[FOXG1, a new gene responsible for the congenital form of Rett syndrome]. / FOXG1, un nuevo gen responsable de la forma congenita del sindrome de Rett.

INTRODUCTION: Rett syndrome (RS) is a neurodevelopmental disorder that affects girls almost exclusively. The identification of mutations in the MECP2 and CDKL5 genes offers genetic confirmation of the clinical diagnosis. The FOXG1 gene appears to be a novel cause of the congenital variant of RS. CASE REPORT: We describe the first Spanish patient with the atypical (congenital) variant of RS with mutation of the FOXG1 gene and the case is compared with 12 patients previously reported in the literature; clinical criteria that suggest alterations in FOXG1 are proposed. The patient was referred at the age of 6 months due to overall retardation, axial hypotonia, microcephaly and a peculiar phenotype. Magnetic resonance imaging of the brain revealed hypoplasia of the corpus callosum, frontal atrophy and ventriculomegaly. The appearance of hand-to-mouth stereotypic movements at 12 months pointed the clinical diagnosis towards an atypical variant of RS, the congenital form; there was progressive improvement of visual contact and interest in her surroundings. Frequent respiratory infections and obstructive sleep apnoea syndrome. At the age of 5 years there was partial control over the axial tone, grasping with the hands, good contact and babbling, without epilepsy or behavioural disorders. The MECP2 and subtelomeric deletion study did not reveal any alterations; two polymorphisms were identified in the CDKL5 gene and a pathogenic mutation was found in FOXG1 (c.624C>G p.Tyr203X). CONCLUSIONS: It has been shown that 92% of patients with mutations in the FOXG1 gene present the congenital form of RS with severe generalised hypotonia, early acquired microcephaly (-3 to -6 standard deviations) and peculiar phenotype. When faced with a diagnosis of RS with no alterations in the MECP2 and CDKL5 genes, especially in the case of the congenital variant, the FOXG1 gene must be investigated. The molecular diagnosis confirms the clinical diagnosis and provides the family with genetic counselling.

[Neurologic presentation in haemolytic-uraemic syndrome]. / Manifestaciones neurológicas en el síndrome hemolítico urémico.

INTRODUCTION: Haemolytic-uraemic syndrome (HUS) is characterized by microangiopathic hemolytic anaemia, thrombopenia and multiorganic aggression, specially renal, gastrointestinal and central nervous system disturbances. Sporadic in Spain (2/1,500,000 inhabitants), its clinical onset includes acute renal failure, hypertension and central nervous system symptoms (irritability, drowsiness, convulsions, cortical blindness, hemiparesia or coma), due to metabolic distress, hypertension or central nervous system microangiopathy. Few long-term outcome studies have been published. PATIENTS AND METHODS: A retrospective analysis of a series of 58 patients with HUS between 1981 and 2006, is reported. Clinical onset, laboratory, electrophysiology, neuroimaging tests, and prognosis factors are reviewed, together with long-term clinical outcome. RESULTS: 22 children presented neurologic symptoms, seven had some neurological test; one patient died; in five some neurological sequelae persisted (hemiparesia, cognitive deficit, visual-perception deficit), the other 16 remaining asymptomatic. CONCLUSIONS: Neurological morbility is high in HUS (27% of the children with neurological symptoms), with a 1.7% mortality. Seizure at onset was not a poor prognosis factor in our group. No positive correlation can be established between neuroimaging and long-term outcome.

Manifestaciones neurológicas en el síndrome hemolítico urémico / Neurologic presentation in haemolytic uraemic syndrome

Introducción. El síndrome hemolítico urémico (SHU) se define como anemia hemolítica microangiopática, trombopenia y daño multiparenquimatoso fundamentalmente renal, con frecuente afectación digestiva y del sistema nervioso central. En España es esporádico (incidencia 2/1.500.000 habitantes). Las manifestaciones iniciales incluyen insuficiencia renal aguda, hipertensión arterial y sintomatología neurológica (irritabilidad, somnolencia, convulsiones, ceguera cortical, hemiparesiao coma), que puede deberse a una alteración metabólica, hipertensión arterial o microangiopatía del sistema nervioso central. Además del tratamiento específico del SHU, es fundamental la valoración y seguimiento del estado neurológico para prevenir secuelas. Existen pocas referencias bibliográficas acerca de la evolución neurológica a largo plazo. Pacientes y métodos. Estudio retrospectivo de algunos factores relacionados con el pronóstico y análisis de la evolución neurológica a largo plazo de pacientes con SHU mediante una revisión de los pacientes con SHU con manifestaciones neurológicas en fase aguda tratados en nuestro centro entre 1981 y 2006. Se analizan la clínica, analítica, estudios electrofi-siológicos y neuroimagen, y su correlación con la evolución a medio y largo plazo. Resultados. De los 58 niños con SHU, 22 presentaron síntomas neurológicos en fase aguda: en siete se realizó alguna exploración complementaria neurológica; un paciente falleció, en cinco persistió algún déficit neurológico (hemiparesia, déficit cognitivo o déficit visuoperceptivo) y 16 permanecieron asintomáticos.Conclusiones. El SHU con clínica neurológica inicial asocia una alta morbilidad (un 27% de los niños con clínica neurológica), con mortalidad del 1,7%. Las convulsiones en la fase aguda no supusieron un factor de mal pronóstico en nuestro grupo. No se puede establecer una correlación entre los hallazgos de neuroimagen y la evolución a largo plazo

Introduction. Haemolytic-uraemic syndrome (HUS) is characterized by microangiopathic hemolytic anaemia,thrombopenia and multiorganic aggression, specially renal, gastrointestinal and central nervous system disturbances. Sporadic in Spain (2/1,500,000 inhabitants), its clinical onset includes acute renal failure, hypertension and central nervous systemsymptoms (irritability, drowsiness, convulsions, cortical blindness, hemiparesia or coma), due to metabolic distress, hypertension or central nervous system microangiopathy. Few long-term outcome studies have been published. Patients and methods. A retrospective analysis of a series of 58 patients with HUS between 1981 and 2006, is reported. Clinical onset, laboratory, electrophysiology, neuroimaging tests, and prognosis factors are reviewed, together with long-term clinical outcome. Results. 22 children presented neurologic symptoms, seven had some neurological test; one patient died; in five some neurological sequelae persisted (hemiparesia, cognitive deficit, visual-perception deficit), the other 16 remaining asymptomatic.Conclusions. Neurological morbility is high in HUS (27% of the children with neurological symptoms), with a 1.7% mortality. Seizure at onset was not a poor prognosis factor in our group. No positive correlation can be established between neuroimaging and long-term outcome