Usher Syndrome

Definition and epidemiology

Usher syndrome is an autosomal recessive condition in which sensorineural hearing loss is accompanied by a progressive retinal degeneration called retinitis pigmentosa (RP). It is the commonest inherited cause of combined sight and hearing loss and accounts for about half of people under 65 with deafblindness (Castiglione and Möller, 2022). Its prevalence is estimated at about 1 in 29,000, with reported rates ranging from 1 to 17 per 100,000 (Koenekoop et al., 2026; Castiglione and Möller, 2022).

Three clinical types are described. Type 1 has congenital bilateral profound sensorineural loss, vestibular areflexia and RP beginning in childhood; type 2 has congenital moderate to severe, relatively stable loss, normal vestibular function and RP usually noticed in the teens; type 3 has loss that is usually mild in childhood and then progresses, vestibular function that is normal at first but may decline, and RP beginning in the teens (Castiglione and Möller, 2022).

Atypical forms with mild hearing loss and variable retinal involvement, linked to genes such as CEP250, CEP78 and ARSG, have also been reported; the label ‘type 4’ has not been widely accepted (Castiglione and Möller, 2022). Among children with hearing loss, the proportion with pathogenic variants in Usher genes was 3-6% in older estimates and 11% in a study from Oregon, USA (Koenekoop et al., 2026).

Symptoms and signs

In type 1 the hearing loss is congenital, bilateral and profound, and the baby does not pass the newborn hearing screen. In type 2 the loss is congenital and moderate to severe, with a sloping pattern that is mild to moderate at low frequencies and severe to profound at high frequencies, and it is relatively stable. In type 3 the loss is usually mild in childhood and progresses, often reaching severe to profound levels in the third decade of life (Castiglione and Möller, 2022).

Because of vestibular areflexia, a baby with type 1 may seem floppy; sitting and crawling are delayed, and independent walking usually starts between 18 months and 2 years. Older children may seem clumsy and find walking on narrow surfaces and learning to ride a bicycle difficult (Koenekoop et al., 2026; Castiglione and Möller, 2022). This is a congenital form of bilateral vestibulopathy; while vision is good it is largely compensated by sensory substitution, but it becomes more obvious as sight declines and in the dark.

The first signs of RP are night blindness and sensitivity to light. Rods are affected first, so vision in the dark worsens and the visual field narrows from the periphery inwards; cones are involved later. ‘Tunnel vision’, with a field of 5-10 degrees, is common at 30-40 years but can appear at 20-30. Central vision can be preserved for a long time; cataract and cystoid macular oedema can reduce central vision, but both are treatable (Koenekoop et al., 2026).

Causes and risk factors

In type 1 the gene most often involved is MYO7A (60-70%), followed by CDH23 (10-20%), PCDH15 (7-15%), USH1C (5-10%) and, rarely, USH1G. CIB2, once reported as a type 1 gene, is no longer considered an Usher gene (Koenekoop et al., 2026). In type 2, USH2A accounts for 80-90% of cases, with ADGRV1 and WHRN less common. The main known gene for type 3 is CLRN1 (Toms et al., 2020; Castiglione and Möller, 2022).

The proteins encoded by these genes form complexes that work together in the inner ear, in the structures linking hair cell stereocilia and turning mechanical stimulation into electrical signals, and in the retina, in the ciliary region of photoreceptors (Toms et al., 2020). This shared function explains why hearing, balance and sight are affected in one syndrome. Some variants in the same genes cause hearing loss alone without retinal involvement; non-syndromic losses related to MYO7A and CDH23 are examples (Castiglione and Möller, 2022).

Inheritance is autosomal recessive: when both parents are carriers, each pregnancy has a 25% chance of an affected child. Consanguineous marriage increases the chance of recessive conditions, so genetic assessment is particularly important for every child with congenital hearing loss in communities where it is relatively common.

Audiological and clinical assessment

Because types 1 and 2 are congenital, most children are picked up by newborn hearing screening, but the syndrome diagnosis can be delayed because RP becomes obvious only years later. In a baby with congenital severe to profound loss, demonstrating vestibular areflexia is the key audiological clue to type 1 before any retinal signs appear, and it prompts genetic testing.

