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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

Phenotypic abnormality
- Abnormality of the integument
  - Abnormality of the skin
    - 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

An Eye into the Aorta: The Role of Extracellular Matrix Regulatory Genes ZNF469 and PRDM5, from Their Previous Association with Brittle Cornea Syndrome to Their Novel Association with Aortic and Arterial Aneurysmal Diseases.

Moore P, Wolf A, Sathyamoorthy M
Int J Mol Sci 2024 May 28;25(11) doi: 10.3390/ijms25115848. PMID: 38892036 Free PMC Article

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

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.

Vithana EN, Aung T, Khor CC, Cornes BK, Tay WT, Sim X, Lavanya R, Wu R, Zheng Y, Hibberd ML, Chia KS, Seielstad M, Goh LK, Saw SM, Tai ES, Wong TY
Hum Mol Genet 2011 Feb 15;20(4):649-58. Epub 2010 Nov 23 doi: 10.1093/hmg/ddq511. PMID: 21098505

See all (17)

Diagnosis

Identification and Management of a Novel PRDM5 Gene Pathologic Variant in a Family With Brittle Cornea Syndrome.

Sklar BA, Pisuchpen P, Bareket M, Milman T, Eagle RC Jr, Minor J, Procopio R, Capasso J, Levin AV, Hammersmith K
Cornea 2023 Dec 1;42(12):1572-1577. Epub 2023 Sep 15 doi: 10.1097/ICO.0000000000003372. PMID: 37713669

Corneal ectasia associated with posterior lamellar opacification.

Yung M, Chen AC, Chung DD, Barrington A, Zhang J, Frausto RF, Magalhaes OA, Aldave AJ
Ophthalmic Genet 2021 Aug;42(4):486-492. Epub 2021 May 18 doi: 10.1080/13816810.2021.1923034. PMID: 34003075

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

Syndromes presenting adducted thumb with/without clubfoot and Dundar syndrome.

Uzak AS, Fryns JP, Dundar M
Genet Couns 2014;25(2):159-69. PMID: 25059014

Brittle cornea syndrome: recognition, molecular diagnosis and management.

See all (29)

Therapy

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

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

See all (3)

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

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

Mutations in the zinc finger protein gene, ZNF469, contribute to the pathogenesis of keratoconus.

Vincent AL, Jordan CA, Cadzow MJ, Merriman TR, McGhee CN
Invest Ophthalmol Vis Sci 2014 Aug 5;55(9):5629-35. doi: 10.1167/iovs.14-14532. PMID: 25097247

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

See all (9)

Clinical prediction guides

Identification and Management of a Novel PRDM5 Gene Pathologic Variant in a Family With Brittle Cornea Syndrome.

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

A role for repressive complexes and H3K9 di-methylation in PRDM5-associated brittle cornea syndrome.

Porter LF, Galli GG, Williamson S, Selley J, Knight D, Elcioglu N, Aydin A, Elcioglu M, Venselaar H, Lund AH, Bonshek R, Black GC, Manson FD
Hum Mol Genet 2015 Dec 1;24(23):6565-79. Epub 2015 Sep 22 doi: 10.1093/hmg/ddv345. PMID: 26395458 Free PMC Article

Syndromes presenting adducted thumb with/without clubfoot and Dundar syndrome.

Uzak AS, Fryns JP, Dundar M
Genet Couns 2014;25(2):159-69. PMID: 25059014

See all (14)

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Brittle cornea syndrome

Definition

Term Hierarchy

Professional guidelines

PubMed

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

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