[Autistic regression: clinical and aetiological aspects]. / Regresion autista: aspectos clinicos y etiologicos.

INTRODUCTION: Autism spectrum disorders are neurodevelopmental dysfunctions that are characterised by deficits in social integration and communication, associated with restricted interests and stereotypic behaviour. A high percentage are related to language disorders, sensory dysfunctions, attention deficit disorder, bipolarity, intellectual disability or epilepsy, among other comorbidities. It is estimated that around 30% of children with autism, with typical early development, may present regression in the first years of life, which was already reported by Kanner in one of his original cases. The term regression refers to the loss of social, communicative or motor skills. It is essential to be alert to any symptoms of autistic regression, since it is not always an unspecific usual manifestation of the clinical spectrum of autism. Although little is known about the pathogenesis of regression, it needs to be organised hierarchically, as it can be part of different conditions with a variety of causes. AIMS: The aim of this study is to analyse distinct conditions that need to be addressed in the case of a child with autistic regression, including genetic and toxic causations, autoimmune and nutritional phenomena, and epilepsies. CONCLUSION: When faced with a case of autistic regression it is essential to try to identify the possible aetiology, as this can allow specific treatment and adequate genetic counselling to be established.

TITLE: Regresion autista: aspectos clinicos y etiologicos.Introduccion. Los trastornos del espectro autista son disfunciones del neurodesarrollo que se caracterizan por deficits en la integracion social y la comunicacion, asociados a intereses restringidos y conductas estereotipadas. Un alto porcentaje se asocia a trastorno del lenguaje, disfunciones sensoriales, trastorno por deficit de atencion, bipolaridad, discapacidad intelectual o epilepsia, entre otras comorbilidades. Se estima que aproximadamente un 30% de los niños con autismo, con desarrollo tipico inicial, pueden presentar regresion en los primeros años de vida, lo cual ya fue comunicado por Kanner en uno de sus casos originales. Se denomina regresion a la perdida de habilidades sociales, comunicativas o motoras. Es esencial estar atentos ante cualquier cuadro de regresion autista, ya que no siempre es una manifestacion habitual inespecifica del espectro clinico de autismo. Si bien la patogenia de la regresion se comprende poco, debe ser jerarquizada, ya que puede ser parte de diferentes entidades con diversas etiologias. Objetivo. Analizar diferentes entidades que deben evocarse frente a un niño con regresion autista, incluyendo etiologias geneticas, toxicas, fenomenos autoinmunes, nutricionales y epilepsias. Conclusion. Frente a un cuadro de regresion autista es esencial intentar identificar la posible etiologia, dado que esto puede permitir un tratamiento especifico y un adecuado asesoramiento genetico.

[Autism: the importance of dysmorphology in the identification of associated medical conditions]. / Autismo: importancia de la dismorfologia en la identificacion de entidades medicas asociadas.

INTRODUCTION: Autism spectrum disorders (ASD) are characterized by deficits in communication and social interaction, associated with restricted interests and stereotyped behaviors. Considered as a neurodepelopment disorders, they present a recognized neurobiological basis. Genetic causes as chromosomes abnormalities, or genetic defects are the most recognized etiologies, followed by the environmental factors. DEVELOPMENT: Dysmorphia are congenital alterations of the shape of a part of a living being, produced during its development. Their recognition is essential in delineating a syndrome or a specific entity. In the case of ASD, is possible to differentiate primary or idiopathic forms, from secondary or syndromic ones. In this work we describe the dysmorphological aspects related to ASD that will allow us to define a diagnostic presumption and guide the complementary studies according to them. CONCLUSIONS: The identification of these specific medical entities, associated with ASDs is fundamental since it allows inferring the possible evolution, preventing eventual complications and granting adequate genetic counseling.

