RESUMEN
SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.
RESUMEN
INTRODUCTION: Patients with moderate-severe cerebral palsy require the support of their caregivers to carry out the activities of daily living (ADLs). OBJECTIVES: To describe the comorbidities, need for care in children with cerebral palsy and to analyse the influence of the degree of motor involvement, nutritional status and other neurological disorders. METHODS: Cross-sectional and observational study. Patients with cerebral palsy degrees III-IV-V according to the Gross Motor Function Classification System (GMFCS) have been studied. A record of comorbidities has been made and body composition has been studied using anthropometry and bioimpedance. In addition, a caregiver burden survey on ADLs has been carried out (10 items on the different actions: hygiene, clothing, transfers, sleeping and feeding). Which variables have the greatest influence on the perception of difficulty in performing ADLs have been studied. RESULTS: A total of 69 patients (50.7% women, mean age 10.46 ± 0.4 years) were analysed, with GMFCS grades: grade III 36.2% (N=25), grade IV 29.0% (N=20), grade V 34.8% (N=24). A relationship was found between the caregiver burden score and GMFCS grade (P=0.003) and intellectual disability (P<0.001). However, regardless of the degree of GMFCS and intellectual disability, there is greater difficulty in performing ADLs in relation to lower values in weight (Z-score) (P=0.028), fat mass (kg) (P=0.035), fat mass (%) (P=0.094), body mass index (Z-score) (P=0.086). CONCLUSIONS: In addition to the degree of clinical impairment, nutritional status is a factor that influences the caregiver's difficulty in performing the ADLs in cerebral palsy patients on which we can act to improve this problem.
Asunto(s)
Carga del Cuidador , Parálisis Cerebral , Estado Nutricional , Actividades Cotidianas , Parálisis Cerebral/fisiopatología , Parálisis Cerebral/terapia , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Cerebral palsy (CP) is the most frequent cause of motor disability in the paediatric age. The aim of this article is the study of the nutritional status of patients with CP followed-up in a reference hospital, as well as the relationship between neurological and nutritional state. MATERIAL AND METHODS: A cross-sectional, observational, descriptive and analytical study was conducted on a sample consisting of 4-15years old patients with CP with Gross Motor Function Classification System (GMFCS) gradesIII-IV-V, from a specialised paediatric hospital reference area. An interview (collection of general data, medications and nutritional habits), anthropometric study and bioimpedance (BIA) measurements were carried out. RESULTS: The study included 69 patients (recruitment 84.15%), with a mean age of 10.46±0.43years, and 50.7% females. The distribution according to GMFCS scale was: gradeIII (36.2%), gradeIV (29%), and gradeV (34.8%). According to weight for height: moderate malnutrition 21.8% (gradeV: 33.3%), severe malnutrition 5.8% (gradeV: 12.6%), overweight/obesity 23.2% (gradeIII: 24%, gradeIV: 35%). Adequate level of lean mass for height: gradeIII (36%), gradeIV (55%), and gradeV (16.7%). Fat excess: gradeIII (36%), gradeIV (40%), and gradeV (29.2%). Fat mass comparison: BIA 6.89±0.64kg versus anthropometry 5.56±4.43kg. CONCLUSIONS: In CP grade GMFCSV, the weight deficit associated with a decrease in lean body mass is common. Patients with CP grades GMFCSIII-IV have a significant prevalence of overweight/obesity. Anthropometry is a useful tool for nutritional assessment in children with CP, although fat levels could be underestimated.
