Top PDF Mitochondrial disease in autism spectrum disorder patients: a cohort analysis.

Mitochondrial disease in autism spectrum disorder patients: a cohort analysis.

Mitochondrial disease in autism spectrum disorder patients: a cohort analysis.

Recently, there has been increased concern regarding a possible causative role of vaccinations in autistic children with an underlying mitochondrial cytopathy [35,36]. For one of our 25 patients, the child’s autism/neurodevelopmental deterioration appeared to follow vaccination [12,36]. Although there may have been a temporal relationship of the events in this case, such timing does not prove causation. That said, there might be no difference between the inflammatory or catabolic stress of vaccinations and that of common childhood diseases, which are known precipitants of mitochondrial regression [37]. Large, population-based studies will be needed to identify a possible relationship of vaccination with autistic regression in persons with mitochondrial cytopathies. In addition to atypical developmental patterns, non-neurological disorders were nearly universal in our patients. Although medical co- morbidities are not uncommon in individuals with ASD, they are not reported to be present with the high frequency noted here [38]. As in persons with idiopathic ASD, gastrointestinal dysfunction represent- ed the most common non-neurological abnormality in our cohort. However, several of our patients had pancreatic dysfunction or liver disease–gastrointestinal disorders that are rare in persons with ASD [39,40]. The other organ system dysfunctions in our patients (cardiac, hematological, growth retardation, fatigability) are known manifestations of mitochondrial disease [41–43] but are not typical co-morbidities of primary autism [38].
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Genetic Evidence for Elevated Pathogenicity of Mitochondrial DNA Heteroplasmy in Autism Spectrum Disorder.

Genetic Evidence for Elevated Pathogenicity of Mitochondrial DNA Heteroplasmy in Autism Spectrum Disorder.

Although ASD is traditionally described as a developmental disorder of the central nervous system, emerging evidence suggests that systemic physiological abnormalities, including dysre- gulated inflammation and immune system [6,7], elevated oxidative stress [8], and mitochon- drial dysfunction [9–12], are present in peripheral tissues as well as in brains of autistic patients [13]. Epidemiological studies also identified a staggeringly high comorbidity between ASD and mitochondrial disorder (MD) [14]. MD is a heterogeneous group of diseases due to maternally inherited or sporadic defects in genes encoding the mitochondrial oxidative phos- phorylation (OXPHOS) system [15], the core functional component of mitochondria responsi- ble for generating energy. MD usually results from genetic mutations on nuclear DNA or mitochondrial DNA (mtDNA) genes [15]. It has an extremely low birth prevalence of 6.2 in 100,000 children [16] and only about 1 in 4,300 adults is affected or at risk of developing MD [17]. However, the incidence of MD among autistic patients is estimated up to 5% by some studies [14], over 200-fold the incidence of MD in general populations. In addition, expression of OXPHOS genes has been shown to decrease in brains of autistic patients [18], suggesting a biological overlap in the pathogenesis of MD and ASD. Moreover, decreased activity of the five OXPHOS complexes has been observed in leukocytes, buccal cells, muscle biopsies and brains of autistic patients [11,14,19], suggesting the increased MD incidence among autistic patients is due not to a specific protein defect but to defects across components of the OXPHOS system.
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Subtelomeric region of chromosome 2 in patients with autism spectrum disorders

Subtelomeric region of chromosome 2 in patients with autism spectrum disorders

These indings suggest that in 2q there are genes involved in the etiology of ASDs and that some patients may have submicroscopic subtelomeric alterations that explain the cause of the disorder (Riegel and Schinzel, 2002; Sherr et al., 2005). The alterations de- scribed at 2q37 are very slight and may be underestimated in the ASD population, as they cannot be detected by cytogenetic analysis using routing GTG banding, to which the pa- tients are generally submitted in their clinical genetic evaluation. Thus, studies that utilize the FISH technique may be more enlightening.
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Mitochondrial Energy-Deficient Endophenotype in Autism

