Fragile X Syndrome

The relationship between early maternal responsivity and later child communication outcomes in young children with fragile X syndrome was investigated. Data were obtained from 55 mother–child dyads over a 36-month period. Performance data were obtained at each measurement point from video observations of four different contexts. These were coded for (a) child communication behaviors, (b) parent responsivity, and (c) behavior management behaviors. Results indicate that early maternal responsivity predicts the level of four important child language outcomes at 36 months of age after controlling for child developmental level and autism symptomology.

Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). The presence of significant socioemotional problems has been well documented in FXS although the brain basis of those deficits remains unspecified. Here, we investigated amygdala dysfunction and its relation to socioemotional deficits and FMR1 gene expression in children and adolescents on the FX spectrum (ie, individuals whose trinucleotide CGG repeat expansion from 55 to over 200 places them somewhere ...

Altered dendritic spines are characteristic of traumatized or diseased brain. Two general categories of spine pathology can be distinguished: pathologies of distribution and pathologies of ultrastructure. Pathologies of spine distribution affect many spines along the dendrites of a neuron and include altered spine numbers, distorted spine shapes, and abnormal loci of spine origin on the neuron. Pathologies of spine ultrastructure involve distortion of subcellular organelles within dendritic spines. Spine distributions are altered on mature neurons following traumatic lesions, and in progressive neurodegeneration involving substantial neuronal loss such as in Alzheimer's disease and in Creutzfeldt-Jakob disease. Similarly, spine distributions are altered in the developing brain following malnutrition, alcohol or toxin exposure, infection, and in a large number of genetic disorders that result in mental retardation, such as Down's and fragile-X syndromes. An important question is whether altered dendritic spines are the intrinsic cause of the accompanying neurological disturbances. The data suggest that many categories of spine pathology may result not from intrinsic pathologies of the spiny neurons, but from a compensatory response of these neurons to the loss of excitatory input to dendritic spines. More detailed studies are needed to determine the cause of spine pathology in most disorders and relationship between spine pathology and cognitive deficits.

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability (ID) and a known monogenic cause of autism spectrum disorder (ASD). It is a trinucleotide repeat disorder, in which more than 200 CGG repeats in the 5' untranslated region (UTR) of the fragile X mental retardation 1 (FMR1) gene causes methylation of the promoter with consequent silencing of the gene, ultimately leading to the loss of the encoded fragile X mental retardation 1 protein, FMRP. FMRP is an RNA binding protein that plays a primary role as a repressor of translation of various mRNAs, many of which are involved in the maintenance and development of neuronal synaptic function and plasticity. In addition to intellectual disability, patients with FXS face several behavioral challenges, including anxiety, hyperactivity, seizures, repetitive behavior, and problems with executive and language performance. Currently, there is no cure or approved medication for the treatment of the underlying causes of FXS, but in the past few years, our knowledge about the proteins and pathways that are dysregulated by the loss of FMRP has increased, leading to clinical trials and to the path of developing molecular biomarkers for identifying potential targets for therapies. In this paper, we review candidate molecular biomarkers that have been identified in preclinical studies in the FXS mouse animal model and are now under validation for human applications or have already made their way to clinical trials.

Le Syndrome du X-Fragile (SFX) renvoie à une famille de problèmes médicaux et développementaux liés à une réplication de la portion Xq27.3 du chromosome X. Le syndrome est caractérisé par un profil langagier et communicationnel typique influencé, notamment, par des particularités cognitives et comportementales (dont de fréquent traits autistiques). La description précise de la trajectoire développementale du langage et de la communication constitue un enjeu clinique majeur pour la prise en charge adaptée de ces personnes.

Recent insight into the underlying molecular and cellular mechanisms of fragile X syndrome (FXS) has led to the proposal and development of new pharmaceutical treatment strategies, and the initiation of clinical trials aimed at correcting core symptoms of the developmental disorder. Consequently, there is an urgent and critical need for outcome measures that are valid for quantifying specific symptoms of FXS and that are consistent across time. We used eye tracking to evaluate test–retest reliability of gaze and pupillometry measures in individuals with FXS and we demonstrate that these measures are viable options for assessing treatment-specific outcomes related to a core behavioral feature of the disorder.

Gaze avoidance is a hallmark behavioral feature of fragile X syndrome (FXS), but little is known about whether abnormalities in the visual processing of faces, including disrupted autonomic reactivity, may underlie this behavior. Eye tracking was used to record fixations and pupil diameter while adolescents and young adults with FXS and sex- and age-matched typically developing controls passively viewed photographs of faces containing either a calm, happy, or fearful expression, preceded by a scrambled face matched on luminance. Results provide quantitative evidence for significant differences in gaze patterns and increased pupillary reactivity when individuals with FXS passively view static faces. Such abnormalities have significant implications in terms of understanding causes of gaze avoidance observed in individuals with FXS.

Con el avance de la edad se ha observado una declinación progresiva de los andrógenos sanguíneos, los cuales desempeñan distintos papeles en el comportamiento sexual, metabolismo óseo, masa muscular y distribución de las grasas, estado de ánimo, bienestar y actividad intelectual. En el proceso de envejecimiento también ocurren cambios profundos en otras hormonas como la hormona del crecimiento, dehidroepiandrosterona (DHEA), melatonina, y en menor medida tiroxina y leptinas. Sin embargo, los términos de declinación androgénica en el hombre maduro (ADAM por las siglas en inglés de Androgen Deficiency of Aging Male), la declinación parcial androgénica (PADAM), o el más ampliamente conocido andropausia, se usan hoy en día como sinónimos de un mismo síndrome caracterizado por alteraciones de libido y de la erección, cambios en el humor y depresión, disminución de la fuerza muscular y del vello corporal, cambios en la piel, osteoporosis e incremento de la grasa visceral. Este trabajo muestra diferentes cuestionarios para el diagnóstico y seguimiento de andropausia. Cuando hay sospecha de hipogonadismo se recomienda la determinación de la testosterona biodisponible o de la testosterona libre con toma de la muestra entre las 8 y 11 AM. Distintas preparaciones se usan para la terapia hormonal sustitutiva, el undecanoato de testosterona no produce lesión hepática, con buenos niveles plasmáticos de testosterona. Se recomienda el manejo multidisciplinario.


Palabras clave: Andropausia, PADAM, terapia hormonal sustitutiva con testosterona, envejecimiento.

Autism is a neurodevelopmental disorder of unknown etiology. There is convincing data for the involvement of genetic factors in the development of autism, and the absence of any consistent evidence for an environmental, neuroanatomical, or biochemical cause has led to an increasing number of genetic studies to determine the basis of this complex disorder. The results of recent genetic linkage and candidate gene studies are reviewed in relation to the challenge of clinical and genetic heterogeneity, and prospects for the future of genetic research in autism are considered.

New research suggests that common pathways are altered in many neurodevelopmental disorders including autism spectrum disorder; however, little is known about early molecular events that contribute to the pathology of these diseases. The study of monogenic, neurodevelopmental disorders with a high incidence of autistic behaviours, such as fragile X syndrome, has the potential to identify genes and pathways that are dysregulated in autism spectrum disorder as well as fragile X syndrome. In vitro generation of human disease-relevant cell types provides the ability to investigate aspects of disease that are impossible to study in patients or animal models. Differentiation of human pluripotent stem cells recapitulates development of the neocortex, an area affected in both fragile X syndrome and autism spectrum disorder. We have generated induced human pluripotent stem cells from several individuals clinically diagnosed with fragile X syndrome and autism spectrum disorder. When different...