Paediatric Usher syndrome: Navigating a Challenging Landscape

Abstract

Usher syndrome, a genetic condition characterized by deafness and progressive vision loss or prospective deafblindness, challenges traditional deafblindness definitions and assessment approaches. While early diagnosis through genetic testing has become more common, the progressive nature of vision loss in Usher syndrome often means it is overlooked in traditional paediatric deafblindness prevalence estimates. This perpetuates underrepresentation, resulting in inadequate resources and support for individuals and families living with this diagnosis. This article explores the complexities of assessing and supporting children with Usher syndrome, and their families, within the framework of deafblindness, highlighting the importance of early identification, improved professional awareness, and tailored interventions.

Introduction

Usher syndrome causes a complex sensory disability characterized by dual diagnoses of deafness and vision loss. With an estimated prevalence of between 4 and 17 per 100,000 (Boughman et al., 1983; Kimberling et al., 2010), Usher syndrome accounts for approximately half of all cases of hereditary deafblindness (Ben-Rebeh et al., 2016; Castiglione & Möller, 2022). Usher syndrome typically causes bilateral congenital moderate to profound sensorineural hearing loss (SNHL) in conjunction with progressive vision loss in childhood to early adolescence in the form of retinitis pigmentosa (RP). In some cases, Usher syndrome can also be associated with vestibular dysfunction, resulting in difficulties with balance and gross motor skill development (Cushing & Papsin, 2018).

The deafblindness associated with Usher syndrome can be considered prospective, with early onset deafness and later onset vision loss. This significantly impacts aspects of childhood development, including communication, socialization, mobility, daily living, and ultimately child and family quality of life (Li et al., 2022). Importantly, the impact of Usher syndrome is more than the sum of deafness and blindness, and rather should be considered multiplicative (Ferrell et al., 2014). The combined losses associated with Usher syndrome occur on a spectrum (Deasy & Lyddy, 2006), adding further complexities to the lived experience and management of the condition. Although there is currently no conclusive medical treatment for Usher syndrome, management recommendations may include hearing aids, cochlear implantation, physical therapy, and compensatory rehabilitative training (Castiglione & Möller, 2022; Ellis & Hodges, 2013).

Historically, the diagnosis of Usher syndrome has relied on a clinical diagnosis of RP in individuals with an existing diagnosis of deafness. However, due to the progressive nature of RP, symptoms such as night blindness, tunnel vision, or difficulty seeing in low light may be dismissed for years before ophthalmic investigations are pursued by families (Kamde & Anjankar, 2023). Consequently, the early signs of dual sensory loss, with or without vestibular dysfunction, may go unnoticed, resulting in a misdiagnosis of isolated deafness (Bruce & Borders, 2015).

In the early stages of Usher syndrome, when the functional impact of vision loss may be minimal, the family is asked to accept a prospective dual/triple sensory diagnosis (vision/hearing/vestibular), often with support offered and tailored for deafness only. Consequently, children with Usher syndrome may not be included in prevalence estimates of deafblindness until later in life, leading to inadequate identification (Meekins-Doherty et al., 2023). Not accounting for Usher syndrome ultimately results in an underestimation of the scope of the childhood population who need support for multisensory involvement.

This article will explore the challenges faced by individuals and families with Usher syndrome as they navigate assessment, diagnosis, and the subsequent impacts. We highlight the challenge of applying existing deafblindness definitions; the challenge of assessments and ensuring timely diagnosis; eligibility for and the provision of specialized transdisciplinary support; and emphasize the psychosocial impacts of Usher syndrome on individuals and their families.

The challenge of applying existing deafblindness definitions to Usher syndrome

The conceptualization of Usher syndrome within existing deafblindness definitions holds important implications for research, policy, and practice. The prospective nature of deafblindness associated with Usher syndrome challenges currently accepted definitions and raises questions regarding accurate classification. We have previously highlighted the importance of early identification, the negative effects of underrepresentation in prevalence estimates, and the unsuitable conceptualization of Usher syndrome within existing deafblindness definitions (Meekins-Doherty et al., 2023). Although significant efforts have been made towards developing a unified definition (Ask Larsen & Damen, 2014) and discussions are ongoing (Deelkracht, 2023), it remains unclear where paediatric Usher syndrome fits into these definitions.

Equity and equality of support require an accurate estimate of the size of the group in need (United Nations Children’s Fund, 2021). The definition and classification of Usher syndrome directly impact access to necessary services and support. A child with Usher syndrome who has SNHL (prior to the onset of vision loss) may only receive support for their deafness diagnosis. However, Usher syndrome is far more complex, encompassing multiple developmental facets, with individuals requiring timely and comprehensive support compared to those who do not face prospective deafblindness (Stiff et al., 2020).