Mitochondrial Energy-Deficient Endophenotype in Autism

15q inverted duplication with autism and mitochondrial dysfunction: Chromosomal rearrangements have proven to be critical landmarks in the development of our understanding of genetic disease. Particularly propitious for the discovery of disease mechanism is the paradigm that arises when a characteristic chromosomal rearrangement is recognized in a rare subset of individuals with the disease, as the rearrangement often disrupts the function of a critical gene in the pathway leading to the disease. An important step towards highlighting an energy- deficient endophenotype of autism arose in this context. Our University California, Irvine (UCI) autism center reported that two unrelated children rigorously defined to have autism --- by Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), Autism Diagnostic Observation Schedule-Generic (ADOS-G) and Autism Diagnostic Interview- Revised (ADI-R)--- in whom we had identified a panel of biochemical signs of mild mitochondrial dysfunction including a secondary carnitine deficiency, also both had an inverted duplication of chromosome 15q11-q13 [39] . Both had uneventful perinatal courses, moderate motor delay, severe hypotonia, periods of moderate to severe lethargy (particularly during an intercurrent illness), elevated urinary lactic acid, elevated serum alanine, lactate and pyruvate and normal electroencephalograms (EEG) and magnetic resonance imaging (MRI) scans. The first child’s mitochondrial enzyme assay on muscle showed partial deficiency of respiratory complex III with pronounced mitochondrial hyper-proliferation. The second child’s muscle biopsy showed only mitochondrial hyper-proliferation. Assay of the mitochondrial enzymes in skin fibroblasts from both children showed hyper-proliferation and a relative complex III deficiency. Mitochondrial hyper- proliferation reflects a subtle defect in mitochondrial energy production to which the organelles themselves respond by added rounds of division, increasing the number of mitochondria per cell. Karyotype analysis revealed that each patient carried an extra marker chromosome and detailed fluorescent in situ hybridization (FISH) studies revealed that the marker chromosome in both of these patients contains a duplicated segment from the 15q11 – 13 chromosomal region that is at least 22,810Kb in length. Presumably
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Investigation on the Effectiveness of Holistic Multi-dimensional Treatment Model (HMTM) in Improvement of CARS Test Indicators in Children suffering from Autism Spectrum Disorder

Investigation on the Effectiveness of Holistic Multi-dimensional Treatment Model (HMTM) in Improvement of CARS Test Indicators in Children suffering from Autism Spectrum Disorder

Every feature of CARS is associated with several features of HMTM. This means given the complexity and magnitude of autism spectrum disorders, the patients should be evaluated more precisely with more details for diagnosis and assessment of treatment process. For example, the characteristic of communication with the people examined in CARS test contains subsets that are important and raise various aspects of this type of communication. It can be concluded that HMTM test, which examines each of the patient's communication and behaviors separately in details, is more suitable for diagnosis and assessment of disease treatment process. Some of CARS features having many relationships that with some features of HMTM according to the correlation coefficients obtained are specified in (Table 2). In fact, these tables show the connections that have been proven quantitatively.
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Autism spectrum disorder in a girl with a de novo x;19 balanced translocation

Autism spectrum disorder in a girl with a de novo x;19 balanced translocation

Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with pheno- typically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with a de novo X;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed a de novo balanced translocation, with the karyotype 46,X,t(X;19)(p21.2;q13.4). Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY). Although abnormal phenotypes associated with de novo balanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process.
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RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease.

RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease.

Hirschsprung disease (HSCR) is a congenital developmental malformation characterised by the absence of enteric ganglion cells of myenteric and submucosal plexuses in the intestine. The incidence of the disease is 1 per 5000 live births. Short-segment aganglionosis (80%) and long-segment aganglionosis (20%) are classified according to the length of the aganglionic segment. The short-segment form of HSCR (S-HSCR), comprising recto sigmoid HSCR and ultra-short segment HSCR, affects the distal portion, part of the anal canal and, in contrast to long-segment HSCR, occurs four times more often in males than females. The long-segment form of HSCR (L-HSCR) can present as total colonic aganglionosis (TCA) extending from the rectum up to the terminal ileum and, in rare cases, as nearly total bowel (NTBA) or total intestinal aganglionosis (TIA) comprising nearly total or the whole intestine. It occurs as an isolated disorder in 70% of cases, about 12% of cases have a chromosomal abnormality and 18% of cases have additional congenital anomalies [1].
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Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with autism spectrum disorder.

Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with autism spectrum disorder.

