He Usher's syndrome Is constituted by a group of disorders of congenital hereditary origin characterized by neurosensorial alterations (Nàjera, Baneyto and Millán, 2005).
At the clinical level, this pathology is defined by the presence of bilateral deafness, retinitis pigmentosa and various vestibular alterations (Nàjera, Baneyto and Millán, 2005).
Depending on the severity and the affected areas, Usher's syndrome is usually divided into three clinical forms: Usher's syndrome I (USH1), Usher syndrome II (USH2) and Usher syndrome III (USH3) (Jaijo, Aller, Beneyto, Nájera and Millán, 2005).
The etiological cause of this syndrome is associated with an autosomal recessive pattern defined by a broad genetic heterogeneity (Dyce Gordon, Mapolón Arcedor, Santana Álvarez, 2011).
More than 8 different genes related to the onset of Usher's syndrome have been identified. These are responsible for each of the clinical subtypes (López, Gelvez and Tamayo, 2011).
The diagnosis of this disease requires the use of different ophthalmological and audiological analyzes. In addition, a genetic study is usually performed for the analysis of specific mutations (Sabaté Cintas, 2009).
There is no curative therapeutic approach to this disorder. The most common is to use methods of physical adaptation, rehabilitation, mentoring / mobility and special education (Sabaté Cintas, 2009).
In addition, the medical prognosis of those affected is usually characterized by the progressive development of psychiatric and / or neurological psychological alterations that will significantly impair their quality of life (Dyce Gordon, Mapolón Arcedor, Santana Álvarez, 2011 ).
Usher Syndrome Characteristics
Ushser syndrome (SU) is one of the most common causes of blindness and deafness of genetic origin (American Academy of Ophthalmology, 2013).
It is a disease characterized by the clinical presentation of auditory impairment of a sensorineural nature, loss of visual acuity and vestibular abnormalities (American Academy of Ophthalmology, 2013).
The clinical course is associated to (Nàjera, Baneyto and Millán, 2005):
- Injuries and abnormalities in the inner ear (impairment of hearing and balance).
- Retinitis pigmentosa (impaired vision)
This disorder is defined especially by its clinical and genetic variability. Clinical studies tend to use the term Usher Syndrome as a cluster of disorders (USH1, USH2 and USH3) (Genetics Home Reference, 2016).
It is a disease with a great medical and psychological interest, due to the degree of sensory and social incommunication that the affected people present (Jaijo et al., 2005).
The first clinical descriptions of this disorder are due to Von Graefe and Libreich, who identified a significant medical association between deafness and retinitis pigmentosa (Braga Norte, Cortez Juares, Nardi, Dell'Aringa and Kobari, 2007).
Its hereditary character is identified in 1914, thanks to the studies of the British ophthalmologist Usher, from whom it receives its name (Cleveland Clinic, 2016).
However, Bell (1933) was one of the pioneers in identifying the great clinical heterogeneity that defines this syndrome (Dyce Gordon, Mapolón Arcedor, Santana Álvarez, 2011).
About us
Most clinical, epidemiological and / or experimental studies consider Usher syndrome to be a rare or uncommon disease (Wallber, 2009).
However, Usher syndrome is the most common cause of deafblindness in humans (Wallber, 2009).
The origin of the clinical characteristics of 6% of congenital deaf individuals and 18% of those who suffer from congenital deafness Retinitis pigmentosa Are due to the condition of the Usher syndrome (Lopez, Gelvez and Tamayo, 2011).
The overall prevalence of this syndrome is estimated at approximately 3-4 cases per 100,000 people in the general population, if a specific association to gender, race or geographical origin (Sabaté Cintas, 2009).
However, other authors such as López, Gelvez and Tamayo (2011) place the prevalence in 3.5-6.2 cases per 100,000 people.
In the case of Spain, the prevalence figures can reach 4.2 cases per 100,000 inhabitants, assuming about 1,600 affected in all the territory (Jaijo, Aller, Beneyto, Nájera and Millán, 2005).
In the United States, this has been in about 5 cases per 100,000 inhabitants; In the Scandinavian regions at 3 per 100,000 and in Colombia at a figure close to 3.2 cases per 100,000 people (López, Gelvez and Tamayo, 2011).