As evident from the 2022 approach by the World Federation of the Deafblind’s (WFDB), contemporary deafblindness prevalence estimates and resource distribution are based on the current diagnoses, which neglects the prospective sensory impact characteristic of Usher syndrome. However, this approach fails individuals and families with Usher syndrome, as despite the later onset of the combined impairment, they require multimodal intervention near or at the time of diagnosis (Johansen et al., 2024). Neglecting to consider a child with Usher syndrome as having a form of deafblindness (before the onset of combined sensory impairment) leads to inadequate resource allocation and delayed support.

We therefore emphasize the importance of including children with Usher syndrome in paediatric deafblind prevalence figures at diagnosis to highlight the complexity of services they require. To ensure inclusion, suitable definitions must be applied, and we recommend the revised Nordic Definition of Deafblindness, which states,

Deafblindness is a combined vision and hearing impairment of such severity that it is hard for the impaired senses to compensate for each other. Thus, deafblindness is a distinct disability. To varying degrees, deafblindness limits activities and restricts full participation in society. It affects communication, access to information, orientation, and the ability to move around freely and safely. There is a high risk that the physical and psychological health, as well as social life, will be affected . . . in order to enable the individual to use their potential capacity and resources, society is required to facilitate specialised services. (Nordic Welfare Centre, personal communication, 11 September 2024)

In the case of Usher syndrome, the value of considering the Nordic definition lies in the fact that it recognizes the impact of deafblindness on the person. However, it does not fully address the complexities of prospective deafblindness.

Professionals must be aware of the deficiencies in existing deafblindness definitions when considering Usher syndrome. It is critical to make an appeal on behalf of the child who is diagnosed with Usher syndrome who will become deafblind and to recognize, ‘the need to promote and protect the human rights of all persons with disabilities, including those who require more intensive support’ (United Nations, 2007, p. 2). Early support beginning at diagnosis equips both children and their families with the skills and assistance needed to manage progressive vision loss effectively. This is in line with the WFDB’s recommendation for referral to support services as early as possible (WFDB, 2022). With early support, children with Usher syndrome can fully participate in education and social settings, which positively impacts their long-term outcomes, including employability and quality of life (Cmar, 2015; Ehn et al., 2016, 2018).

Significant research is currently underway to develop a thorough understanding of deafblindness (Paramasivam et al., 2021) through the use of the International Classification of Functioning, Disability and Health (ICF) (World Health Organization, 2001). This international, groundbreaking work in developing an ICF Core Set for deafblindness will inform policy, health, research, and social supports relating to people with deafblindness (Paramasivam et al., 2023). While a children and youth core set may be developed in the future, the current research findings are applicable only to adults and do not include children under 18 years (Jaiswal et al., 2024). This highlights the timely importance of raising the needs of children with Usher syndrome, who are in the unique position of developing with prospective deafblindness, as they and their families will have distinct needs and challenges from those of adults.

The challenge of assessment and timely diagnosis of Usher syndrome

Due to its subtle clinical presentation with progressive functional impact, a combined clinical-functional approach (Ask Larsen & Damen, 2014) and genetic assessment (Li et al., 2022) are recommended when assessing a child for Usher syndrome. Although the necessity for a combined approach has been highlighted (Deelkracht, 2023), the implementation of this approach is not applied consistently. The sole reliance on a single assessment approach risks the nonidentification of Usher syndrome. For instance, vestibular dysfunction and progressive vision loss, which are both key features of Usher syndrome, might be overlooked if assessments are limited only to hearing.

We define functional impact using current approaches used by the WFDB (2022), where individuals with deafblindness or their proxies (e.g., parents and/or carers) report of function to represent the impact of the condition on daily life. Functional assessment questionnaires are embedded within many population-level health and demographic surveys and are foundational to contemporary estimates of deafblindness prevalence (e.g., WFDB approaches published in 2018 and 2022). A commonly used tool is the Washington Short Set (Washington Group on Disability Statistics, 2022). However, the use of functional assessment questionnaires poses challenges for accurate prevalence estimates of Usher syndrome-related deafblindness prevalence. Depending on the stage of progression of an individual’s vision loss, questionnaire responses may indicate that the individual is not yet considered deafblind. This is particularly apparent in the paediatric Usher syndrome population, who will not meet functional deafblind criteria until later in life.

