[Update on the treatment of RASopathies]. / Actualizacion del tratamiento de las rasopatias.

INTRODUCTION: The term 'RASopathies' covers a series of diseases that present mutations in the genes that code for the proteins of the RAS/MAPK pathway. These diseases include neurofibromatosis type 1, Noonan syndrome, Legius syndrome, LEOPARD syndrome, Costello syndrome and cardiofaciocutaneous syndrome. Involvement of the RAS/MAPK pathway not only increases predisposition to develop tumours, but also determines the presence of phenotypic anomalies and alterations in learning processes. AIM: To review the use of therapeutic strategies with mechanisms that have a selective action on RASopathies. DEVELOPMENT: The fact that the RAS pathway is involved in a third of all neoplasms has led to the development and study of different drugs at this level. Some of these pharmaceutical agents have been tested in RASopathies, mainly in neurofibromatosis type 1. Here we analyse the use of different antitarget treatments: drugs that act on the membrane receptors, such as tyrosine kinase inhibitors, in the mTOR pathway or MEK inhibitors. These latter have shown potential benefits in recent studies conducted on different RASopathies. CONCLUSIONS: Today, thanks to the results from the first studies conducted with MEK inhibitor based mainly on animal models, a number of promising clinical trials are being carried out.

TITLE: Actualizacion del tratamiento de las rasopatias.Introduccion. El termino 'rasopatias' agrupa una serie de enfermedades que presentan mutaciones en genes que codifican las proteinas de la via RAS/MAPK. Estas enfermedades incluyen la neurofibromatosis de tipo 1, el sindrome de Noonan, el sindrome de Legius, el sindrome LEOPARD, el sindrome de Costello y el sindrome cardiofaciocutaneo. La afectacion de la via RAS/MAPK no solo aumenta la predisposicion a desarrollar tumores, sino que tambien determina la presencia de anomalias fenotipicas y alteraciones en los procesos de aprendizaje. Objetivo. Revisar el papel del uso de estrategias terapeuticas con mecanismos de accion selectivo en las rasopatias. Desarrollo. El hecho de que la via RAS participe en un tercio de las neoplasias ha motivado el desarrollo y el estudio de distintos farmacos a este nivel. Algunos de estos farmacos han sido probados en las rasopatias, principalmente en la neurofibromatosis de tipo 1. Analizamos el uso de distintos tratamientos antidiana: farmacos que actuan en los receptores de membrana, como los inhibidores de la tirosincinasa, en la via mTOR o los inhibidores de MEK. Existe un potencial beneficio de estos ultimos en estudios recientes realizados en distintas rasopatias. Conclusiones. Actualmente, gracias a los resultados de los primeros trabajos desarrollados con inhibidor de MEK basados principalmente en modelos animales, se estan realizando multiples ensayos clinicos prometedores.

10-year outcome of children born with anorectal malformation, treated by posterior sagittal anorectoplasty, assessed according to the Krickenbeck classification.

BACKGROUND: Anorectal malformations (ARMs) affect 1 in 4000 to 5000 births. The Krickenbeck conference developed a classification based on anatomical and functional criteria to better compare treatment outcome. AIM: The aim of this study is to evaluate the functional outcome in patients 10 years following standardized surgical treatment of ARM related to the Krickenbeck classification. . METHODS: Anatomical anomalies were classified as above. Children and carers were followed closely in a multidisciplinary clinic. Data were collected using a functional outcome questionnaire for a minimum of 10 years after surgical reconstruction. Outcome measurements were related to the Krickenbeck classification. RESULTS: There were 53 children in the study group (29 male, 24 female). Krickenbeck anatomy: perineal fistula, 36%; vestibular fistula, 26%; rectourethral fistula, 36%; rectovesical fistula, 2%. All children were treated by posterior sagittal anorectoplasty. In children with perineal fistula, continence was achieved in 90%. Grade 2 constipation was noted in 21%. One child had a Malone antegrade continence enema (MACE) procedure. In children with vestibular fistula, continence was achieved in 57%. Grade 3 constipation was noted in 28%. One child had grade 1, and one child had grade 2 soiling. Two children had a MACE procedure. In children with rectourethral fistula, continence was achieved in 58%. One child had grade 3 soiling. Grade 3 constipation was found in 42% of children and grade 2 constipation in 1 child. A MACE procedure was performed in 36%. The only child with a bladder neck fistula had a MACE procedure for intractable soiling. CONCLUSIONS: The outcome for patients with ARM is related to the severity of the anomaly. The uniform application of the Krickenbeck classification should allow rational comparison of treatment outcome.

