ABSTRACT
Las distrofinopatías son un grupo de enfermedades ligadas al cromosoma X que abarcan diferentes entidades, siendo las más importantes la distrofia muscular de Duchenne (DMD) y la de Becker (DMB). Están causadas por mutaciones en el gen de la distrofina (gen DMD) localizado en el cromosoma X, locus Xp21.1. En relación con el tipo de mutaciones reportadas en el gen DMD, las delecciones y las mutaciones puntuales son las más comunes, mientras que las duplicaciones corresponden a 10-12%. Aunque las duplicaciones que abarcan el exón 5 ya han sido reportadas en la literatura, a la fecha no existen informes de casos que establezcan una relación genotipo fenotipo clara. Presentamos el caso de un paciente con distrofia muscular de Becker con un fenotipo no tan severo, en quien se encontró una duplicación en el exón 5. Con este caso pretendemos profundizar en la relación genotipo-fenotipo de la DMB, reportando las características clínicas en relación con la duplicación del exón 5 encontrada.
The dystrophinopathies are a group of X-linked genetic disorders. The most important forms of dystrophinopathies are Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). They are caused by mutations of the dystrophin-encoding DMD gene located on the X chromosome at Xp21.1. Among the type of gene DMD mutations reported, deletions and point mutations are the most common, while duplications occur in 10-12% of cases. Although duplications of exon 5 are already reported in the literature, to date there are no cases reported which establish a clear genotype-phenotype correlation. Here we present the case of a patient with Becker muscular dystrophy with a slightly milder phenotype, in whom exon 5 duplication was found. With this case report, we intend to highlight BMD genotype-phenotype correlation by describing BMD clinical features in relation with exon 5 duplication.
Subject(s)
Humans , Male , Adolescent , Muscular Dystrophies , Muscular Dystrophy, Duchenne , X-Linked Emery-Dreifuss Muscular DystrophyABSTRACT
Summary: The obstructive sleep apnea syndrome (OSAS) is a type of sleep disorder that has called the attention of many researchers because of its widespread distribution among middle-aged subjects. The OSAS is a respiratory problem characterized by the existence of apneas, defined as 10 second minimum intervals during which no aerial flux exchange takes place through the upper airways and the hypopneas not characterized by an arrest, but by a reduction of aerial flux through the upper airways. The most widespread index used in the diagnosis of the OSAS severity has been the apnea/hypopnea index (AHI). There is little consensus based on the apnea/hypopnea index regarding the clinical definition of the sleep apnea syndrome, as there is not a single criterion for the categorization of sleep apnea patients into severity levels. Nowadays, it is estimated that about 70% of the patients referred to sleep laboratories suffer from snoring, and it is suspected that they might also suffer from sleep apnea. Obstructive sleep apnea patients may suffer from memory and cognitive problems, excessive daytime sleepiness, as well as mood disturbance, among other symptoms. Additionally, this disorder has severe medical and social consequences. One of the most characteristic symptoms in sleep apnea is snoring. Although snoring is one of the symptoms of sleep apnea, it should be remembered it is a typical phenomenon among population in general. There is a primary kind of snoring, the most frequent type in less severe cases, which even occurs among the normal population. In this case, the noise accompanying inspiration is made with almost every breath. Secondly, there is another kind of snoring that is either intermittent or cyclic, and snoring does not come with every breath but silent periods are also frequent. The latter indicates apnea. A considerable number of epidemiological studies regarding snoring have been produced of late. Several of them have concluded that snoring may have severe clinical consequences. Most patients suffering from obstructive sleep apnea start having simple snores. In the last decade there has been a marked increase of patients who manifest respiratory disorders related to sleep who do not fall into the category of apnea patients. Nevertheless, the morbidity of these clinical disorders is not yet known, a circumstance that makes treatment more difficult. Only a reduced number of studies have tried to find out whether snorers show any kind of symptoms that could be used as a preventive measure against the development of sleep apnea. For all the previous reasons, the aim of this study is to assess whether there are any differences in daytime sleepiness, reaction time, short-term memory, depression, trait anxiety, state anxiety and neuroticism between a group of patients with obstructive sleep apnea and a group of snoring individuals who had not been diagnosed as suffering from OSAS. Material and method: The sample was made up of 11 snorers (two women and nine