TITLE: Autismo: importancia de la dismorfologia en la identificacion de entidades medicas asociadas.Introduccion. Los trastornos del espectro autista (TEA) se caracterizan por deficits en la comunicacion e interaccion social asociados a intereses restringidos y conductas estereotipadas. Considerados trastornos del neurodesarrollo, presentan una base neurobiologica reconocida. Las causas geneticas, las anomalias cromosomicas o los defectos genicos son las etiologias mas frecuentemente reconocidas, seguidas por factores toxicos y ambientales (epigeneticos). Desarrollo. Las dismorfias son alteraciones congenitas de la forma de una parte de un ser vivo, producidas durante su desarrollo, y su reconocimiento es esencial en la delineacion de un sindrome o una entidad especifica. En el caso de los TEA permiten diferenciar las formas primarias o idiopaticas de las secundarias o sindromicas. En este trabajo describimos los aspectos dismorfologicos vinculados a los TEA que permitiran definir una presuncion diagnostica y orientar los estudios complementarios de acuerdo con ellos. Conclusiones. La identificacion de estas entidades medicas especificas, asociadas a los TEA, es fundamental, ya que permite inferir la posible evolucion, prevenir eventuales complicaciones y otorgar un asesoramiento genetico adecuado.

[Autism in females: clinical, neurobiological and genetic aspects]. / Autismo en las mujeres: aspectos clinicos, neurobiologicos y geneticos.

Autism spectrum disorders are more prevalent in males than in females, and the proportion can range from 1.4 to 1, depending on the samples that are analysed. The smaller difference has been related to those who also manifest an associated intellectual disability, and it is accepted that in those cases females are far more seriously affected. There is likely to be a subregister of females with autism spectrum disorder, especially in those who have high cognitive performance, that is possibly related with the assessment techniques that are used and even with the lack of suitable levels of arousal in girls. In general, females with autism have better early language development, better social skills and their playing can even develop in the expected way. Their interests can be similar to those of their peer group, although they usually vary in intensity and quality. It is accepted as a fact that the difference in the social skills becomes more apparent in adolescence. The extreme male brain theory, the female-specific protective factor, variants in brain plasticity (lower threshold in males with greater susceptibility) and genetic and epigenetic factors, among others, are put forward as possible hypotheses to justify this lower prevalence and the clinical variants in females. This work aims to analyse the clinical and developmental aspects, the variability of expression in females with respect to males, and some of the possible neurobiological and genetic bases that account for the higher prevalence and the differences in expression.

TITLE: Autismo en las mujeres: aspectos clinicos, neurobiologicos y geneticos.Los trastornos del espectro autista son mas prevalentes en los varones que en las mujeres, y la proporcion puede variar desde 1,4 a 1 hasta 15,7 a 1, dependiendo de las muestras analizadas. La menor diferencia se ha relacionado con quienes manifiestan ademas discapacidad intelectual asociada, y se acepta que en esos casos las mujeres se afectan mucho mas gravemente. Es probable que exista un subregistro de mujeres con trastorno del espectro autista, en especial en las que tienen alto rendimiento cognitivo, posiblemente relacionado con las tecnicas de evaluacion utilizadas e incluso con la falta de adecuados niveles de alerta en las niñas. En general, las mujeres con autismo tienen mejor desarrollo linguistico temprano, mejores habilidades sociales y su juego puede incluso desarrollarse en la forma pretendida. Sus intereses pueden ser similares a los de su grupo de pares, aunque en general varian en intensidad y calidad. Se acepta que la diferencia en las habilidades sociales se hace mas evidente en la adolescencia. La teoria del cerebro masculino extremo, el factor protector femenino, variantes en la plasticidad cerebral (menor umbral en los varones con mayor susceptibilidad) y factores geneticos y epigeneticos, entre otros, se evocan como posibles hipotesis que justifican esta menor prevalencia y las variantes clinicas en ellas. Este trabajo se propone analizar los aspectos clinicos y evolutivos, la variabilidad de expresion en las mujeres en relacion con los varones, y algunas de las posibles bases neurobiologicas y geneticas que justifican la mayor prevalencia y las diferencias de expresion.

[Atentional processes and attention deficit disorders in autism]. / Procesos atencionales y trastornos por déficit de atención en el autismo.

INTRODUCTION: Autism is recognised as being a behavioural syndrome characterised by impaired language development, restricted interests and compromised socialisation. It is accepted that persons with autism react in an inappropriate way to socially relevant information and that they are unable to benefit from important stimuli from their surroundings. A number of disorders affecting different attention processes (with the ensuing difficulty involved in selecting and hierarchising stimuli) have been put forward as probable hypotheses to account for the genesis of these problems. DEVELOPMENT: In this work we analyse some of the attentional processes reported as being due to deficits in autism (disorders affecting alertness, orientation, gaze, sustained attention and changes in focus of attention). We also examine the high rate of comorbidity of attention deficit disorders with or without hyperactivity (ADHD) with pervasive developmental disorders (PDD) and the importance of identifying them. CONCLUSIONS: Although many disorders affecting the components of attention have been reported, the findings and their importance are controversial and it is likely that their association to other cognitive disorders plays an important role in the development of autism. With regard to the association between ADHD and PDD, it is an acknowledged fact that up to 70% of the persons with PDD meet ADHD criteria; whether we are before a situation of comorbidity, it is part of the spectrum or forms a specific subtype is an interesting issue for debate. Nevertheless, what is essential is for this association to be acknowledged to allow therapy to be undertaken using the correct approach.

