility with rupture in the absence of significant trauma, often leading to irreversible blindness. Extraocular manifestations comprise deafness, developmental hip dysplasia, and joint hypermobility. [from ORDO]

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVBrittle cornea syndrome
- CROGVBrittle cornea syndrome 1
- CROGVBrittle cornea syndrome 2

Hereditary disorder of connective tissue
- COL1A1 Associated Connective Tissue Disorder
  - Ehlers-Danlos syndrome
    - Brittle cornea syndrome
      - Brittle cornea syndrome 1
      - Brittle cornea syndrome 2

Professional guidelines

PubMed

Brittle cornea syndrome: recognition, molecular diagnosis and management.

Burkitt Wright EM, Porter LF, Spencer HL, Clayton-Smith J, Au L, Munier FL, Smithson S, Suri M, Rohrbach M, Manson FD, Black GC
Orphanet J Rare Dis 2013 May 4;8:68. doi: 10.1186/1750-1172-8-68. PMID: 23642083 Free PMC Article

See all (1)

Recent clinical studies

Etiology

Bruch's membrane abnormalities in PRDM5-related brittle cornea syndrome.

Porter LF, Gallego-Pinazo R, Keeling CL, Kamieniorz M, Zoppi N, Colombi M, Giunta C, Bonshek R, Manson FD, Black GC
Orphanet J Rare Dis 2015 Nov 11;10:145. doi: 10.1186/s13023-015-0360-4. PMID: 26560304 Free PMC Article

Brittle cornea syndrome ZNF469 mutation carrier phenotype and segregation analysis of rare ZNF469 variants in familial keratoconus.

Davidson AE, Borasio E, Liskova P, Khan AO, Hassan H, Cheetham ME, Plagnol V, Alkuraya FS, Tuft SJ, Hardcastle AJ
Invest Ophthalmol Vis Sci 2015 Jan 6;56(1):578-86. doi: 10.1167/iovs.14-15792. PMID: 25564447

Brittle cornea syndrome: recognition, molecular diagnosis and management.

Keratoconus in Costello syndrome.

Gripp KW, Demmer LA
Am J Med Genet A 2013 May;161A(5):1132-6. Epub 2013 Mar 13 doi: 10.1002/ajmg.a.35816. PMID: 23494969

Mutations in PRDM5 in brittle cornea syndrome identify a pathway regulating extracellular matrix development and maintenance.

Burkitt Wright EMM, Spencer HL, Daly SB, Manson FDC, Zeef LAH, Urquhart J, Zoppi N, Bonshek R, Tosounidis I, Mohan M, Madden C, Dodds A, Chandler KE, Banka S, Au L, Clayton-Smith J, Khan N, Biesecker LG, Wilson M, Rohrbach M, Colombi M, Giunta C, Black GCM
Am J Hum Genet 2011 Jun 10;88(6):767-777. doi: 10.1016/j.ajhg.2011.05.007. PMID: 21664999 Free PMC Article

See all (16)

Diagnosis

New ZNF469 Mutations in Spanish Siblings With Brittle Cornea Syndrome.

García de Oteyza G, Fernández Engroba J, Charoenrook V
Cornea 2023 Jul 1;42(7):894-898. Epub 2023 Apr 24 doi: 10.1097/ICO.0000000000003280. PMID: 37098112

Brittle cornea syndrome: A tale of three brothers.

Mandlik K, Betdur RA, Rashmita R, Narayana S
Indian J Ophthalmol 2022 Jul;70(7):2594-2597. doi: 10.4103/ijo.IJO_2894_21. PMID: 35791165 Free PMC Article

Brittle cornea syndrome: a case report and review of the literature.

Wan Q, Tang J, Han Y, Xiao Q, Deng Y
BMC Ophthalmol 2018 Sep 18;18(1):252. doi: 10.1186/s12886-018-0903-2. PMID: 30227830 Free PMC Article

Ocular genetic disease in the Middle East.