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Parálisis Cerebral/fisiopatología , Desnutrición/etiología , Obesidad Infantil/etiología , Delgadez/etiología , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Desnutrición/diagnóstico , Desnutrición/epidemiología , Estado Nutricional , Obesidad Infantil/diagnóstico , Obesidad Infantil/epidemiología , Prevalencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Delgadez/diagnóstico , Delgadez/epidemiologíaRESUMEN
Bone health problems may be related to the nutritional deficit in pediatric patients with cerebral palsy. It is common to find asymptomatic vertebral fractures when they have low bone mineral density. Fat mass deficit could be related to a lower bone mineral density and a higher risk of vertebral fractures. OBJECTIVES: To study the bone health of patients with CP and its relationship with neurological and nutritional status. PURPOSE: Cerebral palsy (CP) is the most common cause of motor disability in pediatric age. METHODS: Cross-sectional, observational, descriptive, and analytical study in which patients with CP between 4 and 5 years with Gross Motor Function Classification System (GMFCS) grades III-IV-V were included. It was carried out: survey, anthropometric study, bioimpedanciometry (BIA), and bone densitometry. Patients with low bone mineral density (BMD Z score less than - 2.0) underwent lumbar radiography looking for vertebral fractures to be diagnosed with osteoporosis. RESULTS: Total sample: 51 patients (51.0% women). Mean age: 11.0 ± 0.5 years. BMD Z score average: - 2.1 (95% CI - 2.5, - 1.7). BMD Z score according to GMFCS: grade III - 1.6 (- 2.2; - 1.), grade IV - 1.6 (- 2.4; - 0.9), grade V - 3.1 (- 3.9, - 2.2) (p = 0.013). Bone health classification according to the International Society for Clinical Densitometry was: 47.1% normal, 52.9% low BMD. Relationship between low BMD and low fat mass (p = 0.030) and low cell mass (p = 0.040) was found. Prevalence of vertebral fractures in lumbar radiography: 25.9%, increasing as the degree of neurological involvement. Vertebral fractures were found in 5/13 GMFCS grade V, 2/6 GMFCS grade IV, and 0/10 GMFCS grade III. CONCLUSIONS: Bone health in the pediatric population with CP is compromised in relation to the degree of neurological involvement and nutritional status. Those patients with moderate-severe cerebral palsy and low BMD seem to present an increased risk of fracture.
Asunto(s)
Densidad Ósea/fisiología , Parálisis Cerebral/complicaciones , Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Parálisis Cerebral/epidemiología , Niño , Estudios Transversales , Personas con Discapacidad , Femenino , Fracturas Óseas/diagnóstico , Humanos , Masculino , Trastornos Motores/epidemiología , Trastornos Motores/etiología , Osteoporosis/epidemiologíaRESUMEN
PURPOSE: Rasmussen's encephalitis (RE) is a chronic neurological disorder characterized by inflammation of the cerebral cortex, mainly unilateral, that leads to drug-resistant epilepsy and progressive neurological impairment. Central Precocious Puberty (CPP) is uncommon, albeit increased in frequency in patients with neurological conditions and the physiopathological bases of these associations remains unclear in most cases. Epilepsy has been proposed to play a role, as well as the accumulation of substances produced as a result of metabolism or tissue degeneration in some neurodegenerative diseases. However, CPP has not been previously described in patients with RE. METHODS: From a series of patients affected by RE followed-up at a referral center, an in-depth review of the characteristics of those who developed CCP was carried out. RESULTS: Three cases were identified, representing a relative frequency of 21.4 % for CPP. They were girls, of Caucasian ethnicity, without family history of CPP or any image-identified abnormalities in the hypothalamic area. In two cases CPP manifested immediately before the onset of the epilepsy (prior to the diagnosis of RE) and in the other, after epilepsy onset but coinciding with a worsening of the seizures. A GnRH test with pubertal response confirmed CPP in the three cases. CONCLUSION: The high proportion of CPP in patients affected by RE suggested a plausible relationship between these two entities. Various factors involved, including neuroinflammation, are hypothesized in the present study. However, further studies are needed to elucidate the pathophysiological bases, which could provide insight in the understanding of both entities.
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Encefalitis/fisiopatología , Epilepsia/fisiopatología , Pubertad Precoz/fisiopatología , Convulsiones/fisiopatología , Niño , Preescolar , Epilepsia Refractaria/diagnóstico , Epilepsia Refractaria/fisiopatología , Electroencefalografía , Encefalitis/diagnóstico , Epilepsia/diagnóstico , Femenino , Humanos , Pubertad Precoz/diagnóstico , Convulsiones/diagnósticoRESUMEN
INTRODUCTION: We present our experience on idiopathic intracranial hypertension (IIH), before and after the introduction of a specific diagnosis and management protocol. METHOD: A descriptive retrospective study was conducted on patients with IIH over a 25year period (1990-2015), comparing the last 7years (after introduction of the protocol) with the previous 18years. RESULTS: Among the 18,865 patients evaluated, there were 54 cases of IIH (29 infants and 25 children). A comparison was made between the two time periods: 32 cases in 1990-2008 -published in An Pediatr (Barc). 2009;71:400-6-, and 23 cases in 2008-2015. In post-protocol period, there were 13 patients aged between 3-10months (62% males) with transient bulging fontanelle, and 10 aged between 2-14years (50% males), with papilloedema. A total of 54% of infants had recently finished corticosteroid treatment for bronchitis. In the older children, there was one case associated with venous thrombosis caused by otomastoiditis, one case on corticosteroid treatment for angioma, and another case treated with growth hormone. Transfontanelle ultrasound was performed on all infants, and CT, MRI and angio-MRI was performed on every child. Lumbar puncture was performed on 2 infants in whom meningitis was suspected, and in all children. All patients progressed favourably, with treatment being started in 3 of them. One patient relapsed. DISCUSSION: Characteristics and outcomes of patients overlap every year. IIH usually has a favourable outcome, although it may be longer in children than in infants. It can cause serious visual disturbances, so close ophthalmological control is necessary. The protocol is useful to ease diagnostic decisions, monitoring, and treatment.
