Usher syndrome exists in three types with type 1 patients being the most severely affected, whilst type 2 and 3 represent moderate and mild entities of this syndrome, respectively. Affected heterozygotic children are usually asymptomatic while homozygotes displaying a wide array of features present most often since birth.

A moderate to profound sensorineural hearing loss in both ears is seen at birth in homozygotic type 1 and type 2 patients. They may also concurrently develop speech deficits. Type 3 patients present with normal hearing at birth.

The sensorineural deafness is often diagnosed in isolation until the features of retinitis pigmentosa become apparent. Retinitis pigmentosa is initially marked by symmetrical and bilateral degeneration of the peripheral regions of the retina and later spreading to the more central regions [1]. Frequently, the initial symptoms noticed by the individual or his/her parents or teachers include night blindness and tunnel vision, with the constriction of visual fields continuing well into adulthood [2]. These features occur much earlier in type 1 patients than in the other types. Complete blindness may develop in these individuals.

Another important feature exclusive only to type 1 Usher syndrome patients is vestibular areflexia due to which walking milestones are achieved at a later date than usual (18 months to 2 years). Other children may appear clumsy whilst walking with frequent injuries being reported in these patients.

• Abnormal Eye Movement

  Stability when standing with eyes open and closed. Eye movements when following a target while wearing video goggles. Abnormal eye movements when lying down quickly on the couch. Abnormal eye movements when moving or shaking your head. [sense.org.uk]

• Hearing Impairment

  One individual (IV:1) is profoundly hearing impaired and has normal vestibular function and retinitis punctata albescens (RPA). [ncbi.nlm.nih.gov]

  HEARING IMPAIRMENT, and CORRECTION OF HEARING IMPAIRMENT by non-medical or non-surgical means. [bioportfolio.com]

  "We thought that the size of the DFNA9 patient population was unique, because hereditary hearing impairment is so heterogeneous. But now we have stumbled upon another form of dominant inherited hearing impairment: DFNA21. [radboudumc.nl]

• Onset at Age <20

  Families contained five living individuals and at least two living individuals with any type of rare inherited retinal or corneal disease with onset before age 20 years were eligible for the study. [bmcophthalmol.biomedcentral.com]

• Vertigo

  She did not complain of vertigo. The family history was unremarkable. Physical examination revealed no obvious abnormalities of the external ear or tympanic membrane. [e-ceo.org]

  Case 3 The patient was a 43-year-old female with a history of hypertension, hypothyroidism, sarcoidosis, gastritis, uveitis, and vertigo who presented with 2-year history of progressively worsening lower back pain radiating to both lower extremities. [cyberleninka.org]

  吉村 豪兼; 矢野 卓也; 内藤 武彦; 宮川 麻衣子; 茂木 英明; 西尾 信哉; 宇佐美 真一; めまいを主訴とした多発性硬化症の1例 Equilibrium research,70(4):245-249 2011(Aug. 01) Author:吉村 豪兼; 坂口 正範; 福岡 久邦; 塚田 景大; 宇佐美 真一; Abstract:A 27-year-old woman who was referred to our hospital 5 days after an episode of vertigo [soar-rd.shinshu-u.ac.jp]

  Vestibular function was considered normal in the presence of nystagmus associated with a sensation of vertigo. [bjo.bmj.com]

  However, another two probands clearly showed a vertigo symptom, supporting a type III diagnosis (Table 1). Among these patients, more severe visual dysfunction was present in the elders. [journals.plos.org]

• Dystonia

  Additionally, they exhibit varying degrees of balance issues due to mild to moderate vestibular dysfunction.[13] Differential Diagnosis Nonsyndromic Hearing Loss Deafness-Dystonia-Optic Neuronopathy Syndrome Alport Syndrome Bardet--Biedl Syndrome Alstrom [eyewiki.aao.org]

The diagnosis of Usher syndrome is primarily clinical and should be suspected in individuals who present with the clinical features as listed above amidst otherwise normal physical examination. These include sensorineural deafness, vestibular areflexia, and retinitis pigmentosa. A thorough assessment to detect the presence and severity of these conditions needs to be made via appropriate audiological, vestibular, and ophthalmologic evaluation. In addition, the presence of a family history of autosomal recessive diseases raises the likelihood of the presence of Usher syndrome in these individuals.

When the clinical features are inconclusive, molecular genetic testing techniques may be employed to reach a proper diagnosis. These may include serial single gene testing, multi-gene panels, or other extensive genomic tests to look for pathogenic variants of the related genes.

Single gene testing may involve the testing of genes such as the MY07A, USH1C, and CDH23 genes for type 1 patients. Testing for the USH2A, ADGRV1, and WHRN (DFNB31) genes may be required for type 2 patients [3] [4] [5]. Multi-gene panels may also be utilized to look for biallelic pathologic variants of the associated genes [6] [7] [8]. Other molecular techniques assessing the deletions and/or duplications of the genes may also be employed.

If the diagnosis is still uncertain, more comprehensive genomic tests (exome and full genome sequencing) may be carried out which may reveal mutations and diseases not included in the differential diagnosis previously.