Clinical assessments typically involve assessment of hearing such as tympanometry, auditory brainstem response testing, audiometry, and otoacoustic emissions testing, and for vision, visual acuity, visual fields, and electrophysiology. Currently, all children identified as having SNHL are recommended for a clinical ophthalmic evaluation, to establish a visual baseline for possible dual sensory involvement, including pre-clinical retinal findings in children with Usher syndrome (Brodie et al., 2021). However, clinical assessment poses challenges for children who may not be able to communicate about sensory loss or cooperate with testing (Suppiej et al., 2019). While early clinical assessment is recommended, practically a child’s understanding of testing, participation, and cooperation may affect the conclusions reached. Clinical environments must be tailored for children and their families, and staffed by paediatric specialists; in the case of electrophysiology, paediatric anaesthesiology may also be required.

While electrophysiology is recognized in the suite of clinical testing for Usher syndrome, disagreement exists in the literature regarding how well electrophysiology captures prospective cases of deafblindness. West et al. (2015) supported the role of electrophysiology in early diagnosis. However, this contrasts with work by Brodie and colleagues, who identified children with genetic findings pointing to Usher syndrome. In addition, electrophysiology alone cannot distinguish Usher syndrome from non-syndromic RP or other retinal dystrophies. As such, a comprehensive diagnostic approach that includes audiological evaluation, vestibular assessment, and genetic testing is essential to support an accurate diagnosis (Koenekoop et al., 1999).

The limitations of both functional and clinical assessments highlight the value of prompt genetic testing as part of the combined approach for early diagnosis of Usher syndrome, even before RP symptoms become apparent (Brodie et al., 2021; Imizcoz et al., 2023). Timely and efficient genetic diagnostic services must be available to children who are born deaf (Brodie et al., 2021; Li et al., 2022). Currently, genetic testing in the form of multi-gene hearing loss panel testing, or broader exome/genome sequencing, is becoming embedded in the clinical management of paediatric non-syndromic deafness (Li et al., 2022).

Inclusion of genetics in the combined assessment approach can facilitate an early diagnosis, which parents report as beneficial in reducing the emotional burden associated with a diagnosis, while also supporting informed treatment and management decisions for their children (Johansen et al., 2024). Early diagnosis can help set family expectations; predict prognosis for hearing and involvement of other sensory systems; allow prioritization of specialized imaging not otherwise recommended for children with isolated deafness; and plan intervention strategies (Alford et al., 2014; Moeller, 2000; Yoshinaga-Itano et al., 1998). Families should also be provided with counselling about potential positive and negative implications of genetic testing (Milunsky & Milunsky, 2015). During the time of decision-making around testing and diagnosis, clinicians should provide culturally relevant and linguistically appropriate counselling and make timely referrals to specialists and support services.

Genetic testing is useful for distinguishing between conditions with Usher-like features when considering differential diagnoses. These features may include RP with a non-genetic cause of deafness, such as congenital infections (Cohen et al., 2014); a non-syndromic presentation of RP (Fahim et al., 2000) and/or deafness (Shearer et al., 1999), or conditions affecting systems other than those typically implicated in Usher syndrome, such as Heimler syndrome (OMIM: 234580) (Ratbi et al., 2015). As such, careful consideration of ocular and auditory systems, non-ocular and non-auditory systems, noting family history, and genetic testing can assist in clarifying a diagnosis and supporting informed genetic counselling.

Usher syndrome is associated with multiple causative genes inherited in an autosomal recessive pattern (Castiglione & Möller, 2022). While molecular (genetic) diagnostic rates for Usher syndrome continue to improve, they remain below 100% (Bonnet et al., 2016; Fuster-García et al., 2018). Adding to diagnostic complexity, certain genes linked to Usher syndrome have also been associated with non-syndromic autosomal dominant deafness (Watanabe et al., 2024), autosomal recessive deafness (Liao et al., 2025), and autosomal recessive retinopathy (Toualbi et al., 2020).

Therefore, a careful review of the current literature regarding the specific variant and gene in a given family is essential before providing genetic counselling. Non-genetic healthcare professionals ordering these tests may benefit from specialist genetic consultation for result interpretation. Given the clinical heterogeneity and potential for alternative diagnoses, a broader testing approach is advised (Koenekoop et al., 2020) with consideration of the expected diagnostic yield of a given panel of genes, available resources, and potential unexpected results (Hofmann, 2016). A multigene Usher syndrome panel, a broader inherited retinal disease or hereditary hearing loss panel, or a targeted exome approach may increase the likelihood of a genetic diagnosis while minimizing the likelihood of the identification of variants of uncertain significance or findings unrelated to the individual or family presentation. The complexity and variability in diagnosing conditions with Usher-like features means effective genetic counselling is needed to navigate the diagnostic process, interpret results accurately, and provide tailored support to individuals with Usher syndrome and their families.