Asunto(s)
Seudotumor Cerebral/diagnóstico , Seudotumor Cerebral/terapia , Adolescente , Algoritmos , Niño , Preescolar , Protocolos Clínicos , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Factores de TiempoRESUMEN
OBJECTIVE: A study of epilepsy, according to the age at onset of the crisis and its causes, monitored by a Paediatric Neurology Unit over a period of three years. PATIENTS AND METHODS: Historical cohorts study was conducted by reviewing the Paediatric Neurology medical records data base of epileptic children followed-up from 1 January 2008 to 31 December 2010. RESULTS: A total of 4,595 children were attended during the study period. The diagnosis of epilepsy was established in 605 (13.17%): 277 (45.79%) symptomatic, 156 (25.79%) idiopathic, and 172 (28.43%) with cryptogenic epilepsy. Absence epilepsy and benign childhood epilepsy with centro-temporal spikes are the idiopathic epileptic syndromes most prevalent, and the most prevalent symptomatic epilepsies are prenatal encephalopathies. More than one-quarter (26.12%) of epilepsies began in the first year of life, and 67.72% were symptomatic. Refractory epilepsy was observed in 25.29%, 42.46% with cognitive impairment, 26.45% with motor involvement, and 9.92% with an autism spectrum disorder, being more frequent at an earlier age of onset. CONCLUSIONS: The absence of a universally accepted classification of epileptic syndromes makes tasks like this difficult, starting with the terminology. A useful classification would be aetiological, with two groups: a large group with established aetiology, or very likely genetic syndromes, and another with no established cause. The age of onset of epilepsy in each aetiological group helps in the prognosis, which is worsened by refractoriness and associated neurodevelopmental disorders, and are generally worse at an earlier onset and in certain aetiologies.
Asunto(s)
Epilepsia/clasificación , Adolescente , Edad de Inicio , Niño , Preescolar , Epilepsia/etiología , Síndromes Epilépticos/clasificación , Síndromes Epilépticos/etiología , Femenino , Unidades Hospitalarias , Humanos , Lactante , Masculino , Neurología , Pediatría , Factores de TiempoRESUMEN
AIM: To analyze the factors involved in the prognosis of symptomatic epilepsies in relation to their age at onset, monitored at a neuropediatric section of regional reference over a period of three years. PATIENTS AND METHODS: Children diagnosed with symptomatic epilepsy, supervised from January 1, 2008 to December 31, 2010, collecting epidemiological, clinical and developmental data. RESULTS: Of the 4595 children attended during the period, the diagnosis of epilepsy was established at 605 (13.17%): 277 (45.79%) symptomatic epilepsies. Symptomatic etiology predomininates in epileptic patients that started below one year of age, 67.72%, and between 1-3 years, 61.39%. 37.54% of symptomatic epilepsy is refractory, 72.92% have cognitive impairment, 55.23% have motor impairment and 17.32% have autism spectrum disorder. The younger the patient, the higher the percentage of refractoriness and display of any neurological or associated development impact. Some etiologies have higher rates of refractoriness. CONCLUSIONS: A useful classification would be etiological, with two groups: a large group with established etiology or very likely genetic syndromes and another with no established cause. The age of onset of epilepsy in each etiological group adds prognostic orientation. Prognosis of epilepsy is overshadowed by refractoriness and associated neurodevelopmental disorders, which are generally worse at an earlier onset and in certain etiologies.
