Details of Disease

General Information of Disease (ID: DISIPQ53)

• Disease Name: Branchio-oto-renal syndrome
• Synonyms: Branchio oto renal syndrome; bor syndrome; branchiootorenal dysplasia; Melnick-Fraser syndrome; Branchio-Oto-renal syndrome; branchiootorenal syndrome; Branchio-otorenal dysplasia; branchio-oto-renal syndrome
• Definition: A syndrome characterized by branchial arch anomalies (branchial clefts, fistulae, cysts), hearing impairment (malformations of the auricle with pre-auricular pits, conductive or sensorineural hearing impairment), and renal malformations (urinary tree malformation, renal hypoplasia or agenesis, renal dysplasia, renal cysts).|(From orphanet): Branchiootorenal (BOR) syndrome is characterized by branchial arch anomalies (branchial clefts, fistulae, cysts), hearing impairment (malformations of the auricle with pre-auricular pits, conductive or sensorineural hearing impairment), and renal malformations (urinary tree malformation, renal hypoplasia or agenesis, renal dysplasia, renal cysts). Prevalence is 1/40,000. Renal involvement can lead to chronic renal insufficiency. The expression of the disease varies widely from one family to another and among individuals of the same family. Some families do not present with renal abnormalities or a urinary tree malformation. BOR syndrome is transmitted in an autosomal dominant manner. The causative gene, EYA1, is located on the long arm of chromosome 8. Point mutations and deletions in EYA1 have been identified in approximately 40% of affected individuals. Mutations have also been identified in the SIX1 and SIX5 genes, the products of which interact with EYA1 to form transcription factor complexes. Prenatal testing can be proposed to families in which the disease-causing mutation has been identified, but genetic counseling is difficult because of the clinical heterogeneity between individuals. Management of affected patients includes excision of branchial fistulae or cysts, hearing aids and education programs appropriate for the hearing impaired, and follow-up by a nephrologist. Dialysis or renal transplantation may be required.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISD0WVL: Multiple congenital anomalies/dysmorphic syndrome without intellectual disability
  DIS3HIWD: Autosomal dominant disease
  DISIPQ53: Branchio-oto-renal syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0007029
  MESH ID: D019280
  UMLS CUI: C0265234
  MedGen ID: 82693
  Orphanet ID: 107
  SNOMED CT ID: 290006

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CDCA8	TT04YCM	Strong	Genetic Variation	[1]
EYA2	TTUY9C6	Strong	Biomarker	[2]
RBCK1	TTIKUVC	Strong	Biomarker	[3]
TFAP2A	TTDY4BS	Strong	Biomarker	[4]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SIX5	OTT1I9WY	Supportive	Autosomal dominant	[5]
EYA4	OTINGR3Z	Strong	Biomarker	[6]
SALL1	OTYYZGLH	Strong	Biomarker	[7]
SHARPIN	OTU1J2KH	Strong	Genetic Variation	[3]
EYA1	OTHU807A	Definitive	Autosomal dominant	[8]
SIX1	OT70YYWM	Definitive	Autosomal dominant	[8]

References

• [1] Detection of a megabase deletion in a patient with branchio-oto-renal syndrome (BOR) and tricho-rhino-phalangeal syndrome (TRPS): implications for mapping and cloning the BOR gene.Genomics. 1996 Jan 15;31(2):201-6. doi: 10.1006/geno.1996.0032.
• [2] Structure-function analyses of the human SIX1-EYA2 complex reveal insights into metastasis and BOR syndrome.Nat Struct Mol Biol. 2013 Apr;20(4):447-53. doi: 10.1038/nsmb.2505. Epub 2013 Feb 24.
• [3] Sipl1 and Rbck1 are novel Eya1-binding proteins with a role in craniofacial development.Mol Cell Biol. 2010 Dec;30(24):5764-75. doi: 10.1128/MCB.01645-09. Epub 2010 Oct 18.
• [4] Reduced TFAP2A function causes variable optic fissure closure and retinal defects and sensitizes eye development to mutations in other morphogenetic regulators.Hum Genet. 2009 Dec;126(6):791-803. doi: 10.1007/s00439-009-0730-x.
• [5] Branchiootorenal Spectrum Disorder. 1999 Mar 19 [updated 2018 Sep 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [6] A comparative study of Eya1 and Eya4 protein function and its implication in branchio-oto-renal syndrome and DFNA10.J Assoc Res Otolaryngol. 2004 Sep;5(3):295-304. doi: 10.1007/s10162-004-4044-3. Epub 2004 Jun 24.
• [7] Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: results of the ESCAPE study. J Am Soc Nephrol. 2006 Oct;17(10):2864-70. doi: 10.1681/ASN.2006030277. Epub 2006 Sep 13.
• [8] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.