QTL mapping of melon fruit quality traits using a high-density GBS-based genetic map.

BACKGROUND: Melon shows a broad diversity in fruit morphology and quality, which is still underexploited in breeding programs. The knowledge of the genetic basis of fruit quality traits is important for identifying new alleles that may be introduced in elite material by highly efficient molecular breeding tools. RESULTS: In order to identify QTLs controlling fruit quality, a recombinant inbred line population was developed using two commercial cultivars as parental lines: "Védrantais", from the cantalupensis group, and "Piel de Sapo", from the inodorus group. Both have desirable quality traits for the market, but their fruits differ in traits such as rind and flesh color, sugar content, ripening behavior, size and shape. We used a genotyping-by-sequencing strategy to construct a dense genetic map, which included around five thousand variants distributed in 824 bins. The RIL population was phenotyped for quality and morphology traits, and we mapped 33 stable QTLs involved in sugar and carotenoid content, fruit and seed morphology and major loci controlling external color of immature fruit and mottled rind. The median confidence interval of the QTLs was 942 kb, suggesting that the high density of the genetic map helped in increasing the mapping resolution. Some of these intervals contained less than a hundred annotated genes, and an integrative strategy combining gene expression and resequencing data enabled identification of candidate genes for some of these traits. CONCLUSION: Several QTLs controlling fruit quality traits in melon were identified and delimited to narrow genomic intervals, using a RIL population and a GBS-based genetic map.

Intersection of reality and fiction in art perception: pictorial space, body sway and mental imagery.

BACKGROUND: The thesis of embodied cognition claims that perception of the environment entails a complex set of multisensory processes which forms a basis for the agent's potential and immediate actions. However, in the case of artworks, an agent becomes an observer and action turns into a reaction. This raises questions about the presence of embodied or situated cognition involved in art reception. AIMS: The study aimed to assess the bodily correlates of perceiving fictional pictorial spaces in the absence of a possibility of an actual physical immersion or manipulation of represented forms. METHOD: The subjects were presented with paintings by Vermeer and De Hooch, whilst their body sway and eye movements were recorded. Moreover, test and questionnaires on mental imagery (MRT, VVIQ and OSIQ) were administered. RESULTS: Three major results were obtained: (1) the degree of pictorial depth did not influence body sway; (2) fixations to distant elements in paintings (i.e. backgrounds) were accompanied by an increase in body sway; and (3) mental rotation test scores correlated positively with body sway. CONCLUSIONS: Our results suggest that in certain cases--despite the fictional character of art--observers' reactions resemble reactions to real stimuli. It is proposed that these reactions are mediated by mental imagery (e.g. mental rotation) that contributes to the act of representing alternative to real artistic spaces.

Are systematic drain tip or drainage fluid cultures predictive of surgical site infections?

Systematic cultures of drain tips or drainage fluids for the early detection of surgical site infections (SSIs) are controversial. To examine the association between the results of systematic drain tip or drainage fluid cultures and the occurrence of SSIs in clean or clean-contaminated surgery. Searches were performed in the PubMed, and Cat.inist databases for observational studies published before 31st March 2017. Studies reporting results of drain tip or drainage fluid systematic cultures and SSIs after clean or clean-contaminated surgeries were included, and meta-analyses were performed. Seventeen studies, including 4390 patients for drain tip cultures and 1288 for drainage fluid cultures, were selected. The pooled negative predictive values were high (99%, 95% confidence interval (CI) 98-100 for drain tip cultures and 98%, 95% CI 94-100 for drainage fluid cultures). The positive predictive values were low (11%, 95% CI 2-24 for drain tip cultures and 12%, 95% CI 3-24 for drainage fluid cultures). The sensitivities were low (41%, 95% CI 12-73 for drain tip cultures and 37%, 95% CI 16-60 for drainage fluid cultures). The specificities were high (93%, 95% CI 88-96) for drain tip cultures and moderate (77%, 95% CI 54-94) for drainage fluid cultures. Systematic cultures of drain tips or drainage fluids appear not to be relevant, because their positive predictive values were low in the prediction of SSIs.

[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.

In vitro and in vivo characterization of the bifunctional µ and δ opioid receptor ligand UFP-505.

BACKGROUND AND PURPOSE: Targeting more than one opioid receptor type simultaneously may have analgesic advantages in reducing side-effects. We have evaluated the mixed µ opioid receptor agonist/ δ opioid receptor antagonist UFP-505 in vitro and in vivo. EXPERIMENTAL APPROACH: We measured receptor density and function in single µ, δ and µ /δ receptor double expression systems. GTPγ35 S binding, cAMP formation and arrestin recruitment were measured. Antinociceptive activity was measured in vivo using tail withdrawal and paw pressure tests following acute and chronic treatment. In some experiments, we collected tissues to measure receptor densities. KEY RESULTS: UFP-505 bound to µ receptors with full agonist activity and to δ receptors as a low efficacy partial agonist At µ, but not δ receptors, UFP-505 binding recruited arrestin. Unlike morphine, UFP-505 treatment internalized µ receptors and there was some evidence for internalization of δ receptors. Similar data were obtained in a µ /δ receptor double expression system. In rats, acute UFP-505 or morphine, injected intrathecally, was antinociceptive. In tissues harvested from these experiments, µ and δ receptor density was decreased after UFP-505 but not morphine treatment, in agreement with in vitro data. Both morphine and UFP-505 induced significant tolerance. CONCLUSIONS AND IMPLICATIONS: In this study, UFP-505 behaved as a full agonist at µ receptors with variable activity at δ receptors. This bifunctional compound was antinociceptive in rats after intrathecal administration. In this model, dual targeting provided no advantages in terms of tolerance liability. LINKED ARTICLES: This article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.

