Audiovestibular phenotype associated with a COL11A1 mutation in Marshall syndrome

Background: Marshall syndrome is a dominant disorder characterized by crani ofacial and skeletal abnormalities, sensorineural hearing loss, myopia, and cataracts, and is associated with splicing mutations in COL11A1. Objective: To determine the auditory and vestibular phenotypes associated w ith a COL11A1 splicing. Design: Clinical otolaryngologic, audiologic, vestibular, and radiologic ev aluations of the auditory and vestibular systems. Subjects: Three affected individuals from a family cosegregating Marshall s yndrome and a COL11A1 splice site mutation. Results: The study subjects have progressive sensorineural hearing loss tha t is predominantly cochlear in origin and asymptomatic dysfunction of the c entral and peripheral vestibular systems. Computed tomography detected no m alformations of temporal bone structures. Conclusions: The observed auditory and vestibular abnormalities are not cau sed by defective morphogenesis of the osseous labyrinth, but by more direct effects of the COL11A1 mutation on the membranous labyrinth and the centra l nervous system. The onset and degree of hearing loss associated with COL1 1A1 mutations are useful clinical features to differentiate Marshall syndro me from the phenotypically similar Stickler syndrome.