TITLE: Pronostico de las epilepsias sintomaticas segun la edad de inicio, controladas durante tres años en una unidad de neuropediatria de referencia regional.Objetivo. Analizar los factores implicados en el pronostico de las epilepsias sintomaticas en relacion con su edad de inicio, controladas en una unidad de neuropediatria de referencia regional durante tres años. Pacientes y metodos. Revision de los pacientes con diagnostico de epilepsia sintomatica, controlados desde el 1 de enero de 2008 hasta el 31 de diciembre de 2010, recogiendo datos epidemiologicos, clinicos y evolutivos. Resultados. Del total de 4.595 niños atendidos en el periodo, se establecio el diagnostico de epilepsia en 605 (13,17%), de las cuales 277 (45,79%) son epilepsias sintomaticas. En los pacientes que iniciaron la epilepsia por debajo del año de vida predominan las de etiologia sintomatica (67,72%), y tambien entre 1-3 años (61,39%). El 37,54% de las epilepsias sintomaticas son refractarias, el 72,92% asocian un deficit cognitivo, el 55,23%, alguna afectacion motora, y el 17,32%, algun trastorno del espectro autista. A menor edad, mayor porcentaje de refractariedad y de presentar alguna repercusion neurologica o del desarrollo asociada. Algunas etiologias tienen mayores tasas de refractariedad. Conclusiones. Una clasificacion util de la epilepsia es la etiologica, con dos grupos: un gran grupo con las etiologias establecidas o sindromes geneticos muy probables, y otro de casos sin causa establecida. La edad de inicio de la epilepsia en cada grupo etiologico añade orientacion pronostica. El pronostico lo ensombrecen la refractariedad y las alteraciones asociadas del neurodesarrollo, y es peor, en general, cuanto mas precoz es el inicio y en etiologias concretas.
Asunto(s)
Epilepsia/terapia , Adolescente , Edad de Inicio , Niño , Preescolar , Epilepsia/diagnóstico , Femenino , Humanos , Lactante , Masculino , Pronóstico , Estudios Retrospectivos , Factores de TiempoRESUMEN
INTRODUCTION: The dynamic increase in the number of triplet repeats of cytosine-guanine-guanine (CGG) in the FMR1 gene mutation is responsible for three OMIM syndromes with a distinct clinical phenotype: Fragile X syndrome (FXS) and two pathologies in adult carriers of the premutation (55-200 CGG repeats): Primary ovarian insufficiency (FXPOI) and tremor-ataxia syndrome (FXTAS) associated with FXS. CLINICAL OBSERVATION AND METHODS: CGG mutation dynamics of the FMR1 gene were studied in DNA samples from peripheral blood from the index case and other relatives of first, second and third degree by TP-PCR, and the percentage methylation. RESULTS: Diagnosis of FXS was confirmed in three patients (21.4%), eight patients (57.1%) were confirmed in the premutation range transmitters, one male patient with full mutation/permutation mosaicism (7.1%) and two patients (14.3%) with normal study. Of the eight permutated patients, three had FXPOI and one male patient had FXTAS. DISCUSSION: Our study suggests the importance of making an early diagnosis of SXF in order to carry out a family study and genetic counselling, which allow the identification of new cases or premutated patients with FMR1 gene- associated syndromes (FXTAS, FXPOI).
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Ataxia/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Insuficiencia Ovárica Primaria/genética , Temblor/genética , Repeticiones de Trinucleótidos , Adolescente , Adulto , Anciano , Ataxia/diagnóstico , Niño , Preescolar , Femenino , Síndrome del Cromosoma X Frágil/diagnóstico , Marcadores Genéticos , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Mutación , Insuficiencia Ovárica Primaria/diagnóstico , Temblor/diagnósticoRESUMEN
AIM: To analyze the factors involved in the prognosis of non-symptomatic epilepsy (idiopathic and cryptogenic) in relation to their age of onset, monitored at a regional section of Neuropediatry reference over a period of three years. PATIENTS AND METHODS: Patients with diagnosis of non-symptomatic epilepsy supervised from January 1, 2008 to December 31, 2010, collecting epidemiological, clinical, complementary examinations and developmental data. RESULTS: Of the 4595 children attended during the period, the diagnosis of epilepsy was established in 605 (13.17%): 156 (25.79%) idiopathic epilepsies and 172 (28.43%) cryptogenic epilepsies. 15.7% of cryptogenic epilepsies and 14.1% of idiopathic epilepsies are refractory to treatment. Some epileptic syndromes, such as reflex epilepsies, Dravet syndrome, Ohtahara syndrome or Lennox-Gastaut syndrome, have higher rates of drug resistance. 84.62% of idiopathic epilepsies and 79.77% of cryptogenic epilepsies present no other associated neurological disorder. CONCLUSIONS: A useful classification would be etiological, with two groups: a large group with established etiology or very likely genetic syndromes and another with no established cause. The age of onset of epilepsy in each etiological group adds prognostic orientation. Prognosis of epilepsy is worsened by refractoriness and associated neurodevelopmental disorders, and are generally worse at an earlier onset and in certain etiologies.