While the benefits of genetic testing can be appreciated, it is important to note that there are significant consequences related to the genetic outcomes that require careful consideration. For many families, a diagnosis of a syndrome impacting two senses, with no defined timeline for deteriorating vision loss, can be devastating. Some families may prefer not to source this additional information due to concerns regarding potential discrimination or anxiety and well-being, as there are currently no established treatments that significantly alter the disease course (Pereira et al., 2023; Tarini et al., 2009). As such, it is crucial that families who receive a genetic diagnosis are provided with adequate support, such as through the provision of genetic counselling.

Given the deafblindness associated with Usher syndrome, optimizing sensory function is crucial, and early diagnosis that facilitates timely management is vital in achieving this goal (Brodie et al., 2021). In many high-income countries, a diagnosis of deafness may be made very early in life as part of a newborn hearing screening programme. This timely identification ensures that deafness can be effectively managed through early interventions including cochlear implantation and hearing aid fitting (Ching & Leigh, 2020; Koenekoop et al., 2020). These strategies, alongside other communication options and therapies, provide crucial early access to language and are foundational for communication development (Brodie et al., 2021). Furthermore, addressing vestibular dysfunction early yields proportionally better gross motor outcomes (Lacour & Bernard-Demanze, 2015). Importantly, in relation to vision, a delayed diagnosis can be negative, resulting in late access to vision-related services that are essential for skill development and development of coping strategies necessary for achieving self-actualization in adulthood.

Providing specialized, transdisciplinary support

Individuals with Usher syndrome require a coordinated, transdisciplinary approach by health and support services including medical specialists (paediatrician, geneticist, genetic counsellor, otolaryngologist); vision and eye specialists (optometrist, orthoptist, ophthalmologist); allied health professionals (speech pathologist, audiologist, psychologist occupational therapist, orientation and mobility specialist, physiotherapist); and specialist educators (teacher of the deaf, teacher of blind/low vision, deafblind consultant). Although there is currently no effective medical treatment for Usher syndrome, supports such as hearing aids, cochlear implantation, physical therapy, and compensatory rehabilitative training (Castiglione & Möller, 2022; Ellis & Hodges, 2013) can dramatically and positively influence outcomes (Stiff et al., 2020).

Given the complex nature of Usher syndrome, the outcome of a combined assessment approach is critical to ensure tailored support for SNHL, vestibular issues, and preparation for vision loss. Robust eligibility criteria that capture both clinical and functional impacts must be applied. However, legislators currently default to judging an individual’s eligibility for funded support (such as educational support) based on the outcome of clinical assessments. This approach is certainly problematic in Usher syndrome, especially in the case of children. Families of children with prospective deafblindness require specialized, transdisciplinary support at the point of diagnosis. Unfortunately, reliance on clinical assessment outcomes alone and a disregard for the true impact of prospective deafblindness lead to delayed, unsuitable, and underfunded services. The individual and their family are then deprived of the support they need and deserve.

In high-income countries, such as Australia, children with Usher syndrome are likely to qualify for disability support (National Disability Insurance Scheme, 2024). However, in the early years, deafness is likely to be listed as the child’s primary disability rather than deafblindness. There is little to no agreement regarding when a deafblind individual is ‘deaf enough’ or ‘blind enough’ to warrant support. With support targeting either deafness or blindness and a lack of recognition of the true impact of dual sensory loss, the multiplicative impact of deafblindness is ignored.

Despite Usher syndrome being the cause of up to 6% of childhood hearing loss, (Delmaghani & El-Amraoui, 2022) service provision for people with this diagnosis remains inadequate. Due to the specialization of professionals in either vision or hearing loss, professionals are often ill-equipped to address the dual unique needs of those who are deafblind, hindering comprehensive service access and rehabilitation, resulting in a fragmented approach to care (Capella-McDonnall, 2005; Nelson & Bruce, 2016). This is exemplified in a series of interviews by Johansen et al. (2024) with the parent of a child with Usher syndrome summarizing: ‘They all do their own thing. So, the hearing people are over there, the visual people are over there, the vestibular physio is over there and none of them really talked to each other very much’ (p. 10). Integrated training and services are crucial for improved support for this unique population, ensuring that children with Usher syndrome receive comprehensive and coordinated care.

