Swelling Of Foot After Pedicure

genetic diseases caused by mutation in the genes are presented with a very low frequency (4), but they are responsible for inherited conditions that usually affect significantly the quality of life of patients. They also have a considerable impact at the household, not only by the level disabling, but the anxiety that leads transmit to future generations.

The Korea or Huntington disease (HD), also known as Mal de San Vito, is an example of these hereditary diseases. Was recognized in 1872 by the American physician George Huntington Summer (4,5,8), based on a study of a mother and daughter who had choreic movements, progressive mental deterioration and suicidal tendencies (4). Huntington's Disease is not the only existing hereditary chorea (8), so the only way to make a definitive diagnosis is by a karyotype.

patient with Huntington's Disease Taken from youtube.com

http://www.youtube.com/watch?v=OveGZdZ_sVs

The prevalence is estimated between 5 and 10 people affected per 100,000 inhabitants, among populations EuropaOccidental and descendants (10). Not enough data to estimate the incidence in Costa Rica (10), however, they have been conducted that have confirmed certain hereditary characteristics of the disease (10). For 2007, it had conducted tests of 38 Costa Rican belonging to 4 different families. Of these individuals, 7 had a clinical diagnosis of HD and 18 had the characteristic mutation Huntingtons (10).



Etiology Genetic diseases are caused by mutations that can occur at the level of the genome, chromosome or genes (4). They are the result of imperfections that occur by chance in the DNA replication process or because of the physical or chemical agents (6). The level of gene mutation occurs with a very low frequency (4), however, there are cases where the injury is not resolved genes and thus is transmitted to the next generation.

The mutational mechanism responsible for Huntington's disease is known as trinucleotide repeat expansion (4). There is evidence that originates along the mitotic divisions of germ cells (4) (gametes). The mutation is unstable (4.6), which means that the size of the repeated sequence varies when cells divide (10).

In the case of Huntington, the trinucleotide CAG (cytosine-adenine-guanine) (4.10) is repeated over 36 times in a gene called HD10 or IT15. This gene is located on the short arm of chromosome 4 (4p16.3) and is responsible for producing a protein called huntingtin (htt) (4.10). The function is still unknown (4), but is highly expressed in the brain, mainly in the cytoplasm (4,10). The mechanism causing expansion and the way that leads to neurodegeneration is one of the many aspects of the htt protein has not been explained so far (4,10).

Figure # 1
Scheme with the location of the HD gene
Taken from Genetics Home Reference
http://ghr.nlm.nih.gov/gene=htt

mutant htt protein is completely dominant (4) and given that the affected chromosome belongs to the autosomes (sex chromosomes), it is said that this disease has an autosomal dominant inheritance pattern (4,6,10).

All individuals inherit the mutated allele will eventually develop the disease unless they die of other causes before the onset of symptoms (10).

The number of repeats influences the degree of neuronal degeneration and the age at which symptoms begin to manifest. A normal person is between 6 and 36 repeats (4.10). The greater the number of repetitions, the greater the degree of injury observed in the striatum (4).

The age of onset is inversely proportional to the number of CAG repeats (4,10). The more repetitions of the trinucleotide chain are present, the age of onset is lower. This pattern was confirmed in study in Costa Rica (10).

expansions between 40 and 50 CAG repeats are often seen in people with symptoms between 30 and 50. Juvenile HD is associated with cases that exceed the 70 repetitions (10). Unfortunately, current knowledge of Huntington's disease can not yet accurately predict when the symptoms will appear (10).

Another pattern that is currently studying the relationship between the parent inheriting the mutated gene and the number of CAG trinucleotide repeats. When the transmission is matrilineal, the allele is of equal or smaller size (fewer repetitions). When paternal transmission is the mutation in the child tends to be larger (more repeats) (4:10).

Detection of carriers of the disease in presymptomatic phases is now possible by molecular biology techniques (4). Although there are certain legal and ethical use of genetic counseling in these cases, it should be noted that enables parents to calculate the probability of having a son or daughter who will develop HD. Pathology



Although the mutant protein found in many places along the Centra Nervous System (l, 4), neurodegeneration appears specifically in the striatum (1,4,5,8,10 ) and cerebral cortex (l, 4,10,11). The reason why the injuries were concentrated in these areas is unknown (4).

The Corpus striatum is part of the basal ganglia, which are a group of interconnected gray mass nuclei involved in motor functions and non-motor (1). Found in the deep white matter of each cerebral hemisphere. Some texts refer to as the basal ganglia, however that term is not used by most neuroscientists (9).

The basal ganglia are mainly associated with the beginning and end of voluntary and involuntary movements (9), and the control of the adjustments required by them (11).
no motor function of the basal ganglia is related to cognitive processes and emotion (1). The lesions in these nuclei produce movement disorders such as chorea, athetosis, ballism, dystonia and tics. Note the difference with lesions in the cerebral cortex that usually cause total loss of movement (1).

The Corpus striatum consists of three cores called: caudate, putamen and globus pallidus (1.9).