ASD is a genetically heterogeneous disease, with a complex genetic architecture [4]. In particular, rare SNVs with a multigenic contribution are expected to play a specific role in the molecular pathogenesis of ASD. We have shown that our workflow works rapidly and inexpensively to address this issue by demonstrating our successful identification of novel candidate SNVs in ASD. Notably, A19V in PNKP was identified significantly more in patients with ASD than controls. PNKP (polynucleotide kinase 39-phosphatase ) is a bi-functional enzyme that possesses both DNA 39-phosphatase and DNA 59-kinase activities, and associates with the single strand break repair machinery. Single strand break could be hazardous to the cell if left unrepaired, especially in central nervous system since frequently single strand breaks could happen [28]. PNKP is mutated in microcephaly, early-onset, intractable seizures and developmental delay (MCSZ), in autosomal recessive manner. Patients with MCSZ sometimes show variable behavioral problems, mainly hyperactivity [29]. Considering enzymatic activity of PNKP and its stability as reported [30], clinical symptoms of individuals with the hetero- zygous variant may not be as severe as MCSZ, however it could not be denied that possible decrease in enzyme activity or protein level of PNKP comparing to wild type might affect the normal development of central nervous system. It was implied that PNKP might be a candidate for ASD-related gene by copy number analysis previously [31]. We showed for the first time a candidate variant associated with ASD. Further study with larger samples is necessary to confirm its pathogenicity. It is also noted that there were some genes such as CHD7, CNTNAP2, DMD, and RAI1, in which two patients had private rare variants. It is speculated that the private variants of those might accumulate in ASD popula- tions.
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QUANTITATIVE EEG COMPARATIVE ANALYSIS BETWEEN AUTISM SPECTRUM DISORDER (ASD) AND ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD)

QUANTITATIVE EEG COMPARATIVE ANALYSIS BETWEEN AUTISM SPECTRUM DISORDER (ASD) AND ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD)

A total of 156 children participated in the present study. The normal control (NC) subjects were recruited from local primary schools. Parents were invited to complete and return the consent form to the research team if they agreed to have their children participate in the project. Children who had a history of neurological problems or abnormal developmental milestones were excluded from the study, resulting in a control group of 75 children. ASD patients were 79, including 52 low functioning and 27 high func- tioning autistic children. ADHD patients were 34. Mean age was 4.82 years, age range was 3-7 years, gender ratio (male/ female) was 59/16 for the control group, 50/12 for low func- tioning ASD, 21/6 for high functioning ASD, and 27/7 for ADHD subjects. Children with ASD and these with ADHD were either recruited from the Association of the Resource centres in Bulgaria, or from the subject database of the Clinic for Children psychiatry at the Medical university of Varna. Children with ASD and ADHD had previously been diagnosed by specialists at the University clinics in the country.
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Autism spectrum disorder and celiac disease : no evidence for a link

Autism spectrum disorder and celiac disease : no evidence for a link

INOVA Diagnostic, Inc. CA, USA). According to the manufac- turer’s instructions, the upper limit of the normal range was established as 20 arbitrary units. All patients who displayed values above the upper limit in the antigliadin or anti-trans- glutaminase tests underwent further testing for the pres- ence of anti-endomysium-specific antibodies (IgA-EMA). The IgA-EMA assay was performed using indirect immuno- fluorescence with cryosections of distal monkey esophagus (Binding Site, Birmingham, UK). Two independent observers examined all the slides, and the presence of brilliant green re- ticulin-like staining of smooth muscle under the fluorescence microscope was considered a positive result. In the present study, the IgA-tTG test (more sensitive but less specific) was used as a preliminary screening test, while the IgA-EMA one was considered a confirmatory test.
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J. Pediatr. (Rio J.)  vol.92 número6

J. Pediatr. (Rio J.) vol.92 número6

In the current survey, hypertension, hypotension, and threatened abortion were more frequent in the first group (respectively 10% vs. 5.9%, 2% vs. 0%, and 10% vs. 5.9% in the second group). These conditions are generally related to fetal loss and adverse infant outcomes, such as prematurity, intrauterine growth retardation, still birth, and neonatal death indicating fetal distress. Likewise, fetal hypoxia is one of the manifestations of fetal distress and has been reported to induce conditions such as placental abruption, threatened premature delivery, emergency cesarean section, forceps delivery, spontaneous abortion, and varying degrees of cere- bral damage. 4,5 Accordingly, ASD was linked to fetal distress:
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IMC e alterações do comportamento alimentar em pacientes com Transtorno do Espectro Autista / BMI and variations of eating behavior in patients with Autism Spectrum Disorder

IMC e alterações do comportamento alimentar em pacientes com Transtorno do Espectro Autista / BMI and variations of eating behavior in patients with Autism Spectrum Disorder

