Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): A Gender Perspective.

Although larger trinucleotide expansions give rise to a neurodevelopmental disorder called fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a "premutation" (55-200 CGG repeats) in the FMR1 gene. FXTAS is one of the more common single-gene forms of late-onset ataxia and tremor that may have a more complex development in women, with atypical presentations. After a brief presentation of the atypical case of an Italian woman with FXTAS, who had several paroxysmal episodes suggestive of acute cerebellar and/or brainstem dysfunction, this article will revise the phenotype of FXTAS in women. Especially in females, FXTAS has a broad spectrum of symptoms, ranging from relatively severe diseases in mid-adulthood to mild cases beginning in later life. Female FXTAS and male FXTAS have a different symptomatic spectrum, and studies on the fragile X premutation should be conducted separately on women or men. Hopefully, a better understanding of the molecular processes involved in the polymorphic features of FXTAS will lead to more specific and effective therapies for this complex disorder.

El cerebelo y sus afecciones en los niños / The cerebellum and its conditions in children

Introducción: Cuando se piensa en estudiar el cerebelo es posible que lo primero que viene a la mente sean las siguientes preguntas: ¿cuáles son sus enfermedades?, ¿cómo se expresan clínicamente? y quizás, ¿cómo es su estructura y cuáles las funciones de este órgano? Objetivo: Examinar las principales características anatómicas y funcionales del cerebelo y relacionarlas con su expresión clínica cuando enferma, así como comentar sobre su abanico de etiologías en el niño. Métodos: Las fuentes de búsquedas fueron las bases de datos computarizadas: PubMed, Ebsco y SciELO. Se utilizaron las palabras clave: cerebelo, ataxia, erores congénicos del metabolismo y ataxias, ataxias episódicas, enfermedades progresivas del sistema nervioso y ataxias; en idioma español e inglés. Resultados: El cerebelo recepciona múltiples informaciones y las envía a diversas estructuras cerebrales por medio de las cuales modula la excitabilidad de estas estructuras y sus sistemas descendentes. Este órgano organiza, dirige, coordina múltiples funciones que se traducen en fuerza, tiempo y secuencia. El cerebelo enfermo impide que la persona ejecute sus funciones y movimientos de forma uniforme y coordinada; puede resultar afectado por un amplio abanico de posibilidades etiológicas, genéticas o adquiridas y enfermarse todo o parte de él. Consideraciones finales: El cerebelo cumple importantes funciones dentro del sistema nervioso, tiene una expresividad muy típica cuando está enfermo. El uso adecuado de las nuevas técnicas de estudios por imágenes y genéticas, entre otras, permiten al pediatra clínico estar en mejores condiciones para el diagnóstico de sus afecciones y tratamiento oportuno(AU)

Introduction: When we think about studying the cerebellum, the first thing that comes to mind may be the following questions: Which are its diseases? How they are clinically expressed? , and perhaps: What is its structure and what functions do this organ has? Objective: Examine the main anatomical and functional characteristics of the cerebellum and relate them to its clinical expression when it becomes ill, as well as comment on its range of etiologies in the child. Methods: Search sources were computerized databases like: PubMed, Ebsco, and SciELO. Keywords used were: cerebellum, ataxia, metabolism congenital errors and ataxias, episodic ataxias, progressive diseases of the nervous system and ataxias; in Spanish and English. Results: The cerebellum receives information and sends it to various brain structures through which it modulates the excitability of these structures and their downstream systems. This organ organizes, directs, and coordinates multiple functions that translate into strength, time and sequence. An ill cerebellum prevents the person from performing their functions and movements in a uniform and coordinated way; it can be affected by a wide range of etiological, genetic or acquired possibilities and make all or part of it ill. Final considerations: The cerebellum performs important functions within the nervous system; it has a very typical expressiveness when it is ill. Proper use of new imaging and genetic study techniques, among others, allows the clinical pediatricians to be better able to diagnose its conditions and timely treatment(AU)

Paroxysmal movement disorders - practical update on diagnosis and management.

Introduction: Paroxysmal dyskinesias and episodic ataxias are often caused by mutations in genes related to cell membrane and synaptic function. Despite the exponential increase in publications of genetically confirmed cases, management remains largely clinical based on non-systematic evidence. Areas covered: The authors provide a historical and clinical review of the main types of paroxysmal dyskinesias and episodic ataxias, with recommendations for diagnosis and management of patients suffering from these conditions. Expert opinion: After secondary paroxysmal dyskinesias, the most common paroxysmal movement disorders are likely to be PRRT2-associated paroxysmal kinesigenic dyskinesias, which respond well to small doses of carbamazepine, and episodic ataxia type 2, which often responds to acetazolamide. Familial paroxysmal non-kinesigenic dyskinesias are largely caused by mutations in PNKD and have poor response to therapy but improve with age. Exercise-induced dyskinesias are genetically heterogeneous, caused by disorders of glucose transport, mitochondrial function, dopaminergic pathways or neurodegenerative conditions amongst others. GNAO1 and ADCY5 mutations can also cause paroxysmal movement disorders, often in the context of ongoing motor symptoms. Although a therapeutic trial is justified for classic cases and in limited resource settings, genetic testing may help direct initial or rescue therapy. Deep brain stimulation may be an option for severe cases.

Episodic ataxias.

Primary episodic ataxias (EAs) are a group of dominantly inherited disorders characterized by transient recurrent incoordination and truncal instability, often triggered by physical exertion and emotional stress, variably associated with progressive baseline ataxia. There are now eight designated subtypes based largely on genetic loci. Mutations have been identified in multiple individuals and families with EA1, EA2, and EA6, mostly with onset before adulthood. EA1 and EA2 are prototypical neurologic channelopathies. EA1 is caused by heterozygous mutations in KCNA1, which encodes the α1 subunit of a neuronal voltage-gated potassium channel, Kv1.1. EA2, the most common and best characterized, is caused by heterozygous mutations in CACNA1A, which encodes the α1A subunit of a neuronal voltage-gated calcium channel, Cav2.1. EA6 is caused by heterozygous mutations in SLC1A3, which encodes a subunit of a glial excitatory amino acid transporter, EAAT1. The other EA subtypes were defined in single families awaiting gene identification and further confirmation. This chapter focuses on the best-characterized EA syndromes, the clinical assessment and genetic diagnosis of EA, and the management of EA, as well as newly recognized allelic disorders that have greatly expanded the clinical spectrum of EA2. Illustrative cases are discussed, with a focus on sporadic patients with congenital features without episodic ataxia who present diagnostic and therapeutic challenges.