Figure # 2
Scheme with the location of the basal ganglia
IMBIOMED Taken
http://www.imbiomed.com.mx

the caudate nucleus is a C-shaped structure that is higher than the thalamus. Has three parts: head, body and tail (1). The head of the caudate nucleus is in contact with one wall of the lateral ventricle.

is associated with the limbic system (9), especially anteriorly. For this reason it is said that is related to emotions such as anger, pleasure, docility and affection (9). Some studies indicate that the activity of neurons in this nucleus can be seen by eye movements (9) and is also associated with cognitive processes processes (11).

the putamen and globus pallidus are lateral thalamus and separated from it by the internal capsule. The putamen is closer to the cortex while the globus pallidus is deeper. The activity of neurons in the putamen preceding body movements (9), especially arms, legs and face. The globus pallidus is involved in the regulation of muscle tone in certain movements. These two nodes form a structure known as lenticular nucleus.

In advanced stages of Huntington's disease shows dilatation of the frontal horns of the lateral ventricles and the ventricles characteristic Wagon (4) (atrophy of the caudate head). Also observed retraction of dendrites, predominantly in the cerebral cortex (l, 4). While in the basal ganglia atrophy explains the movement disorders, the lesion in the cerebral cortex to an explanation of psychiatric problems, including dementia. Associated progressive personality changes (5).

Figure # 3

HD Impact (above) in the basal ganglia vrs normal brain (bottom)
Taken from Folding @ home
http://folding.stanford. edu / Inglés / FAQ-Diseases

The rest of the basal ganglia (Claustrum (2), amygdaloid nuclei, Subthalamic nucleus, substantia nigra and red) do not seem to be affected by Huntington's Disease, however it is related to other diseases where there are movement disorders such as Parkinson's (1). Pathophysiology



As mentioned above, the CAG trinucleotide expansion leads to the emergence of mutant htt protein with an abnormal aggregation capacity is directly proportional to the number of repetitions (4). The presence of this mutated protein and subsequently alter the dendrite neuronal death occurs by apoptosis (4). There is evidence of neuronal dysfunction in the body initially Striatum. In advanced stages of the disease is found atrophy, especially in the putamen (4).

Figure # 4
gliosis in the striatum, patients with HD (left) vrs. normal (right) Taken
Neuropathology
http://neuropathology.neoucom.edu/chapter9/chapter9eHD.html

pathological lesions are also characterized by proliferation of astrocytes in the central nervous system (gliosis .) Some authors specifically mention the process of reactive astrocytosis (4). Astrocytes are the largest cells of the neuroglia (1) (CNS supporting cells). It is thought that these cells are related to the healing of damaged tissue (1).

Physical and Psychological Symptoms

Huntington's disease, cognitive and psychiatric disorders tend to occur months or years before the other (4.5). Studies have explored the possibility of detecting neuropiscológico deficit when the patient is still pre-symptomatic (5), however it is difficult to make a proper diagnosis only with psychological tests.

The framework of cognitive and psychiatric disorders is variable (4.5), and ranges from subtle changes in personality to psychotic disorders (4). The literature review cites the following signs:

- Depression (4.8)
- Irritability (4.8)
- Reduced memory (4,5,10)
- Loss of self-criticism (4)
- Distractibility (3 , 4)
- mood changes (4.5)
- Anxiety (4)
- Apathy (4)
- Aggression (4)
- Insomnia (3.4)
- Hallucinations (4)
- suicidality ( 4)

Dementia is progressive (4,5,8,11) and ends up being global in advanced stages (4.5) and is established which is of subcortical type (3,4,5). This type is characterized by disturbances in the ascending reticular activating system (3), which is responsible for controlling the states of arousal, alertness and attention (1) and has a central role in the selective recognition (1). These features explain the distractibility, insomnia, and to some extent cognitive problems (1.3).

studies in this type of dementia indicate that the patient has difficulty initiating the process of attention and easily distracted (3). The answers may be successful but require a lot of time to produce (3).

physical manifestations are characterized by choreic hyperkinesias (1,4,8,10). Chorea is a movement disorder where there are sudden jerky, fast, frequent and involuntary (1,4,5,10), in the case of HD, the movements are messy, arrhythmic, and messy (4) in the extremities and trunk. The literature review cites the following signs:

- choreic movements of the limbs (1,4,8,10)
- Head Spins (1.4)
- protrusion of the tongue (4)
- Gesturing face (grimacing) (1,4,10)
- Lift Shoulders (4)

minor motor abnormalities include:

- Restless (4)
- eye movements (4)
- Nystagmus (4)
- hyperreflexia (4)
- Dysarthria (4.5)
- Dysphagia (4)
- Athetosis (4.11)
- rapid and excessive movements of the fingers (4) Diagnosis and

prodnóstico

Clinical diagnosis is based on the presence of a positive family history and testing of transmission of the disease in heritable (4). The installation of a progressive motor disability, mental disorders and neuroimaging (4).