Finally, regarding the distribution of cases by subtypes, we can point out the following data (Genetics Home Reference, 2016):
- Type I and II as the most common forms of Usher syndrome.
- Type III, the least common representing 2% of the total cases.
Signs and symptoms
The clinical characteristics of Usher's syndrome are related mainly to sensorineural deafness, loss of visual acuity and alteration of the vestibular system.
Sensorineural Deafness
The level of auditory acuity can vary considerably among those affected and depending on the subtype of Usher syndrome that is suffered (Sabaté Cintas, 2009).
Individuals may have total congenital deafness, moderate hearing problems, or normal or efficient acuity (Sabaté Cintas, 2009).
All the problems associated to the auditory area have their origin in the presence of a type of sensorineural alteration. Thus, the most common is to observe a type of sensorineural deafness or hearing loss (Genetics Home Reference, 2016).
This pathology refers to the presence of congenital lesions in the inner ear and a variable alteration of the fibers and nerve terminals associated with the auditory nerve (Cochlear, 2016).
Loss of Visual Acuity
Visual disturbances often constitute the basic clinical alteration of the Usher syndrome (American Academy of Ophthalmology, 2016).
The affected individuals present a course characterized by a progressive reduction of visual acuity, defined by the following pattern (Genetics Home Rrefernece, 2016):
- Loss of night vision.
- Loss of lateral vision.
- Emergence of blind spots.
- Development of opacity in the lens (cataracts).
All these ophthalmological abnormalities have their origin in the presentation of retinitis pigmentosa (RP).
Retinitis pigmentosa is a medical condition that refers to the progressive development of lesions in light-sensitive ocular cells (American Academy of Ophthalmology, 2016).
These cells, called cones and rods, are placed in the retina And are able to convert light stimuli into interpretable electrical signals at the brain level (American Academy of Ohthalmology, 2016).
The incidence of different factors, such as genetic abnormalities, can lead to the death of these cells (American Academy of Ophthalmology, 2016).
It initially affects rods, which are mainly responsible for nocturnal and peripheral vision. Later, there is a deterioration of cones, responsible for the central vision and the perception of colors (American Academy of Ohthalmology, 2016).
Vestibular System Alteration
Congenital anomalies present in the inner ear can also cause some significant alterations in the vestibular system (Nàjera, Baneyto and Millán, 2005).
The vestibular system consists of several structures that play a fundamental role in the balance and efficient maintenance of body posture.
This system groups several peripheral components (vestibular nerve terminals and inner ear) and others of character central character at cerebral and spinal level.
In Usher's syndrome, the involvement of any of these components will trigger various symptoms related essentially to balance (Genetics Home Reference, 2016).
As a consequence, it is common to observe problems of orientation, frequent loss of balance, acquisition of sedestation and delayed standing, among others (Genetics Home Reference, 2016).
What are the different subtypes?
Usher syndrome can be classified into several subtypes depending on the age of onset of the first symptoms, clinical characteristics and severity of the medical picture (Jaijo, Aller, Beneyto, Nájera and Millán, 2005).
Usher Syndrome Type I
The first subtype of Usher syndrome is possible to identify it from birth, although some of the specific characteristics are progressive (Sabaté Cintas, 2009):
Auditory abnormalities are characterized by the presence of a profound deafness of congenital nature, that is, from birth. In addition, it is not possible to use specific adaptations, such as hearing aids to improve this ability.
Visual disturbances have to appear insidious. Early vision problems occur around the age of 10 and can progress to blindness with increasing age.
It is also possible to identify anomalies related to the vestibular system. These are fundamentally through the serious problems of balance.
Usher Syndrome Type II
Usher syndrome II subtype presents a later debut. The typical ages of onset of the first symptoms are usually in the adolescent stage (Sabaté Cintas, 2009):
Hearing disorders are usually less serious. Although the development of moderate hearing deficits is possible, it is possible to wear hearing aids to improve their efficiency.
In addition, the presence of residual hearing allows them to use oral language as a fundamental means of communication.
Visual deficits have to be associated with the progressive development of retinitis pigmentosa, while the balance is not significantly affected.