Trastornos oromotores en una unidad de neurología pediátrica. Clasificación y evolución clínica / Oromotor disorders in a paediatric neurology unit their classification and clinical course

Introducción. El concepto ‘trastornos oromotores’ engloba al conjunto de enfermedades que afectan de forma predominante a las estructuras que intervienen en la movilidad facial y orofaríngea, y que son imprescindibles para una correcta mecánica de la alimentación y para la articulación del lenguaje y la expresividad facial. La alteración de estas funcionespuede afectar significativamente a la calidad de vida y a la integración social de estos pacientes. Pacientes y métodos. Estudio descriptivo retrospectivo de 64 pacientes diagnosticados de trastornos oromotores, controlados en el Servicio de Neurología Pediátrica del Hospital Universitari Vall d’Hebron. De cada uno de ellos, detallamos: etiología, edad de presentación, información acerca del trastorno de la alimentación, de la articulación del lenguaje y de posibles manifestaciones asociadas, y evolución durante el período de seguimiento de los diferentes aspectos clínicos. Resultados. La revisión de la casuística delservicio nos ha permitido clasificar a los enfermos afectos de trastornos oromotores en función de la localización de la lesión y su enfermedad de base, distribuyéndolos en cuatro grupos principales: pacientes con síndromes polimalformativos, con afectación cortical perisilviana, con disgenesia troncoencefálica y con afectación del sistema nervioso periférico. Conclusiones. La clasificación de los pacientes afectos de trastornos oromotores y el estudio de la evolución natural de cada uno de los grupos facilitan el abordaje y permiten optimizar el manejo y realizar una prevención adecuada de las posibles complicaciones de este tipo de pacientes

Introduction. The term ‘oro-motor disorders’ refers to a group of diseases that predominantly affect sensory inputs, motor systems and movement organization involved in sucking, chewing, swallowing, speech articulation and facial nonverbal communication. Loss of any of the aforementioned functions results in poor social integration and significant quality of life reduction. Patients and methods. Retrospective, observational study of 64 patients with oro-motor disorders diagnosed andfollowed-up at the Child Neurology Service of Vall d’Hebron University Hospital. The oro-motor disorder cause, age at the beginning of symptoms, type of feeding difficulties, type of speech disorders and other associated clinical manifestations were investigated in all patients. Changes in clinical manifestations throughout the period of follow-up in this cohort wereanalyzed as well. Results. Classification of oro-motor disorders in childhood can be achieved combining the etiology and the anatomical location of the underlying disease. Four main groups can be distinguished: due to dysmorphological syndromes; secondary to bilateral perisylvian cortical dysplasias; due to brainstem dysgenesis, and secondary to congenital musculardiseases. Conclusions. Establishing the origin, nervous system location and pathophysiology of diseases leading to oro-motor disorders provides clues to natural history and permits anticipation in terms of treatment and care provision

Clinical and electrophysiological characteristics in children with atrioventricular nodal reentrant tachycardia.

Atrioventricular (AV) nodal reentrant tachycardia is one of the most common supraventricular tachycardias in childhood. However, information about AV nodal reentrant tachycardia in childhood is limited, especially about the variant and multiple forms. The purpose of this retrospective study was to investigate the clinical and electrophysiological characteristics in pediatric patients with AV nodal reentrant tachycardia. Forty-eight pediatric patients with AV nodal reentrant tachycardia were included (ages 11-18 years; 25 males and 23 females). The age of onset and duration of symptoms were significantly younger and shorter in pediatric patients, respectively. A higher incidence of antegrade dual AV nodal pathways was found in adult patients than pediatric patients (72.9 vs 52.1% p = 0.003). Both antegrade and retrograde slow pathway functions were better in pediatric than adult patients. There was no significant difference between children and adults in the occurrence of variant and multiple forms of AV nodal reentrant tachycardia. This study demonstrated that pediatric patients have different electrophysiologic characteristics from those of adult patients.

Twin fetuses with abnormalities that overlap with three midline malformation complexes.

Twin fetuses aborted at an estimated gestational age of 145 days were concordant for oral, facial, skeletal, and central nervous system malformations. The twins were discordant for other anomalies including cardiac defects, polydactyly, and malrotated short bowel. The combination of malformations observed overlaps with that of the oral-facial-digital syndrome, hydrolethalus syndrome, and Pallister-Hall syndrome. The problem of phenotypic overlap between these syndromes is discussed.