Procesos atencionales y trastornos por déficit de atención en el autismo / Attentional processes and attention deficit disorders in autism

Introducción. El autismo se reconoce como un síndromeconductual caracterizado por trastorno en el desarrollo del lenguaje,intereses restringidos y afectación en la socialización. Seacepta que las personas con autismo reaccionan de forma inapropiadaa información socialmente relevante y que son incapaces debeneficiarse de los estímulos importantes del entorno. Se han propuestotrastornos en diversos procesos de atención, con la consecuentedificultad para jerarquizar los estímulos y seleccionarlos,como hipótesis probables en la génesis de estas dificultades. Desarrollo.En este trabajo se analizan algunos de los procesos atencionalesdescritos como deficitarios en el autismo (trastornos en elestado de alerta, en la orientación, en la mirada, en la atenciónsostenida y en los cambios de foco de atención), y la alta comorbilidadde trastornos por déficit de atención con o sin hiperactividad (TDAH) con los trastornos generalizados del desarrollo (TGD) y laimportancia de su identificación. Conclusiones. Si bien son muchoslos trastornos en los componentes de la atención descritos, loshallazgos y su importancia son controvertidos y es probable que suasociación a otros trastornos cognitivos desempeñe un papel importanteen el desarrollo del autismo. En relación con la asociaciónentre TDAH y TGD, se ha reconocido que hasta el 70% de laspersonas con TGD cumple con los criterios de TDAH; si se trata deuna situación comórbida, forma parte del espectro o configura unsubtipo específico, es un tema interesante de debate. No obstante,lo fundamental es el reconocimiento de esta asociación para elcorrecto abordaje terapéutico

Introduction. Autism is recognised as being a behavioural syndrome characterised by impaired language development,restricted interests and compromised socialisation. It is accepted that persons with autism react in an inappropriate way tosocially relevant information and that they are unable to benefit from important stimuli from their surroundings. A number ofdisorders affecting different attention processes (with the ensuing difficulty involved in selecting and hierarchising stimuli) havebeen put forward as probable hypotheses to account for the genesis of these problems. Development. In this work we analysesome of the attentional processes reported as being due to deficits in autism (disorders affecting alertness, orientation, gaze,sustained attention and changes in focus of attention). We also examine the high rate of comorbidity of attention deficit disorderswith or without hyperactivity (ADHD) with pervasive developmental disorders (PDD) and the importance of identifying them.Conclusions. Although many disorders affecting the components of attention have been reported, the findings and theirimportance are controversial and it is likely that their association to other cognitive disorders plays an important role in thedevelopment of autism. With regard to the association between ADHD and PDD, it is an acknowledged fact that up to 70% of thepersons with PDD meet ADHD criteria; whether we are before a situation of comorbidity, it is part of the spectrum or forms aspecific subtype is an interesting issue for debate. Nevertheless, what is essential is for this association to be acknowledged toallow therapy to be undertaken using the correct approach

[Clinical and electroencephalographic aspects of late infantile neuronal ceroid lipofuscinosis]. / Lipofuscinosis neuronal ceroidea infantil tardía: aspectos clínicos y electroencefalográficos.

