La ataxia espinocerebelosa tipo 2 (SCA2) es una enfermedad genética con Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant. Spinocerebellar ataxia type 7 (SCA7), currently the only known form of autosomal characterized by progressive ataxia, motor system abnormalities, dysarthria. Infantile-onset spinocerebellar ataxia (IOSCA) is a hereditary neurological disorder with early and severe involvement of both the peripheral and central nervous.
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Hereditary Ataxia Overview – GeneReviews® – NCBI Bookshelf
The spinocerebellar ataxias SCAs are a group of neurodegenerative diseases that have a genetic origin. Some are caused by a mutation in a gene that lead to the production of an abnormal protein called ataxin, a transcription factor that tends to form inclusions in the nucleus and cytoplasm of the cell. Espinocreebelosa alteration has been associated with the clinical and pathological manifestations of this disease.
However, little is known about these diseases in many Latin American ataxla. The purpose of this review is to present the current state of research on SCAs, its classification, and to describe a Mexican family diagnosed with SCA type 7 SCA7to understand its history and genealogy. Because it is important to describe the prevalence and frequencies of the SCAs in other states of Mexico, it is necessary to support research in this area, especially in government health institutions.
Ataxia espinocerebelosa, Enfermedad neurodegenerativa, Tripletes repetidos, Ataxina. Neurodegenerative diseases represent a large group of disorders of the central nervous system CNS. Esplnocerebelosa the clinical and neuropathological characteristics of the various neurodegenerative diseases differ, they share the symptoms taaxia neuronal degeneration, and the subsequent functional impairment of the affected areas.
Ataxia derives from the Greek word “a-taxis”, which means espinoverebelosa order”. It is also used to describe a gait disorder, “drunk walk”, which is characterized by instability, lack of coordination, and increased base of support. However, these characteristics can vary even among members of the same family. As such, the classification needs to be determined by biochemical and molecular procedures that are focused on the involved genes.
The purpose of this review is to present the current state of research on the SCAs espinocdrebelosa its classification, and to describe a Mexican family diagnosed with the SCA7, to understand its history and genealogy. T his group includes neurodegenerative disorders characterized espinocerebeloda a slowly evolving degeneration of cerebellar neurons espinocerrbelosa other different neural structures, including the spinal cord and basal ganglia.
When this transcript is translated into protein, there are repetitions of the corresponding amino acid, and the mutated protein tends to aggregate within nuclear inclusions. The pioneering work of Harding in the early s initiated the clinical-genetic classification of this disorder, leading to the more recent classification based on molecular genetics.
The inherited ataxias are classified according to the specific genetic deficit, including autosomal dominant, autosomal recessive, mitochondrial diseases and X-linked ataxias. For most ataxia cases, it is possible to characterize the molecular genetic defect that causes the disease. I n ADCA Figure 1the gene causing the disease is found on a non-sex chromosome and, accordingly, affects women and men equally. Schematic illustrating rspinocerebelosa dominant inheritance.
The affected parent has a defective allele Dwhich dominates its normal counterpart n. Different ataxiw mechanisms for autosomal dominant disorders have been identified. The name SCA24 was assigned to the single recessive form of spinocerebellar ataxia, 10 and dentatorubral-pallidoluysian atrophy DRPLA is included in this group. All available evidence suggests that these disorders are caused by the abnormal function of a protein called “ataxin” e.
In another group of dominant disorders, including episodic ataxias 1 to 7 EA 8 and SCA6 Table 1the mutations affect genes that encode ion channels. Diseases with an autosomal recessive inheritance pattern are generally rare, and their inheritance follows the expected Mendelian ratio of 3: Unlike dominantly inherited diseases, diseases with autosomal recessive inheritance require two copies of the defective gene for a person suffer the symptoms of the disease Figure 2.
Schematic illustrating autosomal recessive inheritance. Both parents who usually do not have the rspinocerebelosa, carry a espinocerebelsa dominant allele Nwhich takes precedence over its defective and recessive counterpart r.
The autosomal recessive ataxias Table 2 are caused by the loss of a mitochondrial protein, frataxin, which has been linked to respiratory function and iron homeostasis. However, for reasons that remain unclear, the symptoms are not necessarily present at birth or during infancy. List of autosomal dominant cerebellar ataxias and their mutations. A mutation located on chromosome 11pq Ataxia described in the ancestors of U. The expansion of CAG trinucleotide on chromosome 3p List of autosomal recessive cerebellar ataxias and their defects.
Mitochondrial diseases are due to a mutation in the mitochondrial genes that are responsible for energy production. The characteristic symptom of these mitochondrial disorders is ataxic gait, and is ataxis associated with other complications such as peripheral neuropathy, ophthalmoparesis, retinitis pigmentosa, etc.
X-linked ataxia is a disorder that affects men in one or more generations in the maternal line, and espinocereebelosa ataxia is among the most common disorders observed Table 3.
The symptoms that occur most frequently include: This group includes sporadic or acquired ataxias, which may be caused by chronic alcoholism, toxins espinocwrebelosa drugs phenytoin, lithium, valproate, amiodarone, metronidazole, procainamide, mefloquine, isoniazida, metals espinocerebelossa solventshypothyroidism, stroke, infectious diseases, and neoplastic disorders. Approximately 15 years ago, it was discovered that many neurodegenerative diseases are attributable to increases in unstable triplet repeats in DNA.
To date, more than 35 SCAs have been described, and, in at least seven of these diseases, the repeated element is a CAG triplet coding for glutamine. Many diseases have been described to result from the formation of polyglutamine repeats.
