Identification of a somatic mutation in the RHEB gene through high depth and ultra-high depth next generation sequencing in a patient with Hemimegalencephaly and drug resistant Epilepsy.

Malformations of cortical development are a frequent cause of drug-resistant Epilepsy and developmental delay. Hemimegalencephaly is a Malformation of cortical development characterized by enlargement of all or a part of one cerebral hemisphere. Germline and somatic mutation in genes belonging to the Mammalian Target of Rapamycin (mTOR) pathway has been identified in patients suffering from epilepsy secondary to Hemimegalencephaly and focal cortical dysplasia. We present here a patient suffering from severe neonatal Epilepsy since 3 h of life secondary to Hemimegalencephaly, requiring an anatomic hemispherectomy surgical procedure for seizure control, where by means of next-generation sequencing at an ultra-high depth coverage, we were able to identify a novel somatic mutation in the RHEB gene (NM_005614: c.119A > T: p. Glu40Val). The histopathological diagnosis was Cortical Dysplasia type IIB determined by the presence of dysmorphic neurons of variable size with nuclear alteration and balloon cells in the context of Hemimegalencephaly, which are similar to that have been demonstrated in hyperactivating RHEB models. This is the first report of a somatic mutation in RHEB gene in a patient suffering from Epilepsy secondary to Hemimegalencephaly. It highlights different current topics in the fields of genetics of Malformations of cortical development: a-somatic mosaicism is not uncommon in these neurodevelopmental disorders; b-the molecular diagnostic approach should involve the use of state-of-the-art methods and the sampling of different tissues; c-new findings might facilitate therapeutics discoveries while providing an improved understanding of normal brain development.

Síndrome del dolor regional complejo / Complex regional pain syndrome

El síndrome de dolor regional complejo (SDRC) es una neuropatía crónica dolorosa progresiva con disfunción del sistema nervioso autónomo, desmineralizacion ósea y debilidad muscular; cuya aparición se asocia a algún evento traumático (fractura, cirugía o evento cardiovascular, etc.). Su diagnostico es fundamentalmente por interrogatorio y examen físico y se basa en el reconocimiento de algunas de las tres etapas clínicas clásicamente descriptas, predominando en las tempranas el dolor y los cambios autonómicos, y en las tardías, la atrofia y la pérdida de la funcionalidad. El pronóstico de la enfermedad es mejor cuando el diagnóstico es precoz (ej. durante la primera etapa) lo que minimiza las secuelas en el largo plazo. El tratamiento es interdisciplinario, siendo clave proporcionar alivio al dolor y la participación de personal entrenado en rehabilitación neuromuscular y/u ocupacional, con el objetivo de preservar y recuperar la funcionalidad perdida.