branchiootorenal syndrome; branchio-oto-renal syndrome; BOR syndrome; Melnick-Fraser syndrome

Introduction

branchiootic syndrome with renal dysplasia

Pathology

• abnormal development of the second branchial arch
• malformations of the ears & kidneys
• various combinations of
  • preauricular pits
  • branchial fistulae or cysts
  • lacrimal duct stenosis
  • structural defects of the outer, middle, or inner ear
  • hearing loss may be due to mondini type cochlear defect & stapes fixation
  • renal dysplasia

Genetics

• autosomal dominant
• mutations in 3 genes, EYA1, SIX1, & SIX5, are known to cause branchiootorenal syndrome
• ~40% of cases involve EYA1 mutations
• SIX1 & SIX5 mutations are much less common causes
• associated with defects in EYA1 (type 1)
  • Melnick-Fraser syndrome)
  • penetrance is high
  • expressivity can be extremely variable
• associated with defects in SIX1
• associated with defects in SIX5 (type 2)

Clinical manifestations

• asthenic habitus
• long narrow facies
• constricted palate
• deep overbite
• myopia
• hearing loss

More general terms

• branchiootic syndrome

Additional terms

• cryptophthalmos syndrome (Fraser syndrome)
• otofaciocervical syndrome

Database

• OMIM: https://mirror.omim.org/entry/113650
• OMIM: https://mirror.omim.org/entry/610896