TITLE: Pronostico de las epilepsias no sintomaticas segun la edad de inicio, controladas durante tres años en una unidad de neuropediatria de referencia regional.Objetivo. Analizar los factores implicados en el pronostico de las epilepsias no sintomaticas (idiopaticas y criptogenicas) en relacion con su edad de inicio, controladas en una unidad de neuropediatria de referencia regional durante un periodo de tres años. Pacientes y metodos. Analisis de los pacientes con diagnostico de epilepsia no sintomatica, controlados desde el 1 de enero de 2008 hasta el 31 de diciembre de 2010, recogiendo datos epidemiologicos, clinicos, examenes complementarios y datos evolutivos. Resultados. Del total de 4.595 niños atendidos en el periodo, se establecio el diagnostico de epilepsia en 605 (13,17%), de las cuales 156 (25,79%) fueron epilepsias idiopaticas, y 172 (28,43%), criptogenicas. El 15,7% de las epilepsias criptogenicas y el 14,1% de las idiopaticas son refractarias al tratamiento. Algunos sindromes epilepticos, como las epilepsias reflejas, el sindrome de Dravet, el sindrome de Ohtahara o el sindrome de Lennox-Gastaut, tienen mayores tasas de farmacorresistencia. No presentan otra alteracion neurologica asociada el 84,62% de las epilepsias idiopaticas y el 79,77% de las epilepsias criptogenicas. Conclusiones. Una clasificacion util de la epilepsia es la etiologica, con dos grupos: un gran grupo con las etiologias establecidas o sindromes geneticos muy probables y otro de casos sin causa establecida. La edad de inicio de la epilepsia en cada grupo etiologico añade orientacion pronostica. El pronostico lo ensombrecen la refractariedad y las alteraciones asociadas del neurodesarrollo, y es peor, en general, cuanto mas precoz sea el inicio y en etiologias concretas.
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Epilepsia/epidemiología , Adolescente , Edad de Inicio , Trastorno del Espectro Autista/epidemiología , Niño , Preescolar , Comorbilidad , Discapacidades del Desarrollo/epidemiología , Epilepsia Refractaria/epidemiología , Epilepsia Refractaria/terapia , Epilepsia/etiología , Epilepsia/genética , Epilepsia/terapia , Femenino , Humanos , Lactante , Discapacidad Intelectual/epidemiología , Masculino , Trastornos del Movimiento/epidemiología , Pronóstico , Estudios Retrospectivos , España/epidemiología , Síndrome , Resultado del TratamientoRESUMEN
INTRODUCTION: Aicardi-Goutieres syndrome is a rare immune disorder due to mutations in seven different genes that encode proteins called TREX1, ribonuclease H2 complex, SAMHD1, ADAR and IDIH1 (MDA5), which are involved in acid nucleic metabolism. Two cases are described in detail below caused by RNASEH2B gene mutation, one of which displays a mutation no described to date. CASE REPORTS: Case 1: male consulting because from 5-month-old shows loss of maturity items acquired until then, coming with several fever episodes. Case 2: a 4-month-old boy showing since 2-month-old great irritability and oral-feeding trouble with severe psychomotor impairment. In both cases it was found an increase of pterines in the cerebrospinal fluid, mainly neopterine, with calcifications in the basal ganglia. The diagnosis was proved by sequencing RNASEH2B gene, founding in case 2 a new mutation not described previously. CONCLUSIONS: The reported cases belong to the description already done by Aicardi-Goutieres, it should be noticed this syndrome in a patient with a subacute encephalopathy of debut in the first year of life, dystonia/spasticity in variable degree and important affectation/regression of psychomotor development, particularly in those with increase of pterines (neopterine) in the cerebrospinal fluid and calcifications in the basal ganglia.