Khan AO
Curr Opin Ophthalmol 2013 Sep;24(5):369-78. doi: 10.1097/ICU.0b013e3283638374. PMID: 23846189

Brittle cornea syndrome: recognition, molecular diagnosis and management.

See all (28)

Therapy

Corneal Perforation After Corneal Cross-Linking in Keratoconus Associated With Potentially Pathogenic ZNF469 Mutations.

Zhang W, Margines JB, Jacobs DS, Rabinowitz YS, Hanser EM, Chauhan T, Chung D, Bykhovskaya Y, Gaster RN, Aldave AJ
Cornea 2019 Aug;38(8):1033-1039. doi: 10.1097/ICO.0000000000002002. PMID: 31107761 Free PMC Article

Corneal Cross-Linking for Brittle Cornea Syndrome.

Kaufmann C, Schubiger G, Thiel MA
Cornea 2015 Oct;34(10):1326-8. doi: 10.1097/ICO.0000000000000577. PMID: 26266434

Peripartum anesthetic management of a patient with brittle cornea syndrome.

Ioscovich A, Grisaru-Granovsky S, Halpern S, Shapiro Y
Arch Gynecol Obstet 2011 Mar;283 Suppl 1:49-52. Epub 2011 Jan 22 doi: 10.1007/s00404-011-1838-5. PMID: 21258811

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Prognosis

A novel homozygous ZNF469 variant causing brittle cornea syndrome is associated with corneal ectasias in heterozygous carriers.

Arce-González R, Chacon-Camacho OF, Ordoñez-Labastida V, Graue-Hernandez EO, Navas-Pérez A, Zenteno JC
Int Ophthalmol 2023 Mar;43(3):807-815. Epub 2022 Sep 1 doi: 10.1007/s10792-022-02481-5. PMID: 36048286

Corneal Cross-Linking for Brittle Cornea Syndrome.

Kaufmann C, Schubiger G, Thiel MA
Cornea 2015 Oct;34(10):1326-8. doi: 10.1097/ICO.0000000000000577. PMID: 26266434

Brittle cornea syndrome ZNF469 mutation carrier phenotype and segregation analysis of rare ZNF469 variants in familial keratoconus.

Brittle cornea syndrome associated with a missense mutation in the zinc-finger 469 gene.

Christensen AE, Knappskog PM, Midtbø M, Gjesdal CG, Mengel-From J, Morling N, Rødahl E, Boman H
Invest Ophthalmol Vis Sci 2010 Jan;51(1):47-52. Epub 2009 Aug 6 doi: 10.1167/iovs.09-4251. PMID: 19661234

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.

Al-Hussain H, Zeisberger SM, Huber PR, Giunta C, Steinmann B
Am J Med Genet A 2004 Jan 1;124A(1):28-34. doi: 10.1002/ajmg.a.20326. PMID: 14679583

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Clinical prediction guides

Whole-Exome Sequencing Identifies Novel Compound Heterozygous ZNF469 Mutations in Two Siblings with Mild Brittle Cornea Syndrome.

Rolvien T, Kornak U, Linke SJ, Amling M, Oheim R
Calcif Tissue Int 2020 Sep;107(3):294-299. Epub 2020 Jul 15 doi: 10.1007/s00223-020-00721-3. PMID: 32671420 Free PMC Article

Brittle cornea syndrome: a case report and review of the literature.

Wan Q, Tang J, Han Y, Xiao Q, Deng Y
BMC Ophthalmol 2018 Sep 18;18(1):252. doi: 10.1186/s12886-018-0903-2. PMID: 30227830 Free PMC Article

Bruch's membrane abnormalities in PRDM5-related brittle cornea syndrome.

Brittle cornea syndrome ZNF469 mutation carrier phenotype and segregation analysis of rare ZNF469 variants in familial keratoconus.

Brittle cornea syndrome associated with a missense mutation in the zinc-finger 469 gene.

See all (14)