[Chorea due to TITF1/NKX2-1 mutation: phenotypical description and therapeutic response in a family]. / Corea por mutacion de TITF1/NKX2-1: descripcion fenotipica y respuesta terapeutica en una familia.

INTRODUCTION: Chorea due to a mutation in the TITF1 gene, which is also known as benign hereditary chorea, is an autosomal dominant disorder that usually begins before the age of 5 years. In most cases, the chorea tends to improve as the child gets older. It may be associated to hypothyroidism and respiratory problems, such as neonatal alveolar respiratory distress syndrome or interstitial disease, since TITF1 is a transcription factor that is essential for the development of the brain, thyroid gland and lung. CASE REPORTS: We report on the clinical phenotype of a family with chorea, in which two sisters presented congenital hypothyroidism and one of them also had alveolar respiratory distress syndrome. A mutation was detected in TITF1 (c.825delC) in both of them and clinical improvement was observed in the response to treatment with low doses of levodopa-carbidopa. CONCLUSIONS: Chorea due to mutation of TITF1 is an underdiagnosed cause of chorea in children. Since it is possible to conduct a genetic diagnosis, we believe that performing it is always indicated in dominant familial cases, bearing in mind the variable penetrance, as well as in patients who present concomitant involvement of the lungs or hypothyroidism. Occasionally, it may be recommendable in cases of chorea with an unknown causation, which will enable us to avoid other tests, give a non-degenerative prognosis, offer genetic counselling and carry out more guided and effective therapeutic trials. For the time being, levodopa seems to be the preferred symptomatic treatment.

TITLE: Corea por mutacion de TITF1/NKX2-1: descripcion fenotipica y respuesta terapeutica en una familia.Introduccion. El corea por mutacion en el gen TITF1, tambien denominado corea hereditario benigno, es un trastorno autosomico dominante que suele iniciarse antes de los 5 anos. En la mayoria de casos, el corea tiende a mejorar con la edad. Puede asociar hipotiroidismo y problemas respiratorios, como el sindrome de distres respiratorio alveolar neonatal o la enfermedad pulmonar intersticial, ya que TITF1 es un factor de transcripcion esencial para el desarrollo del cerebro, tiroides y pulmon. Casos clinicos. Presentamos el fenotipo clinico de una familia con corea, en la cual dos hermanas presentan hipotiroidismo congenito, y una de ellas, sindrome de distres respiratorio alveolar. En ambas se identifico una mutacion en TITF1 (c.825delC) y se observo mejoria clinica en respuesta al tratamiento con levodopa-carbidopa en dosis bajas. Conclusiones. El corea por mutacion de TITF1 es una causa infradiagnosticada de corea en ninos. Debido a la posibilidad de realizar diagnostico genetico, creemos indicado realizarlo siempre en casos familiares dominantes, teniendo en cuenta la penetrancia variable, asi como en pacientes que presenten afectacion concomitante de pulmon o hipotiroidismo. En casos esporadicos, puede ser recomendable en coreas de causa no filiada, lo que nos permitira evitar otras pruebas, dar un pronostico no degenerativo, permitir un consejo genetico, y hacer ensayos terapeuticos mas dirigidos y eficaces. Por el momento, la levodopa parece el tratamiento sintomatico de eleccion.

[Clinical variability of polymicrogiria: report of 35 new cases and review of the literature]. / Variabilidad clínica de la polimicrogiria: a propósito de 35 nuevos casos y revisión de la bibliografía.