men), in an age range between 29 and 58 (X= 43.82 and SD= 8.67), and 14 patients with OSAS (two women and 12 men), in the age range between 30 and 65 (X= 49.64 and SD= 10.67), who were selected from a clinical population. The AHI used for establishing an OSAS diagnostic was of 10 apneas/hypopneas per sleeping hour. The patients were diagnosed to be snorers if they showed an apnea/hypopnea index <10. The following instruments were used in the evaluation of snoring subjects and obstructive sleep apnea patients: 1. Cardio-respiratory polygraph of every hour of sleep for each one of the patients. The procedure consists in night-time monitoring of the following parameters: a) electrocardiogram; b) respiratory movements (expansion and relaxation of the thorax and abdomen), which evaluate the respiratory force; c) oronasal flow and d) oxygen saturation. The snoring was measured through a tracheal microphone. 2. To measure the subjective daytime sleepiness, the Epworth Sleepiness Scale was used. 3. A BASIC software program was used to measure the simple perceptual reaction times in milliseconds. 4. The digits test of WAIS was used in straight and inverse order to evaluate the capacity of short term memory. 5. To evaluate the depressive symptoms, the Beck's Depression Inventory was employed. 6. The State/Trait Anxiety Inventory was used as a measurement of the state and trait anxiety levels. 7. As an index of neuroticism levels, the Eysenck Personality Inventory was used. Subjects under clinical risk of an OSAS diagnosis were referred to a sleep unit by primary care physicians. Respiratory pathologies other than OSAS were ruled out before the subjects' inclusion. Among these were, in particular, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease. All the patients underwent a medical examination and a medical interview in which a detailed clinical history of each patient was compiled. Once the medical examination was over, each patient was given an appointment to sleep one night in hospital. Subsequently, cardio-respiratory poligraphy, registering height hours of sleep, was administered to each patient with the objective to establish a diagnosis. The morning after, a manual analysis was made of the following parameters which indicate the presence or absence of the disturbance and its severity: total number of nocturnal obstructive apneas, total number of hypopneas, value of saturation during the night, mean and minimum levels of SaO2% and apnea/hypopnea index. Afterwards, the sleep apnea diagnosis was established for those patients who showed an apnea/hypopnea index higher than 10. Snoring subjects with a lesser apnea/hypopnea index than 10 did not fit into the pathology of sleep apnea. Obstructive apneas were defined as the arrest of air flux during sleep along with the occurrence of respiratory movements lasting more than 10 seconds. Hypopnea was defined as an episode during which the partial obstruction of the upper airways produced a significant reduction of the air flux. The following morning, the psychological variables were evaluated (daytime sleepiness, short-term memory, reaction time, depression, neuroticism, state and trait anxiety). This process was carried out in the same place and under the same conditions for every subject. The tests were completed between 8:30 and 11:30 in the morning. Additionally, an exclusion criterion was established as the suffering from any psychiatric illness past or present in any way that could influence the psychological functioning of the patient. As a method of analysis of the results, a non-parametric analysis technique was used: the U Mann-Whitney test. All statistical analyses were made with the statistics package SPSS, 8.0, Spanish version. Results: Results from this study show that there are statistically significant differences between daytime sleepiness (p<0.05) and depressive symptoms (p<0.01) between both groups of subjects, whereas no statistically significant differences were found in terms of short term memory, reaction time, state anxiety levels, trait anxiety and neuroticism. Conclusions: The analysis of the results obtained reveals that the levels of daytime sleepiness are much higher in patients with OSAS than those in the snoring group. Some studies note that the fragmentation of sleep is responsible for excessive sleepiness during the day. Nevertheless, in this study we observed greater levels of obesity in patients with OSAS than in snoring patients, which could also explain the greater levels of sleepiness. In relation to the depression variable, the average scores show that depression levels are higher in apnea patients than in the snoring group. One of the possible explanations of this result is that the majority of apnea patients, due to the severity of the pathology, consequently present higher deficits in their daily social functioning, etc. Probably, the conditions previously described tend to influence an increase of depression levels.
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