Introduction: Autism is a behavioral syndrome that results in difficulties in social interaction, communication and cognition, with stereotyped behavior as one of its main characteristics. Several current studies show the correlation between modification of eating behavior and the Body Mass Index (BMI) in patients with Autistic Spectrum Disorder (ASD). Objective: analyze the frequency of overweight, obesity and low weight for age in patients with Autistic Disorder assisted by the Association of Parents and Friends of Exceptional People (APAE) in Goiânia and Anápolis and to relate variations in BMI with the prevalence of variation in eating behavior. Methods: This is a quantitative cross-sectional study, carried out through the application of the Scale of Assessment of Eating Behavior questionnaire for parents of patients diagnosed with Autistic Disorder being monitored at APAE in Goiânia and Anápolis. Results: Eating and eating disorders were found in 100% of the sample, in varying degrees. The sample consisted of 32 patients, which 84.4% are male and 15.6% female. The average height and body mass index (BMI) were 1.43 meters and 19.4 kg / m², respectively. The median body mass was 35.0 kg. Regarding BMI, 25% were underweight for age, 18.8% were overweight, 18.8% were obese and 37.4% were eutrophic. Conclusion: Eating disorders are very commom among the autistic population, however, it was not possible to relate the presence of variation in eating behavior to variations of BMI.
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IOM Committee rejects causal relationship between MMR vaccine and autism spectrum disorder

IOM Committee rejects causal relationship between MMR vaccine and autism spectrum disorder

An analysis of the impact of decentralization and health sector reform on immunization programs was presented, illustrated by the results of 16 evaluations of national immunization programs performed in the last four years by countries and an international team assembled by PAHO. An invitation was extended to World Bank Task Managers to take part in these country evaluations in the future. In the area of vaccine introduction, discussion focused on PAHO’s efforts in generating information for the sustainable intro- duction of new vaccines, and the Organization’s efforts in supporting countries to use quality vaccines in immunization programs. An overview of the key elements of the PAHO Revolving Fund for Vaccine Procurement and its role over the past 20 years in providing a continuous and reliable source of funds for the purchase of vaccines at affordable prices was also discussed.
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Developmental trajectories of resting EEG power: an endophenotype of autism spectrum disorder.

Developmental trajectories of resting EEG power: an endophenotype of autism spectrum disorder.

Current research suggests that autism spectrum disorder (ASD) is characterized by asynchronous neural oscillations. However, it is unclear whether changes in neural oscillations represent an index of the disorder or are shared more broadly among both affected and unaffected family members. Additionally, it remains unclear how early these differences emerge in development and whether they remain constant or change over time. In this study we examined developmental trajectories in spectral power in infants at high- or low-risk for ASD. Spectral power was extracted from resting EEG recorded over frontal regions of the scalp when infants were 6, 9, 12, 18 and 24 months of age. We used multilevel modeling to assess change over time between risk groups in the delta, theta, low alpha, high alpha, beta, and gamma frequency bands. The results indicated that across all bands, spectral power was lower in high-risk infants as compared to low-risk infants at 6- months of age. Furthermore high-risk infants showed different trajectories of change in spectral power in the subsequent developmental window indicating that not only are the patterns of change different, but that group differences are dynamic within the first two years of life. These findings remained the same after removing data from a subset of participants who displayed ASD related behaviors at 24 or 36 months. These differences in the nature of the trajectories of EEG power represent important endophenotypes of ASD.
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Arq. NeuroPsiquiatr.  vol.73 número5

Arq. NeuroPsiquiatr. vol.73 número5

he diferences observed in visual ixation at social stim- uli of patients with RS and TD children are perhaps super- estimated, since they were not age-matched in our study. We sure understand that TD young children are not the more ad- equate control to understand social preferences in RS; on the other hand, comparisons between RS and TD children are not an easy or even feasible task, since age-matched groups, especially considering older patients, would probably result in huge developmental diferences, and to match them by intellectual tests is still impossible. Our clinical experience along 50 years show us that is very diicult to follow rigorous scientiic criteria when studying RS, especially regarding the composition of a realistic control group.
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Decreased coherent motion discrimination in autism spectrum disorder: the role of attentional zoom-out deficit.

Decreased coherent motion discrimination in autism spectrum disorder: the role of attentional zoom-out deficit.