TITLE: Variaciones fenotipicas en el sindrome de Aicardi-Goutieres causado por mutaciones en el gen RNASEH2B: presentacion de dos nuevos casos.Introduccion. El sindrome de Aicardi-Goutieres es un trastorno inmunitario raro debido a mutaciones en siete genes que codifican proteinas llamadas TREX1, el complejo ribonucleasa H2, SAMHD1, ADAR e IFIH1 (MAD5), las cuales estan implicadas en el metabolismo de los acidos nucleicos. A continuacion se presentan dos nuevos casos por mutacion en el gen RNASEH2B, uno de los cuales presenta una mutacion no descrita hasta la fecha. Casos clinicos. Caso 1: varon que consulto porque desde los 5 meses, coincidiendo con cuadros febriles de repeticion, presentaba perdida de los items madurativos adquiridos hasta la fecha. Caso 2: niño de 4 meses que desde los 2 meses mostraba gran irritabilidad con dificultades en la alimentacion, asociado a un grave retraso psicomotor. En ambos casos se constato un aumento de las pterinas en el liquido cefalorraquideo, principalmente de la neopterina, con calcificaciones en los ganglios basales. El diagnostico se confirmo mediante secuenciacion del gen RNASEH2B; el caso 2 presentaba una mutacion no descrita en la literatura medica. Conclusiones. Los casos corresponden a la descripcion clasica realizada por Aicardi-Goutieres. Debe tenerse en cuenta este sindrome ante un paciente con un cuadro de encefalopatia subaguda de comienzo en el primer año de vida, distonia/espasticidad en grado variable e importante afectacion/regresion del desarrollo psicomotor, especialmente si asocia aumento de las pterinas (neopterina) en el liquido cefalorraquideo y calcificaciones en los ganglios basales.
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Enfermedades Autoinmunes del Sistema Nervioso/genética , Mutación Missense , Malformaciones del Sistema Nervioso/genética , Ribonucleasa H/genética , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico por imagen , Enfermedades Autoinmunes del Sistema Nervioso/enzimología , Ganglios Basales/diagnóstico por imagen , Ganglios Basales/patología , Biopterinas/líquido cefalorraquídeo , Calcinosis/etiología , Calcinosis/patología , Trastornos de Ingestión y Alimentación en la Niñez/genética , Estudios de Asociación Genética , Heterocigoto , Humanos , Lactante , Discapacidad Intelectual/genética , Imagen por Resonancia Magnética , Masculino , Espasticidad Muscular/genética , Neopterin/líquido cefalorraquídeo , Malformaciones del Sistema Nervioso/diagnóstico por imagen , Malformaciones del Sistema Nervioso/enzimología , Neuroimagen , Fenotipo , Ribonucleasa H/deficiencia , Análisis de Secuencia de ADNRESUMEN
INTRODUCTION: Legius syndrome is an autosomal dominant disorder caused by the mutation in the SPRED1 gene involving a negative regulator of the RAS-MAPK pathway, similar to neurofibromin and therefore shows some clinical similarities to neurofibromatosis type I (NF1) but less severe. These patients have multiple cafe-au-lait spots, sometimes associated with skin fold freckling, dysmorphic features, lipomas, and mild learning disabilities. However, this syndrome is not associated with neurofibromas, optic gliomas, Lisch nodules or tumor predisposition. CASE REPORT: We present a 10 months child, without a personal interest history, consulting by hypotonic extremities, cafe-au-lait spots and mild psychomotor difficult. Mother's sister and grandfather have some cafe-au-lait spots. In our patient, NF1 genetic study was negative, but we observe a mutation in the SPRED1 gene, compatible with Legius syndrome. Asymptomatic mother shows the same mutation in SPRED1 gene. CONCLUSION: We emphasize the relevance of the differential diagnosis of NF1 with respect to numerous complications to appear, with a better prognosis recently described entity as it is Legius syndrome.