AIMS: In this paper we describe the clinical characteristics, and particularly the epileptic seizures and electroencephalographic findings, in 15 patients with a pathology diagnosis of late infantile neuronal ceroid lipofuscinosis (NCL). PATIENTS AND METHODS: Nine female and six male patients were studied and their clinical records covering the period February 1990 to June 2003 were analysed. Neuroimaging, neurometabolic studies, ERG, PE and repeated EEG were carried out in all cases. RESULTS: The mean age on onset of the disease was 3 years (range: 1-5 years). The initial symptom was epilepsy in all cases. Massive myoclonias and myoclonic-atonic seizures were the most frequent kinds of attacks. Focal myoclonias were observed in six patients. Other types of epileptic seizures observed included generalised tonic-clonic, absence, motor focal and complex focal. The epileptic seizures were resistant to therapy. Progressive neurological and visual impairment, pyramidal and cerebellar signs, as well as mental retardation were present in all cases. Intercritical EEG recordings showed diffuse paroxysms with spike and polyspike waves, multifocal spikes and, less often, focal spikes that were predominant in posterior regions. Photostimulation showed high amplitude (300-450) occipital spikes during the application of light stimulation between 1 and 8 Hz. ERG, VEP and SSEP results were pathological. Images showed signs of brain and cerebellar atrophy. Seven of the patients died between 8.5 and 11 years of age. CONCLUSIONS: Late infantile NCL must be considered in the case of a child aged between 1 and 5 years who presents seizures that are predominantly generalised myoclonias and myoclonic-atonic, in association with progressive neurological deterioration including pyramidal, cerebellar and visual signs and an EEG trace showing occipital paroxysms triggered by low frequency photostimulation.

Lipofuscinosis neuronal ceroidea infantil tardía: aspectos clínicos y electroencefalográficos / Clinical and electroencephalographic aspects of late infantile neuronal ceroid lipofuscinosis

Objetivo. Describimos las características clínicas, particularmente las crisis epilépticas y los hallazgos electroencefalográficos, en 15 pacientes con diagnóstico anatomopatológico de lipofuscinosis neuronal ceroidea (LNC) infantil tardía. Pacientes y métodos. Se estudiaron y se analizaron las historias clínicas de nueve pacientes del sexo femenino y seis del masculino durante el período comprendido entre febrero de 1990 y junio de 2003. En todos los casos se realizaron neuroimágenes, estudios neurometabólicos, ERG, PE y repetidos EEG . Resultados. La edad mediana de comienzo de la enfermedad fue de 3 años (intervalo: 1-5 años). La manifestación inicial fue la epilepsia en todos los casos. Las crisis más frecuentes fueron las mioclonías masivas y las crisis mioclonicoatónicas. Se observaron mioclonías focales en seis pacientes. Otros tipos de crisis epilépticas observados fueron tonicoclónicas generalizadas, ausencias, focales motoras y focales complejas. Las crisis epilépticas fueron refractarias al tratamiento. En todos los casos se presentaron deterioro neurológico y visual progresivo, signos piramidales y cerebelosos y retraso mental . Los EEG intercríticos mostraron paroxismos de punta y polipunta onda difusos, espigas multifocales y, menos frecuentemente, espigas focales predominantes en las regiones posteriores. La fotoestimulación mostró espigas occipitales de elevada amplitud (300-450) durante el estímulo lumínico entre 1 y 8 Hz. El ERG, los PE visuales y los PE somatosensoriales fueron patológicos. Las imágenes evidenciaron signos de atrofia cerebral y cerebelosa. Siete de los pacientes fallecieron entre los 8,5 y los 11 años. Conclusión. En un niño de 1-5 años que comienza con convulsiones, predominantemente mioclonías generalizadas y mioclonicoatónicas asociadas a deterioro neurológico progresivo que incluye signos piramidales, cerebelosos y visuales con un EEG con paroxismos occipitales desencadenados por la fotoestimulación a baja frecuencia, debemos pensar en una LNC infantil tardía

Aims. In this paper we describe the clinical characteristics, and particularly the epileptic seizures and electroencephalographic findings, in 15 patients with a pathology diagnosis of late infantile neuronal ceroid lipofuscinosis (NCL). Patients and methods. Nine female and six male patients were studied and their clinical records covering the period February 1990 to June 2003 were analysed. Neuroimaging, neurometabolic studies, ERG, PE and repeated EEG were carried out in all cases. Results. The mean age on onset of the disease was 3 years (range: 1-5 years). The initial symptom was epilepsy in all cases. Massive myoclonias and myoclonic-atonic seizures were the most frequent kinds of attacks. Focal myoclonias were observed in six patients. Other types of epileptic seizures observed included generalised tonic-clonic, absence, motor focal and complex focal. The epileptic seizures were resistant to therapy. Progressive neurological and visual impairment, pyramidal and cerebellar signs, as well as mental retardation were present in all cases. Intercritical EEG recordings showed diffuse paroxysms with spike and polyspike waves, multifocal spikes and, less often, focal spikes that were predominant in posterior regions. Photostimulation showed high amplitude (300-450) occipital spikes during the application of light stimulation between 1 and 8 Hz. ERG, VEP and SSEP results were pathological. Images showed signs of brain and cerebellar atrophy. Seven of the patients died between 8.5 and 11 years of age. Conclusions. Late infantile NCL must be considered in the case of a child aged between 1 and 5 years who presents seizures that are predominantly generalised myoclonias and myoclonic-atonic, in association with progressive neurological deterioration including pyramidal, cerebellar and visual signs and an EEG trace showing occipital paroxysms triggered by low frequency photostimulation