Figure 1A). The number of dots was approximately 17 per deg 2 at each frame. Frame duration was 16.7 ms. The dots density remained constant through the trial. The dots were constructed in 3 sets plotted in sequence. For each set, the probability that a dot moved in a specific direction as opposed to randomly is given by the coherence value. Consequently, this routine generated dots with a limited lifetime of 3 frames (corresponding to ,50 ms) after that the dot was randomly relocated in another position inside the display. Dots’ speed was 12 deg/sec in both conditions. The CDM display duration was 300 ms, which is around the lower limit to allow global motion integration [40]. Stimuli were presented briefly enough to prevent saccades to the dots display or pursuit attempts. Participants were asked to discriminate the direction of dot movement (upward, downward, leftward or rightward), and only response accuracy was collected (we specified to the participants that response speed was not relevant). All the parameters of our CDM task are within a typical range found in previous literature [41]. There were four levels of coherence, randomly intermixed, at which dots could move (10, 20, 30 and 80%). These values were chosen on the basis of pilot observations. The experimental session consisted of 160 trials, 80 in the central condition and 80 in the peripheral condition (20 trials for each coherence level). The two blocked conditions were counter- balanced across participants.
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CoDAS  vol.27 número2

CoDAS vol.27 número2

Looking at each group individually, group SLI performed better in imitation tasks of sequential schemes compared to generic motion gestures. Previous studies have pointed out that the context of everyday actions in this population can be a facilitator and booster of the development of the ability to imitate because it allows integration of relevant information to the child’s context (8-11) .

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Mapa do Transtorno do Espectro Autista em Maceió-Alagoas / Map of Autism Spectrum Disorder in Maceió-Alagoas

Mapa do Transtorno do Espectro Autista em Maceió-Alagoas / Map of Autism Spectrum Disorder in Maceió-Alagoas

Objective: To map the Autism Spectrum Disorder (ASD) in the institutions of the city of Maceió- Alagoas in order to portray the distribution and characteristics of the population of diagnosed people. Methodology: This is a population-based epidemiological study, with a descriptive design, with the population of people diagnosed with ASD in the city of Maceió- Alagoas. The data were collected, transported to the Microsoft Office Excel program and tabulated. Subsequently, the distribution and characteristics of people with ASD in the municipality of Maceió-Alagoas and continued or interrupted schooling were analyzed. Results: The collection was carried out in the period from 2018 to 2020 in 763 records, where the predominant age group was 10 to 14 years old, male; International Classification of Diseases (ICD) F84.0 was the prevalent diagnosis, although the percentage of medical records that did not have an ICD record was considerable. As for education, the predominant rate was that of incomplete primary education, however, the data corresponding to interrupted schooling was high, in addition to the existence of a large percentage of institutions that do not record schooling in their medical records. Conclusion: It is concluded that the people diagnosed with ASD in care in the investigated institutions were predominantly male, aged between 10 and 14 years old, presented the ICD F84.0, in addition to, in some cases, having other associated diagnoses/ comorbidities to ASD.
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Children with Autism Spectrum Disorders have "the working raw material" for time perception.

Children with Autism Spectrum Disorders have "the working raw material" for time perception.

Finally, we can also relate our findings to one current mainstream hypothesis concerning autism, which suggests that it involves atypical information processes, where information seems to be primarily processed analytically – or locally – rather than in the typical holistic – or global – way [74]. This processing bias implies that people with autism do not naturally tend to integrate elements into a higher level of organization, as suggested by the Weak Central Coherence hypothesis [75], [76]. Although speculative at this point, it is thus conceivable that, whereas ASD individuals have the raw material to perceive time, their difficulties on some temporal judgements suggested in clinical reports reflect fundamentally atypical information processing involving higher cognitive processes. Indeed, time constitutes complex information that needs to be integrated without any particular sense organ being dedicated to time processing, and in variable contexts. Although not related to timing tasks per se, some findings related to the management of temporal elements are consistent with this interpretation. For example, findings showed that people with autism perform as the same way as a control group to plan a movement when instructions as to task requirements were given immediately prior to the movement, whereas they failed to perform as well when the instructions were only accessible in the movement environment [77]. In the same way, a recent study showed that on a perceptual simultaneity task, people with ASD showed impaired temporal integration, but over- performed in temporal resolution [71]. It is thus important to further investigate the specificity of time disturbances in ADS individuals as a function of type of task employed.
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CoDAS  vol.28 número6

CoDAS vol.28 número6

- ICD 10, Speciic Developmental Disorders of Speech and Language, herein simpliied as Speciic Language Impairment (SLI), occur when the normal modules of language acquisition are compromised from the earliest stages of development. They are essentially determined by poor performance in formal, standardized tests of receptive and expressive language and are based on the absence of physical, sensory, motor and/or intellectual changes. They may be accompanied by disturbance of interpersonal relationships and emotional and behavioral disorders. There is broad heterogeneity of proiles and no etiological generalization for all cases, which can vary in level of severity. Still, it is possible to identify problems in the reception and emission of oral language in most of them (6) .
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