[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.

[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.

Merosin-deficient congenital muscular dystrophy associated with abnormal cerebral cortical gyration: an autopsy study.

We report clinical, biopsy and autopsy findings in a merosin-deficient congenital muscular dystrophy (CMD) infant with abnormal cortical gyration. Brain showed polymicrogyria and occipital agyria with marginal neuroglial heterotopia and inferior vermis hypoplasia. There was a normal pattern of myelination consistent with early age. Laminin alpha 2 chain was also absent in myocardium, brain pial-glial membrane, brain and skin blood vessels as well as intramuscular and skin nerves. Occasional basal lamina gaps were found in muscle fibres but not in brain-blood vessels. This is the first autopsy study in a merosin-deficient CMD case with abnormal cortical gyration.

Merosin-positive congenital muscular dystrophy with mental retardation, microcephaly and central nervous system abnormalities unlinked to the Fukuyama muscular dystrophy and muscular-eye-brain loci: report of three siblings.

Classical merosin (2 laminin)-positive congenital muscular dystrophy is a heterogeneous subgroup of disorders; a few cases characterized by severe mental retardation, brain involvement and no ocular abnormalities were called Fukuyama-like congenital muscular dystrophy. We report a family of healthy non-consanguineous parents, with four affected siblings, of which one died at the age of 7 months due to an intercurrent illness, who presented congenital hypotonia, severe mental retardation, microcephaly, delayed psychomotor development, generalized muscular wasting and weakness with mild facial involvement, calf pseudohypertrophy, joint contractures and areflexia. Muscle biopsy disclosed severe muscular dystrophy. Immunostaining for laminin 2 80 kDa and clone Mer3/22B2 monoclonal antibodies, 1 and 1 chain was preserved. Magnetic resonance imaging findings were consistent with pontocerebellar hypoplasia, bilateral opercular abnormalities and focal cortical dysplasia as well as minute periventricular white matter changes. Clusters of small T2-weighted focal hyperintensities in both cerebellar hemispheres consistent with cysts were observed in two of the three siblings studied with magnetic resonance imaging. Ophthalmologic and cardiologic examination was normal. Haplotype analysis using microsatellite markers excluded the Fukuyama congenital muscular dystrophy, LAMA2 and muscle-eye-brain disease loci. Thus, a wider spectrum of phenotypes, gene defects and protein deficiencies might be involved in congenital muscular dystrophy with brain abnormalities.

Effect of increased maternal corticosterone during lactation on hippocampal corticosteroid receptors, stress response and learning in offspring in the early stages of life.

The influence of maternal corticosterone during lactation on the development of the hippocampal corticosteroid receptor system, hypothalamus-pituitary-adrenal axis activity and spatial learning/retention performance was investigated in the rat during postnatal days 11 to 30. We increased the plasma levels of corticosterone by adding the hormone (200 microg/ml) to the drinking water of the dams. When compared to controls corticosterone-nursed offspring displayed: i) higher number of hippocampal type I and type II corticosteroid receptors at 30 days of life, but no changes at 11 and 16 days; ii) higher plasma levels of corticosterone in the basal condition and after 15 min of maternal separation at 11 but not at 16 days: iii) lower adrenal weights at 11 and 16 days, but which were no longer present at the age of 30 days; iv) no difference in performance in the place learning version of the Morris water task and T aquatic maze at 16 days. The present results, together with our previous findings showing that 90-day-old corticosterone-nursed rats have lower basal and restraint stress corticosterone levels and improved learning performance, indicate that the effects of maternal treatment appears only after weaning, thereby suggesting that increased corticosteroid receptors may be responsible, at least partially, for the endocrine and learning modifications induced by pre-weaning corticosterone exposure. The role played by maternal circulating corticosterone during the period of lactation in shaping the characteristics of the hypothalamus-pituitary-adrenal axis and brain of the offspring is outlined.

Childhood neuronal ceroid-lipofuscinoses in Argentina.