TITLE: Un nuevo sindrome neurocutaneo: sindrome de Legius. A proposito de un caso.Introduccion. El sindrome de Legius es un trastorno autosomico dominante resultante de la mutacion del gen SPRED1, que implica perdida de funcion de una de las proteinas implicada en la via patogenica RAS-MAPK, similar a la neurofibromina y por ello muestra similitudes clinicas con la neurofibromatosis tipo 1 (NF1), pero con menor gravedad. Estos pacientes presentan multiples manchas cafe con leche y pueden asociar efelides, rasgos dismorficos, lipomas y trastornos del aprendizaje sin relacionarse con la aparicion de neurofibromas, gliomas opticos, nodulos de Lisch o predisposicion tumoral. Caso clinico. Niño de 10 meses, sin antecedentes personales de interes, que consulta por hipotonia de extremidades, manchas cafe con leche y leve retraso psicomotor. En los antecedentes familiares destaca una hermana de la madre y el abuelo materno con manchas cafe con leche. En nuestro paciente, el estudio genetico fue negativo para NF1, pero se hallo una mutacion en el gen SPRED1, compatible con el sindrome de Legius. La madre asintomatica presenta la misma mutacion en el gen SPRED1. Conclusion. Es de destacar la importancia del diagnostico diferencial de NF1, con las numerosas complicaciones que puede conllevar, con una entidad recientemente descrita de mejor pronostico como es el sindrome de Legius.
Asunto(s)
Manchas Café con Leche/diagnóstico , Humanos , Lactante , MasculinoRESUMEN
INTRODUCTION: Mesial temporal sclerosis (MTS) is defined as neuron loss and gliosis in the hippocampus and adjacent structures. Here we report on our 19 years' experience in dealing with this condition. PATIENTS AND METHODS: A retrospective, descriptive study was conducted of patients diagnosed with MTS between May 1990 and January 2009. RESULTS: A diagnosis of MTS was established in 16 cases (62.5% males). By location these cases were distributed as follows: 12 were unilateral (seven left temporal and five right) and four were bilateral. It was associated to cortical dysplasia in six patients (37.5%) and to hippocampal arachnoid cysts in two other cases. As regards possible causations, in one case herpes simplex encephalitis was suspected; in three cases, a prenatal cerebral vascular pathology; and in three others, prenatal infection by cytomegalovirus. The distribution of the clinical spectrum was as follows: five patients with isolated clinical epilepsy; one with isolated psychomotor retardation or mental retardation (PMR-MR); one with isolated autism spectrum disorder (ASD); three with epilepsy associated to PMR-MR; one with epilepsy associated to ASD; two with PMR-MR and ASD; and two with the triad consisting of epilepsy together with PMR-MR and ASD. In one case, MTS was discovered in migraine studies, without any other symptoms. Crises were controlled with monotherapy in all the patients who received antiepileptic treatment except in three, one of whom required surgery. CONCLUSIONS: The definitive diagnosis of MTS is pathologic, but the latest neuroimaging techniques have allowed a very reliable approximate diagnosis to be reached. It may be associated to other malformative disorders, such as focal cortical dysplasia or cysts. MTS can be observed in epilepsy (whether refractory or not), but also in ASD, PMR-MR or asymptomatic patients.
Asunto(s)
Hipocampo/patología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Estudios Retrospectivos , Esclerosis/diagnóstico , Factores de TiempoRESUMEN
PATIENTS AND METHODS: This study reviews our experience over the last 18 years with paediatric patients diagnosed with non-haemorrhagic cerebrovascular accidents (CVA) after the perinatal period. Data were collected for the period between May 1990 and May 2008 (n = 10 270 children) and special attention was given to cases with no previous pathology. RESULTS: We found 41 cases that were diagnosed with post-natal non-haemorrhagic CVA, of which 13 did not present any known pathology at the onset of the symptoms. Nine patients were diagnosed as having ischaemic CVA (ICVA), three cases had thrombosis of the venous sinuses and there was one case of haemorrhagic infarction (HI). No causation was found in five cases, three of which were heterozygotic for the C677T mutation of methylenetetrahydrofolate reductase. ICVA was caused by fibromuscular dysplasia, aneurysm of the auricular septum and patent foramen ovale, homocystinuria and chickenpox. A recent ear infection and diminished levels of protein C were noted in two cases of venous thrombosis. Five patients with ICVA and the case of HI were treated with oral antiaggregants, anticoagulants were administered in two of the thromboses, and the remaining cases did not receive any treatment. Seven patients (four ICVA, two thromboses and the HI) did not present any kind of sequelae, four ICVA presented different degrees of hemiparesis and two died (one ICVA and one thrombosis). CONCLUSIONS: The scarcity of studies and therapeutic clinical trials in the paediatric age makes it difficult to lay down clear guidelines of conduct, especially from the therapeutic point of view. The different specialists involved must collaborate with each other.