List of espinocerrebelosa diseases and X-linked ataxias. atacia
Orphanet: Ataxia espinocerebelosa tipo 7
Multiple proteins contain areas of polyglutamine residues polyQ that are prone to instability and expansion. Up to a certain length, the occurrence of polyQ in the ataxin protein is not pathogenic.
However, larger expansions can cause the symptoms that are characteristic of neurodegenerative disease. In the case of ataxin-7, 4 to 17 CAG repeats are considered to be in the normal espinoerebelosa, with 10 being the most frequently observed number of repeats.
Treatment of the SCAs. In general, treatments for neurodegenerative diseases are lacking, and therapeutic interventions, mostly comprise symptomatic and palliative measures. Neurodegenerative diseases constitute a terrible disability, and can cause physical and psychological suffering in patients and their families. Currently, there is no cure for spinocerebellar ataxias, and preclinical and clinical studies with insulin-like growth factor-I IGF-I are ongoing. The serum levels of IGF-I are altered in animal models of ataxia and human patients, 29 but relationship between these altered levels and disease pathology is unclear.
Nevertheless, this relationship may be a target for the pharmacological treatment of ataxia. However, the mechanism by which these effects are mediated is unknown. The existence of this disease in Mexico was first reported by Matsuura et al. SCA10 is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. InRasmussen et al. They described the molecular findings in these patients, and reported an expansion of ATTCT repeats ranging from to repeats, with an average age at onset of The clinical signs were more significant, and included pan cerebellar ataxia and seizures.
Thus, SCA10 may affect tissues other than the cerebellum.
InAlonso et al. The distribution of ADCA was They identified six individuals with the rare allele CAG 33, and two with early onset ataxia.
These results showed the existence of different SCA in Espinocerebeloaa, and suggested the need for designing testing strategies for the general Mexican population. In other countries, however, research in the field of spinocerebellar ataxias has been ongoing for decades.
The reason for the delay in Mexico espincerebelosa be the lack of knowledge of the clinical and pathological features of the disease. T he family physicians or physical therapists who frequently examine people with any type of motor disorder may be unaware that they are observing a case of spinocerebellar ataxia. Additionally, patients may be dying of other complications without having been diagnosed with SCA. The IRAM is a civil association that was founded in by a family with a number of suspected cases of ataxias and whom adequate management was not provided by any hospital in the state.
However, much remains to be done by the Institutes and Health Center in terms of the detection and referral of individuals who have the classic symptoms of ataxia. No records exist in other hospitals for hereditary ataxias, and there is a lack of institutions specializing in the monitoring and care of patients with these neurodegenerative diseases.
It is of particular interest to focus on cases of SCA7, which have been detected in some states of Mexico, although SCA7 is also present in other countries. Spinocerebellar ataxia type 7.
SCA7 is an autosomal dominant cerebellar ataxia that is associated with progressive macular degeneration. It was formerly known as olivopontocerebellar atrophy type III 13 and is now known as spinocerebellar ataxia type 7.
Many families around the world and from different ethnic groups have been reported to have SCA7. SCA7 is characterized by progressive cerebellar ataxia; ophthalmoplegia; dysarthria; dysphagia; decreased movements saccades and visual acuity; pyramidal and extrapyramidal signs; deep sensory loss; and in some cases, symptoms of dementia.
The neuropathological features that have been reported to accompany SCA7 include a moderate to severe loss of neurons PkC and granule cells and gliosis in the cerebellum, 46 inferior olive, dentate nuclei, pontine nuclei and structures related to the motor system such as globus pallidus, substantia nigra, subthalamic nuclei, red nuclei and spinal cord. Genetic anticipation is often observed in SCA7, as is the case for the rest of the autosomal dominant cerebellar ataxias and in other diseases produced by CAG repeats.
Specifically, the number of repeats present is inversely proportional to the age of onset of symptoms and to the intensity of clinical involvement. InRolon-Lacarriere et al. The clinical history of the individual was obtained, and a neurological exam, including neuropsychological studies, neurophysiologic, ophthalmologic, neuroradiologic, and genetic tests was conducted.
In all members of the last generation, the observed symptoms included global cerebellar syndrome, pyramidal, visual impairment and varying degrees of ophthalmoparesis, maculopathy with progressive retinal degeneration, and atrophy of the cerebellum, brainstem and the cerebral hemispheres. Clinical anticipation was observed in three subjects, in whom the symptoms were more severe, and onset was earlier in the youngest generation.
Clinical and genetic studies showed that the disease was spinocerebellar ataxia type 7, and this was the first publication of SCA7 in a Mexican family. Here, we present the case of a family in Xalapa, which comprises peoples across five generations. A genealogical tree was constructed and was divided into three subfamilies Figures 3 A, B, C for clarity. The man in the first generation in the three subfamilies is the same and is thougth to be the index carrier of the mutation.
Subfamily A is composed of 29 individuals distributed into five generations, including 14 males Subfamily B is composed of 43 individuals distributed into four generations, with 26 males According to the data provided by family members and the IRAM files, 12 individuals might have been affected, of whom five had already died. These women had the characteristic expansion of triplets on chromosome 3p that was associated with retinal lesions, leading to diagnosis of spinocerebellar ataxia type 7.
This was the first report of SCA7 in the state of Veracruz. In da Cunha et al. One member of subfamily B II, 2 and one of the subfamily C IV,20 who were suspected to have the disease were not married and had no offspring. Similarly, the three women with genetic confirmation of SCA7 had no children, which contributed to the low incidence of cases in these subfamilies.