There can be substantial time pressure involved with several of the management strategies recommended following a diagnosis of Usher syndrome. For example, a diagnosis of Usher syndrome type 1 (born with profound deafness and vestibular dysfunction) may prompt earlier intervention and bilateral cochlear implantation, given the child is expected to develop worsening vision, with reliance on binaural sound localization (Ching & Leigh, 2020). Children with Usher syndrome type 2 (born with moderate to severe hearing loss) may gain benefit from early hearing aid implementation and audiological intervention (Castiglione & Möller, 2022). These intervention decisions can have a significant impact on child development, especially when made in the first few months of life, a time critical for language development.

Similarly, timely intervention for the visual system is vital. Once RP has been diagnosed, yearly eye checks are recommended with particular attention paid to contrast sensitivity, light sensitivity, and scotomas (or blind spots). This information can help schools and families determine optimal access in consideration of lighting and contrast. Individuals with RP are at increased risk of developing cataracts or cystoid macular oedema, which can impact central vision, but the impact can be minimized when treated early (Koenekoop et al., 2020; Nguyen et al., 2023). Awareness of future vision impairment can also significantly affect the choice of communication mode during the critical early years of life (Brodie et al., 2021).

Other critical interventions, such as vestibular rehabilitation, should also be implemented in the first few years of life for optimal results (Rine et al., 2004). It is known that children with Usher syndrome type 1 typically present with bilateral vestibular areflexia which can affect balance and result in gross motor delay (Castiglione & Möller, 2022). For those who have not received a genetic diagnosis, recognizing vestibular issues in a child can assist in finding the cause of their congenital deafness (Kletke et al., 2017). The first functional sign of Usher syndrome in a child with congenital severe profound deafness can be a delay in walking (at a mean age of 20 months) (Loundon et al., 2003). Vestibular hypofunction has been shown to identify progressive gross motor delay (especially in balance skills) in children with SNHL, requiring re-testing during preschool and early school years (Rine et al., 2000). In 3- to 8-year-olds, age-appropriate, child-friendly physiotherapy-guided exercises, including balance training (with visual and somatosensory focus), eye–hand coordination, visual motor training, and general coordination, have been shown to effectively reverse the progressive gross motor delay in children with bilateral vestibular dysfunction (Rine et al., 2004). In addition to training the use of somatosensory and visual inputs to compensate for vestibular loss, training which may differ in young children compared to adults (Rine, 2018), early intervention for children with Usher type 1 also involves making environmental adjustments, such as appropriate lighting, across the child’s environments (Castiglione & Möller, 2022), underscoring the need for prompt and specialized care.

The psychosocial impacts of Usher syndrome

The psychological impacts of a diagnosis of Usher syndrome are profound and significantly affect individuals and their families. (Dean et al., 2017; Högner, 2015; Johansen et al., 2024; Watters-Miles, 2014). This impact is intensified when Usher syndrome is underestimated or not fully understood. In adults, the psychological effects of Usher syndrome are well-documented (Arcous et al., 2020; Wahlqvist et al., 2020), including anticipatory grief and uncertainty about the future (Ellis & Hodges, 2013); heightened stress and anxiety (Ehn et al., 2018); disengagement with daily activities and the community (Roborel De Climens et al., 2020); and a cycle of grief and loss that significantly affects psychosocial development (Brown-Ogilvie, 2024).

Timely diagnosis may relieve emotional distress for parents of children with suspected Usher syndrome, providing clarity and direction (Johansen et al., 2024). However, it is important to understand that the impact will vary among individuals and families. For some, the family dynamic changes in response to seeking and utilizing resources to assist with the sensory diagnosis. For others, the additional information helps influence decision-making regarding hearing intervention and shapes expectations while providing explanations for the child’s clinical presentation (Alford et al., 2014; Moeller, 2000; Yoshinaga-Itano et al., 1998).

What remains clear is that there is limited evidence on the psychological impact of raising a child with Usher syndrome. More research is required on the psychological implications of an early diagnosis on the individual, caregivers, and the family unit, particularly before the onset of functional vision loss.

Conclusion

Usher syndrome presents unique challenges when accurately estimating the prevalence of childhood deafblindness and urges us to consider the inclusion of children with prospective deafblindness. The nature of Usher syndrome challenges estimates on methodological grounds, definitions of deafblindness, and requires support for families as they adapt to the progressive nature of this unique disability. Accurate and early identification, recognition, and support are critical for children with Usher syndrome. Understanding the risks of underrepresentation in the context of deafblindness is essential to ensuring that individuals with Usher syndrome and their families receive the necessary support, to address and mitigate the challenges they face.

The unique challenges posed by deafblindness require comprehensive, person-centred approaches that go beyond clinical management to address the emotional, social, and psychological needs of all affected. Acknowledging and understanding these complexities is essential for developing effective interventions and supports that enhance the quality of life for individuals with Usher syndrome and their families.