[Epilepsy beginning in the neonatal period and early infancy]. / Epilepsias de comienzo en la lactancia e infancia temprana.

INTRODUCTION: In this study we analyse several epileptic syndromes that begin in the neonatal period or early infancy, up to two years of age, and we also define their clinical, neurophysiological and progressive aspects as well as their differential diagnoses. Both neonatal and febrile convulsions are excluded. DEVELOPMENT: The different syndromes are classified according to the predominant type of seizures, which is the one that identifies them, although it is not the only type of seizure presented. In line with this reasoning, the syndromes were divided into four main groups: 1. Epileptic spasms: infantile spasms (West's syndrome), periodic spasms as described by Gobbi and bouts of epileptic seizures without hypsarrhythmia. 2. Tonic seizures: Lennox-Gastaut syndrome. 3. Myoclonias: benign myoclonic epilepsy in infancy, Dravet's severe myoclonic epilepsy, myoclonic-astatic epilepsy and a myoclonic state in non-progressive encephalopathies; and 4. Partial seizures: non-idiopathic location-related epilepsies, malign epilepsy with migratory partial seizures and benign infantile familial and non-familial seizures. CONCLUSIONS: Thus, it will be possible to establish a plan of studies, differential diagnoses and a rational therapeutic approach depending on the clinical manifestations, while at the same even enabling us to distinguish between the idiopathic, cryptogenic and symptomatic forms.

[Behavioural phenotypes. Biologically determined neuropsychological patterns]. / Fenotipos conductuales. Patrones neuropsicológicos biológicamente determinados.

INTRODUCTION AND AIMS: A behavioural phenotype (BP) is a characteristic pattern of motor, cognitive, linguistic and social abnormalities that are associated in a way that is compatible with a biological disorder, while environmental factors are also known to be important in their development. Taking these concepts into account, we have analyzed several entities with acknowledged BP, which were selected according to the frequency of presentation, the compatibility of the association between BP and the underlying disease, and the importance of recognizing the entity, so as to enable suitable therapeutic guidance and proper genetic counselling. DEVELOPMENT: They were organized by dividing them into three groups according to the biological characteristics recognized to date: a) BP associated to genetic diseases with an identified biological basis (syndromes such as Lesch Nyhan, Rett, fragile X, tuberous sclerosis complex, Noonan, Sotos, Aicardi, Angelman, Prader Willi, Williams, Down, Smith Magenis, Di George, Pallister Killian and Turner, among others; b) BP associated to a genetic disease with an unidentified biological basis (Cornelia de Lange syndrome); and, c) BP with an as yet unidentified biological basis associated to diverse causations (autism). In all the entities phenotypic, clinical, cognitive, behavioural and biological aspects were analyzed from the way they are inherited to the molecular bases.

[Neuromuscular hereditary channelopathies: non-dystrophic myotonias, paramyotonias and periodic paralysis]. / Canalopatias hereditarias neuromusculares: miotonías no distróficas, paramiotonías y parálisis periódicas.

INTRODUCTION: The ionic channels are complex glycoprotein structures, which cross the lipidic cellular membrane and allow the passage of electrically charged ions from one side of it to the other, thanks to the electrochemical gradient. A channelopathy is a disorder due to anomalous function of the ionic channels. DEVELOPMENT: In this study we analyze particularly the hereditary channelopathies with neuromuscular involvement non dystrophic myotonia, paramyotonias and periodic paralysis, and classify the clinical, physiopathological, molecular, genetic and therapeutic aspects. As far as possible we have divided the different conditions according to the channel involved, due to mutations which affect the sodium, calcium, chloride and potassium channels. We have also included neuromyotonic phenomena which are probably caused by channelopathies. CONCLUSIONS: Probably it will not be long before many of the conditions considered in this article have a better physiopathological explanation, more specific diagnostic procedures and a more rational approach to treatment.