Usher Syndrome Type III
The third and last subtype of Usher syndrome has a typical presentation during adulthood. Although some clinical features may be presented earlier (Sabaté Cintas, 2009):
Auditory acuity is characterized by a normal or standard onset that have to be reduced in adulthood, having deafness.
Visual abnormalities are defined by the presentation of adrenal retinitis pigmentosa and the development of blindness during the intermediate phases of the adult stage.
Finally, the vestibular system is also affected, leading to the development of important problems of coordination and balance.
Causes
As we pointed out in the initial description Usher's syndrome has an autosomal recessive hereditary origin (Lopez, Gelvez and Tamayo, 2011).
Genetic alterations are essentially defined by heterogeneity, since each of the different subtypes corresponds to different anomalies (López, Gelvez and Tamayo, 2011).
It has been possible to identify more than 12 sites of different genetic alterations, accompanied by more than 8 specific mutations: MYO7A, USH3, USH1C, VLGR1, CDH23, SANS, CLRN1, OCDH15 (Nàjera, Baneyto and Millán, 2005).
Most type I cases are associated with mutations of the MYO7A and CDH12 gene. While type II is more related to specific mutations in the USH2A gene. Finally, type III is due to mutations in the CLRN1 gene (Genetics Home Reference, 2016).
Diagnosis
The clinical features of Usher's syndrome derive their diagnosis towards an auditory, ophthalmological and vestibular system (American Academy of Ophthalmology, 2016).
Therefore, it is essential to evaluate the auditory capacity, the visual acuity and the presence of possible alterations of the balance and the coordination of body (American Academy of Ophtalmology, 2016).
- Auditory examination : Audiometry, otoacoustic emissions, cochlear evoked potentials and otoscopy (Sabaté Cintas, 2009).
- Ophthalmic examination : Eye fundus, campimetry, electroretinogram, electrooculogram and electronystagmogram.
- Vestibular exam : Although some of the previous tests may identify some alterations of the vestibular system, the most usual is to perform a balance test.
In addition to the approaches described above, it is vitally important to perform a genetic study because of the hereditary nature of this pathology.
The fundamental objective of this type of tests is to identify the specific genetic mutation that gives rise to the clinical subtype that the patient suffers and to identify its heritability pattern.
Treatment
There is no cure or therapeutic approach specifically designed for Usher's syndrome (Sabaté Cintas, 2009).
Different specialists and institutions, such as the American Academy of Ophthalmology (2016), point out that the best approach to health care is early identification and diagnosis.
Classical therapies include:
- Hearing compensation devices such as cochlear implants.
- Visual compensation devices, such as lenses or adaptations.
- Vitamin therapy based on the administration of Vitamin A For the control of retinitis pigmentosa.
- Physical rehabilitation for the improvement of the problems of balance and corporal coordination.
- Communication therapy for the generation of alternative forms of communication.
In addition, research is also underway on alternative therapies of the latest generation, all associated with genetic replacement.
References
- AAO. (2016). Diagnosis and Treatment of Usher Syndrome. Retrieved from the American Academy of Ophthalmology.
- Cleveland Clinic. (2016). Usher Syndrome. Retrieved from"Cleveland Clinic: Usher syndrome."
- Dyce Gordon, E., Mapolón Arcendor, Y., & Santana Álvarez, C. (2011). To medical, genetic and psychosocial aspects of the Usher syndrome.
- Jaijo, T., Aller, E., Beneyto, M., Nájera, C., & Millán, J. (2005). Molecular genetic study of Ushser's syndrome in Spain. Acta Otorrinolaringol Esp.
- López, G., Gelvez, N., & Tamayo, M. (2011). Frequency of mutations in the usherin gene (USH2A) in 26 Colombian individuals with Usher's syndrome, type II. Biomedical.
- Nájera, C., Beneyto, M., & Millán, J. (2005). Usher syndrome: an example of genetic heterogeneity. Med Clin Barc. Retrieved from Med Clin Barc.
- NIH. (2016). Usher syndrome. Retrieved from the Genetics Home Reference.
- NORD. (2016). Usher Syndrome. Retrieved from the National Organization for Rare Disorders.
- Sabaté Cintas, V. (2009). What is Usher Syndrome? MGF.