• ABR, OAEs and pure-tone audiometry: in type 1 the ABR shows no response or a very high threshold, and OAEs are absent. Type 2 shows a sloping sensorineural pattern, mild to moderate at low frequencies and severe to profound at high frequencies; in type 3 a milder early loss progresses on follow-up (Castiglione and Möller, 2022).
• Tympanometry: the middle ear is normal. Annual otoscopy and tympanometry are advised for children using hearing aids or a CI to screen for chronic middle ear problems (Koenekoop et al., 2026).
• Vestibular tests: video head impulse test (vHIT), caloric and rotational testing and vestibular evoked myogenic potentials (VEMP): bilateral areflexia is expected in type 1, normal responses in type 2 and variable, declining responses in type 3.
• Eye assessment: electroretinography (ERG), optical coherence tomography (OCT), visual fields and fundus autofluorescence; ERG can show retinal dysfunction before symptoms. An annual eye examination is advised even before symptoms (Koenekoop et al., 2026).
• Genetic testing: a hearing loss or retinal panel including MYO7A, CDH23, PCDH15, USH1C, USH1G, USH2A, ADGRV1, WHRN and CLRN1.

The differential diagnosis includes non-syndromic hearing loss linked to the same genes, CHARGE syndrome with coloboma and vestibular findings, and mitochondrial disorders affecting both hearing and sight. For follow-up, annual audiometry and tympanometry are advised for people using hearing aids or a CI (Koenekoop et al., 2026).

Treatment and audiological rehabilitation

In type 1 the baby is first fitted with hearing aids to stimulate residual hearing, but with profound loss aids are usually inadequate, and a CI should be considered as early as medically feasible, typically before the age of one (Koenekoop et al., 2026). Castiglione and Möller (2022) recommend implantation at 6-12 months, report age at surgery as the most important prognostic factor and stress that bilateral implantation is strongly supported for rehabilitation. Because sight will decline, reliance on visual cues such as lipreading and signing will fall, which makes auditory access all the more valuable for these children.

A systematic review of 33 studies and 187 patients found that a CI benefited most patients and identified early implantation as an important factor (Cornwall et al., 2024). Another review of 15 studies found better results in those implanted young and poorer sentence recognition after long auditory deprivation (Davies et al., 2021). Some reports describe weaker implant performance with PCDH15 variants, but the evidence is limited (Castiglione and Möller, 2022). Timely auditory-verbal therapy after implantation is needed for speech development (Koenekoop et al., 2026).

In type 2, bilateral hearing aids are fitted soon after diagnosis, and with early rehabilitation language develops well; if the loss worsens with age in later life, a CI may be considered. In type 3, hearing aids are used first and a CI is considered as the loss progresses; in Swedish data most people with type 3 were implanted at 30-40 years, with good outcomes reported for CLRN1-related cases (Castiglione and Möller, 2022).

The communication approach is chosen with the family and with the course of sight loss in mind. Sign language can be learnt from birth alongside hearing aids or a CI; as sight declines, a move from visual to tactile signing may be needed (Koenekoop et al., 2026). Castiglione and Möller (2022) recommend that children learn sign language as a second language. A remote microphone system, good lighting and high contrast support both auditory and visual access.

There is no approved treatment for RP yet. Gene replacement, gene editing, antisense oligonucleotide and small-molecule approaches are in development or clinical trials (Toms et al., 2020). The first gene therapy trial for MYO7A was stopped in 2018, a new phase I/II dual AAV vector study is under way in adults, and the antisense oligonucleotide ultevursen for USH2A is in phase IIb (Koenekoop et al., 2026). These studies are promising, but their results are not yet conclusive and they have not become routine treatment; decisions and referrals rest with the ophthalmologist.

Impact on quality of life and advice

An Usher diagnosis can mean that a family who has spent years adapting to hearing loss must face a second sensory loss. A clear explanation of the diagnosis and expected course, psychological support and contact with families with similar experience help. As the visual field narrows in adolescence, new decisions may be needed about career choice, driving and independent travel.

Night blindness and a narrowing field, combined with vestibular areflexia, increase the risk of falls in the dark. Good lighting at home and school, clearly marked step edges and, when needed, a white cane and orientation and mobility training are advised. Families should be told that children with type 1 can lose their sense of direction when swimming in dark or murky water and should swim under supervision.

At school, good lighting on the teacher’s face, front-row seating, a remote microphone system and skills training for sight loss (enlarged materials and, where needed, Braille) support learning (Koenekoop et al., 2026). Assessing siblings and offering the family genetic counselling allow informed decisions about future pregnancies.