Canalopatías hereditarias neuromusculares:miotonías no distróficas, paramiotonías y parálisis periódicas / Neuromuscular hereditary channelopathies: non-dystrophic myotonias, paramyotonias and periodic paralysis

Introducción. Los canales iónicos son estructuras glicoproteicas complejas, que atraviesan la membrana celular lipídica y que permiten el pasaje de iones con carga eléctrica, de un lado a otro de la misma, gracias a un gradiente electroquímico. Se denomina canalopatía a toda enfermedad producida por una anormalidad en el funcionamiento de los canales iónicos. Desarrollo. En este trabajo analizaremos especialmente las canalopatías hereditarias con afección neuromuscular-miotonías no distróficas, paramiotonías y parálisis periódicas, y jerarquizaremos sus aspectos clínicos, fisiopatológicos, moleculares, genéticos y terapéuticos. En la medida de lo posible, hemos dividido las distintas entidades, de acuerdo con el canal afectado, producto de mutaciones que afectan el canal del sodio, calcio, cloro y potasio. También hemos incluido a fenómenos neuromiotónicos como de probable origen canalopático. Conclusión. Es probable que a corto plazo muchas de las entidades aquí analizadas tengan una mejor explicación fisiopatológica, métodos diagnósticos más específicos y abordajes terapéuticos más racionales (AU)

[Hereditary ataxias]. / Ataxias hereditarias.

INTRODUCTION AND OBJECTIVE: The hereditary ataxias form a large, complex group of entities whose recognition is essential for correct genetic assessment, satisfactory clinical control and in some cases a suitable therapeutic approach. The clinico-semiological variety and advances in molecular biology have made the hereditary ataxias one of the most interesting subjects in neurology. In this paper our objective is to classify the clinical approach of the hereditary ataxias and define the different conditions known so as to orientate complementary investigations and thus obtain the correct diagnosis. DEVELOPMENT AND CONCLUSION: We analyze and classify them, according to their mode of presentation, as congenital (in general nonprogressive) and progressive. Both groups are then divided according to how they are inherited and we also include the specific molecular findings.

[Benign paroxysmal tonic upward gaze syndrome]. / Síndrome de desviación paroxística benigna de la mirada hacia arriba.

INTRODUCTION: The benign paroxysmal tonic upward gaze syndrome (BPTUG) is a rare condition. We present two new cases analyzing the clinical, genetic, evolution and therapeutic aspects. CLINICAL CASES: Case 1. A 2 year-old girl with no family history of similar disorders started, at the age of 6 months, to have episodes of upward deviation of gaze with hyperextension of the neck and vertical nystagmus of fixation, increased by nervousness and episodes of fever. Some episodes caused the patient to fall in spite of there being no alteration of consciousness. Case 2. From the age of five months a 1 year-old girl with no significant personal or family history had episodes of ocular deviation upwards with forward inclination of the head to correct her gaze and slow motor development from the age of five months. RESULTS: Complementary studies were normal in both patients. As in the cases described in the literature, our cases had no family history and were not sensitive to Dopa. To date 11 children have been described in the literature and few familial cases seen with dominant autosomal inheritance. CONCLUSIONS: Our patients had a non-epileptic paroxystic phenomenon known as BPTUG syndrome. This condition starts during the first year of life, has a benign course and the episodes have ceased by the age of four years. We believe it is important to consider the differential diagnosis with epileptic phenomena, evaluate the response to L-Dopa and bear in mind that this syndrome may be the clinical expression of several different conditions. Although the course is usually benign, it may later be associated with other signs of neurological problems which should be taken into account.

[An approach to the pharmacological treatment of autism]. / Abordaje terapéutico farmacológico del autismo.

In the past decade, notable advances have been made with regard to understanding the clinical, biological and epidermological aspects of the basic disorders of development (TPD), particularly autism. Nevertheless, our knowledge of the neurobiological basis is still limited. This has impeded the development of drugs which correct the defect and cure the illness. Although there is no perfect drug, in recent years clinico-pharmacological research has made it possible to use drugs which have been very helpful in correcting the symptoms associated with these disorders. These drugs have permitted a better therapeutic approach and improved family and social integration of these children (in the family and in society). We will proceed to analyze some of the drugs shown to be useful for treatment of children with TPD.