Clinical characteristics: Usher syndrome type I (USH1) is characterized by congenital, bilateral, profound sensorineural hearing loss, vestibular areflexia, and adolescent-onset retinitis pigmentosa (RP). Unless fitted with a cochlear implant, individuals do not typically develop speech. RP, a progressive, bilateral, symmetric degeneration of rod and cone functions of the retina, develops in adolescence, resulting in progressively constricted visual fields and impaired visual acuity.

Diagnosis/testing: The diagnosis of USH1 is established in a proband using electrophysiologic and subjective tests of hearing and retinal function. Identification of biallelic pathogenic variants in one of six genes – MYO7A, USH1C, CDH23, PCDH15, USH1G, and CIB2 – establishes the diagnosis if clinical features are inconclusive. Possible digenic inheritance has been reported in a few families.

Management: Treatment of manifestations: In infants: an initial trial of hearing aids to stimulate residual hearing and accustom the infant to auditory stimulation. Cochlear implantation should be considered as young as medically feasible. Sign language and tactile signs (once visual loss occurs) for families who choose non-auditory communication. Specialized training from educators of the hearing impaired. Vestibular compensation therapy for children with residual balance function and sensory substitution therapy for individuals with complete absence of vestibular function. Standard treatments for retinitis pigmentosa.

Surveillance: Annual audiometry and tympanometry in those with cochlear implant or hearing aids to assure adequate auditory stimulation. Annual otoscopic exam with tympanometry in children with profound loss to evaluate for chronic otitis media. Annual ophthalmologic evaluation, fundus photography, visual acuity, visual field testing, electroretinography, optical coherence tomography, and fundus autofluorescence from age 20 years.

Agents/circumstances to avoid: Competition in sports requiring acute vision and/or good balance may be difficult and possibly dangerous. Because of the high risk for disorientation when submerged in water, swimming needs to be undertaken with caution. Progressive loss of peripheral vision impairs the ability to safely drive a car.

Evaluation of relatives at risk: The hearing of at-risk sibs should be assessed as soon after birth as possible to allow early diagnosis and treatment of hearing loss.

Genetic counseling: USH1 is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the USH1-causing pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal diagnosis for a pregnancy at increased risk, and preimplantation genetic testing are possible.