Information about a therapy, service, product or treatment does not in any way endorse or support such therapy, service, product or treatment and is not intended to replace advice from your doctor or other registered health professional. [betterhealth.vic.gov.au]

“Today’s treatment for Usher syndrome is limited to cochlear implants or hearing aids, which help to address the hearing loss, but there is no biological treatment for HL and the blindness. [physician-news.umiamihealth.org]

While there are currently no universally agreed upon treatments for Usher syndrome, there are a number of treatments nearing clinical trial that could potentially help people with Usher syndrome. [usher-registry.org]

The best treatment, however, is early identification so that education programs can begin as soon as possible. [entcolumbia.org]

READ OUR CLINICAL TRIALS GUIDE Existing Treatments and Standard of Care Currently, there is no treatment or cure for Usher syndrome. [fightingblindness.ca]

Diagnosis and Prognosis: Auditory testing can detect deafness at birth but this is often missed in the absence of a family history. [disorders.eyes.arizona.edu]

Because of the poor visual prognosis, the patient refused surgery in that eye. Tractional retinal detachment should be added to the differential diagnoses of visual loss in patients with retinitis pigmentosa. [ncbi.nlm.nih.gov]

Furthermore, the authors compare their psychiatric symptoms with other reports and the possible etiologies of psychotic symptoms are discussed. [ncbi.nlm.nih.gov]

Our understanding of, and ability to test for, the underlying etiology of syndromes has been greatly enhanced by the study of the human genome and proteins necessary for normal development. [asha.org]

These results suggest that our panel is an effective approach for the genetic diagnosis of Usher syndrome leading to: 1) an accurate molecular diagnosis, 2) better genetic counselling, 3) more precise molecular epidemiology data fundamental for future [ncbi.nlm.nih.gov]

Epidemiology The incidence is about 1 in 25,000. About 3-6% of hearing impaired children have the condition. Types 1 and 2 are more common than type 3 and together account for 90-95% of Usher's syndrome and about 10% of all children born deaf. [patient.info]

This was possibly thanks to the epidemiological surveillance practiced in communities to control vector transmission, allied with the National Program for Chagas Disease Control and rural socioeconomic factors. [htct.com.br]

USH1G, USH1H, USH1J, USH1K Usher Syndrome II Loci: USH2A, USH2C, USH2D Usher Syndrome III Loci: USH3A In general, genes associated with Usher syndrome provide instructions for the synthesis of proteins involved in normal hearing, balance, and vision.[3] Epidemiology [eyewiki.aao.org]

The identification of pathogenic mutations is of great significance for elucidating the underlying pathophysiology of USH. [ncbi.nlm.nih.gov]

"Thus, we provide the first evidence that splicing dysregulation may participate in the pathophysiology of Usher syndrome," is how the authors sum up their results in their article. [uni-mainz.de]

It has been shown that Type III occurs more frequently in the Finnish population.[9] Pathophysiology Hearing loss is due to a defect in the inner ear hair cells. [eyewiki.aao.org]

[…] ush2armc zebrafish model, which revealed similar changes in photopigment mislocalisation with elevated autophagy levels at 6 days post fertilisation indicating a more severe genotype-phenotype correlation, and providing evidence of new insights into the pathophysiology [academic.oup.com]

[…] deposits at the dermoepidermal junction For a thorough description and introduction to the possible causes of pemphigus, see the article " Pemphigus: An Acronym for a Disease with Multiple Causes ", published by the International Pemphigus Society. [2] Pathophysiology [emedicine.medscape.com]

Prevention Can Usher syndrome be prevented? Usher syndrome occurs because of the genes you inherit. At this time, there is no way to prevent it. Genetic testing can determine if you and your partner both carry the gene. [my.clevelandclinic.org]

A variety of different viral-based delivery approaches have been tested for retinal gene therapy to prevent the blindness of Usher 1B, and a clinical trial based on one of these approaches has begun. This review evaluates the different approaches. [ncbi.nlm.nih.gov]

Folic acid taken before conception, and during at least the first four weeks of pregnancy, can prevent around seven out of 10 cases of neural tube defects. [betterhealth.vic.gov.au]

Foundation Fighting Blindness homepage The urgent mission of the Foundation Fighting Blindness is to drive the research that will provide preventions, treatments and cures for people affected by retinitis pigmentosa, macular degeneration, Usher syndrome [fightingblindness.org]

1. Gregory-Evans K, Bhattacharya SS. Genetic blindness: current concepts in the pathogenesis of human outer retinal dystrophies. Trends Genet. 1998;14(3):103-108.
2. Pennings RJE, Huygen PLM, Orten DJ, et al. Evaluation of visual impairment in Usher syndrome 1b and Usher syndrome 2a. Acta Ophthalmol Scand. 2004;82(2):131-139.
3. Bonnet C, Grati M ’Hamed, Marlin S, et al. Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis. Orphanet J Rare Dis. 2011;6:21.
4. Le Quesne Stabej P, Saihan Z, Rangesh N, et al. Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study. J Med Genet. 2012;49(1):27-36.
5. García-García G, Besnard T, Baux D, et al. The contribution of GPR98 and DFNB31 genes to a Spanish Usher syndrome type 2 cohort. Mol Vis. 2013;19:367-373.
6. Hilgert N, Kahrizi K, Dieltjens N, et al. A large deletion in GPR98 causes type IIC Usher syndrome in male and female members of an Iranian family. J Med Genet. 2009;46(4):272-276.
7. Besnard T, Vaché C, Baux D, et al. Non-USH2A mutations in USH2 patients. Hum Mutat. 2012;33(3):504-510.
8. Aparisi MJ, Aller E, Fuster-García C, et al. Targeted next generation sequencing for molecular diagnosis of Usher syndrome. Orphanet J Rare Dis. 2014;9:168.