INTRODUCTION: The study of polymicrogyria with magnetic resonance imaging (MRI) has made possible the report of several series of patients in which the main clinical manifestations differ considerably. The aims of the study were to review the literature and to know the clinical variability of the patients attended in a neuropediatric service. PATIENTS AND METHODS: A retrospective study was conducted between 1989-2011 for the patients attended in our neuro-pediatric service and diagnosed of polymicrogyria by MRI. RESULTS: On the totality of 44 patients having polymicrogyria, 9 did not satisfy de inclusion criteria (Barkovich's radiological criteria). The polymicrogyria was bilateral in 22/35 patients (1 frontal, 22 perisylvian) and unilateral in 13/35 (2 frontal, the rest perisylvian). All patients with bilateral polymicrogyria had intellectual disability, 71% had global development delay, 75% had oromotor disorder and 40% had epilepsy. Patients with unilateral polymicrogyria had the following symptoms: 65% intellectual disability, 55% global development delay, 55% oromotor disorder, 55% epilepsy and 2 patients where free of symptoms (the oldest 2 year old). The initial symptoms were depending upon the age: the oromotor disorder was the most common in the newborn period, global development delay if the symptoms started before 2 years old and after 2 years epilepsy was the initial most common symptom. CONCLUSION: In our study the most common symptom was intellectual disability (independently of the type of poly-microgyria), followed by oromotor disorder and, with fewer proportion, epilepsy (in contrast with other series).

Variabilidad clínica de la polimicrogiria: a propósito de 35 nuevos casos y revisión de la bibliografía / Clinical variability of polymicrogiria: report of 35 new cases and review of the literatureepi

Introducción. El estudio diagnóstico de polimicrogiria mediante resonancia magnética ha facilitado la publicación de varias series de pacientes en las que las manifestaciones clínicas predominantes varían considerablemente. Objetivo. Conocer la variabilidad fenotípica de la polimicrogiria basándose en la serie de pacientes atendidos en nuestro servicio y la revisión de la bibliografía. Pacientes y métodos. Estudio retrospectivo de los pacientes diagnosticados de polimicrogiria mediante resonancia magnética y seguidos en consultas durante los años 1989-2011.Resultados. De un total de 44 pacientes, nueve fueron excluidos por no cumplir los criterios diagnósticos radiológicospropuestos por Barkovich. La polimicrogiria fue bilateral en 22/35 pacientes (una frontal, 21 perisilvianas) y unilateral en13/35 (dos frontales, el resto perisilvianas). Todos los pacientes con polimicrogiria bilateral tenían algún tipo de discapacidadintelectual, un 71% tenía retraso global del desarrollo, un 75% tenía trastorno oromotor y un 40% tenía epilepsia. Los pacientes con polimicrogiria unilateral presentaron discapacidad intelectual (65%), retraso global del desarrollo (55%), trastorno oromotor (55%) y epilepsia (55%), estando asintomáticos dos pacientes (2 años de edad). La presentación clínica de los pacientes dependía de la edad: en el período neonatal, el síntoma guía fue el trastorno oromotor; antes de los 2 años, el retraso global del desarrollo; y partir de los 2 años, la epilepsia. Conclusión. En este estudio, a diferencia de otras series, el síntoma más prevalente fue la discapacidad intelectual (independientemente del tipo de polimicrogiria), seguido del trastorno oromotor y, en menor medida, la epilepsia (AU)

Introduction. The study of polymicrogyria with magnetic resonance imaging (MRI) has made possible the report of severalseries of patients in which the main clinical manifestations differ considerably. The aims of the study were to review the literature and to know the clinical variability of the patients attended in a neuropediatric service. Patients and methods. A retrospective study was conducted between 1989-2011 for the patients attended in our neuropediatric service and diagnosed of polymicrogyria by MRI.Results. On the totality of 44 patients having polymicrogyria, 9 did not satisfy de inclusion criteria (Barkovich’s radiological criteria). The polymicrogyria was bilateral in 22/35 patients (1 frontal, 22 perisylvian) and unilateral in 13/35 (2 frontal, the rest perisylvian). All patients with bilateral polymicrogyria had intellectual disability, 71% had global development delay, 75% had oromotor disorder and 40% had epilepsy. Patients with unilateral polymicrogyria had the following symptoms: 65% intellectual disability, 55% global development delay, 55% oromotor disorder, 55% epilepsy and 2 patients wherefree of symptoms (the oldest 2 year old). The initial symptoms were depending upon the age: the oromotor disorder was the most common in the newborn period, global development delay if the symptoms started before 2 years old and after 2 years epilepsy was the initial most common symptom.Conclusion. In our study the most common symptom was intellectual disability (independently of the type of polymicrogyria), followed by oromotor disorder and, with fewer proportion, epilepsy (in contrast with other series) (AU)