Figure # 5

HD patient with magnetic resonance (top) vrs. normal subject (bottom)
scielo.br Taken
http://www.scielo.br/img/revistas/bjmbr/v39n8/html/6233i01.htm

In some cases it is possible to detect subtle alterations in cognitive and motor (4), however, definitive diagnosis can only be done by genetic testing (4).

When genealogical research is positive, the differential diagnosis must be made to:

Sydenham's chorea: a benign (1.4), there is atrophy of the caudate nucleus (4) and is caused by rheumatic fever (1). Is rapidly evolving. Vascular

Korea: filed at a later age and there is no hereditary factor (4). No psychiatric accented (4). Tendency to spontaneous improvement (4).

Infectious Koreas, caused by measles, smallpox, typhoid fever. Have an abrupt onset and gradual evolution is often localized and the absence of mental disorders (4). Koreas

Tumor: No heredity and mental disorders in the early stages (4). Their evolution is rapid and localized (4).

Wilson's disease: is presented at an earlier age, no dementia, presence of liver disease (4).

choreic syndrome secondary to injury: Outcome of trauma or drug ingestion, hyperthyroidism, stroke or encephalitis (4)

In advanced stages, patients lose their physical capacity mental and personal care. The march is difficult and swallowing problems (4). Death occurs pro complications from general weakness (4), usually between 10 and 25 years have shown the first symptoms (4). Patients do not die of Huntington's disease, died with the disease.

Treatment and Genetic Counseling

The current treatment of this disease is limited to alleviating some of the expressions (4). It is not possible to delay the onset or progression of symptoms (4). Usually provides support to paciete and their families (4). It seeks the participation of doctors, psychologists and therapists, especially to help the understanding of neuropsychiatric symptoms and offer a better quality of life for the patient (4).

Certain drugs used to treat dementia may be useful (4,7), yet none of them are considered truly effective for efficient treatment or other mental disorders.

From the point of view of genetic counseling, it is now possible to detect carriers of the disease (4). Even in Costa Rica is possible to perform these tests (10). Although the application of these techniques still has certain legal and ethical (4), have the advantage that help ease the anticipation and uncertainty, especially for people who want to know if the children are at risk of developing the disease (4).

Prenatal diagnosis is very controversial especially in countries where sex-selective abortion (4). Some scientists have found cases where some family members prefer not to know their carrier status (4).

In the study conducted in Costa Rica (10), participants were given continuous support during the process of deciding whether or not undergoing genetic testing, whether or not to know the outcome. Some of the positive cases are being followed by neurologists and psychologists. Original Paper



This research was part of Neuroanatomy course at American University. made by Katherine Chacón, Montserrat Alvarado, Karla Camacho, Angelica Garita and Leo Melendez.

Disposible online:
http://www.bluejaygallery.com/download/EnfermedadHuntington.pdf



References (1) Afifi, Adel. Ronald Bergman. 2006. Functional Neuroanatomy. 2nd. Edition. Editorial McGrawHill. Mexico. Cap 13.

(2) Crick, Francis. Kosh, Christof. 2005. What is the function of the claustrum?. Philosofical Transactions. (2005) 360, 1271-1279.

(3) Coello, Ramiro. Garcia, Angel. Nunez, Maria Isabel. 1980. A Case of Functional subcortical dementia. Honduran Medical Journal. Vol 48.

(4) Encinosa, Guianeya. 2001. Huntington's chorea. Journal of Human Genetics. Volume 3, Number 1. `

(5) Gadea, Marlen. Espert, R. Chirivella, Javier. 1996. Presymptomatic detection of neuropsychological deficits in Huntington disease: controversies. Behavioral Psychology. Volume 4, Issue 3. 363-375.

(6) Jaramillo, Juan. 2003. What the doctor should know about genes. Acta Médica Costarricense. College of Physicians and Surgeons. Volume 45, Number I.

(7) Jimenez, F. Toledo, M. Puertas, I. Lefty B. Barcenilla, B. 2002. Olanzapine improves chorea in Huntington disease patients. Journal of Neurology. 35 (6). 524-525.

(8) Royuela, A. Gil, A. Macías, 2003. J. A case of obsessive Symptoms in Huntington's disease. Actas Esp Psiquiatr. 2003, 31 (6). 367-370.

(9) Tortora, Gerald. Derrickson, Bryan. 2006. Principles of Anatomy and Physiology. 11 th. Edition. Editorial Médica Panamericana. Mexico DF. Mexico. Cap 14.

(10) Vasquez, Melissa. Morales, Fernando. Fernandez, Hubert. Del Valle, Gerardo. Fornaguera, Jaime. Cuenca, Patricia. 2007. Molecular diagnosis of Huntington's disease in Costa Rica. Acta Médica Costarricense. College of Physicians and Surgeons. Volume 50, Number I.

(11) Young, Paul. 2001. Clinical Functional Neuroanatomy. First Edition. Editorial Masson. Spain. Chapter 8.