We report on 30 cases of neuronal ceroid lipofuscinoses (NCL), mainly diagnosed in 1985-1993 in Argentina, whose population is predominantly of European descent. Twenty-four cases were late infantile Jansky-Bielschowsky (LINCL) and 6 were juvenile Spielmeyer-Vogt (JNCL). Sex ratio was female:male, 20:10. Age range and mean at onset and at diagnosis for the LINCL cases were 1-6 years, mean 3.1, and 2-11 years, mean 5.5, and for the JNCL cases, 5-9 years, mean 7, and 9-18 years, mean 13, respectively. Cases were referred for biopsy after neurological examination, and most included complete electrophysiological [electroencephalography (EEG) with photic stimulation, electroretinography (ERG), and visual-evoked potential (VEP)], neuroimaging, and neurometabolic investigation. NCL was the first suspected clinical diagnosis, followed by mitochondrial encephalopathy in some cases of recent onset. Except for 1 case, clinical findings were homogeneous in LINCL, characterized by refractive epilepsy, mental regression and progressive deterioration, ataxia, myoclonia, and visual loss. Abnormal VEP, ERG, and EEG, with polyphasic high-voltage spikes when photic stimulation was performed at low frequency, were observed. Visual impairment and retinitis pigmentosa were early manifestations in 4/6 JNCL, followed by mental abnormalities, motor deterioration, and myoclonic jerks, while 2/4 followed an atypical course. In both variants inheritance was autosomal-recessive. Five out of 27 families had more than 1 affected member, 3 of whom were included in our series. Diagnosis was initially performed in conjunctival biopsy in 3 cases, skin in 5, muscle in 17, and brain in 5, though most cases had a concomitant biopsy from another tissue including nerve, and there was a single brain autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced hippocampal in vitro CA1 long-term potentiation in rat offsprings with increased circulating corticosterone during neonatal life.

A moderate increase in plasma level of corticosterone was induced in dams by adding the hormone (200 micrograms/ml) to the drinking water from the day after delivery to weaning. This procedure produces a parallel increase in plasma levels of the hormone in the pups (from 0.7 +/- 0.1 to 1.2 +/- 0.2 micrograms/100 ml) at 10 days of lactation. A significant (P < 0.01) reduction in the magnitude of the long-term potentiation (LTP) of the CA1 population spike occurred in hippocampal slices obtained from 30-45 day old male corticosterone-nursed rats with respect to controls, while no significant difference occurred in the magnitude of the basal CA1 evoked extracellular somatic field potentials with respect to controls. The results demonstrate that a moderate increase in plasma corticosterone during neonatal life, obtained through maternal milk, has long-lasting effects on the hippocampal CA1 synaptic plasticity. In addition, these results together with our previous findings [Catalani, A. et al., Brain Res., 624 (1993) 209-215], demonstrating that 30 day old corticosterone-nursed offsprings perform better than controls in the place learning version of the Morris water maze, show no relationships between in vitro CA1 LTP induction and spatial learning in agreement with literature data.

Intracranial tumors and West syndrome.

Two infants, 6 and 7 months of age, are reported with both West syndrome and cerebral tumors. In both patients, initial neurologic examinations were normal and tumor diagnoses were determined through routine imaging studies. Initial response to adrenocorticotrophic hormone treatment did not differ from that observed in patients with cryptogenic West syndrome. Early treatment of West syndrome and resection of tumor, when possible, may offer successful treatment of patients with both benign brain tumors and West syndrome.

[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.

[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.

[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.

[Congenital mirror movements. Three new cases of a rare condition]. / Movimientos en espejo congénitos. Tres nuevos casos de una rara entidad.

INTRODUCTION: Mirror movements (MM) are involuntary shudders which occur at the same time as voluntary movements of the homologous contralateral muscles. They may occur alone or associated with other pathology. CLINICAL CASES: We present three new cases of congenital MM (CMM) and discuss their clinical, physiopathological and genetic aspects. Case 1. A four year old boy was brought to the clinic because he dropped things held in one hand when he tried to take things with the other. On examination it was seen that when he made a voluntary movement with one hand, the other hand made a similar movement simultaneously and involuntarily. This phenomenon had been observed since he was a few months old. Apart from this, the rest of the neurological examination was normal. Cerebral MR was also normal. Neuropsychological assessment showed borderline intellectual function. Case 2. The first patient's father, who was 26 years old, knew no details of his own family history. Since childhood he had noticed that he himself had made similar movements to those of his son. However, with time, he had managed to partially control and even inhibit these movements. His cerebral MR scan was normal. Case 3. An 11 year old boy consulted for MM, non-fluctuating congenital palpebral ptosis and nocturnal enuresis. The neurological examination and his intelligence were found to be normal. One of his sisters had palpebral ptosis and nocturnal enuresis without MM. His cerebral MR, X-ray of his spine, EMG, electroretinogram, CPK, blood lactate, glucemia, urine and urological examination were normal. CONCLUSIONS: MM may be another manifestation within the clinical spectrum of diverse encephalopathies; may be associated with different syndromes (Kallman, Klippel-Feil and Usher amongst others) or may present alone. Both familial and sporadic cases have been described. We consider our cases 1 and 2 to be of the familial CMM condition, with autosomal dominant inheritance, in which MM was the only finding. The association observed in case 3 has not previously been described. It may possibly be a condition transmitted by autosomal recessive inheritance.

[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.