Molecular characterization of congenital myasthenic syndromes in Spain.

Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic disorders, all of which impair neuromuscular transmission. Epidemiological data and frequencies of gene mutations are scarce in the literature. Here we describe the molecular genetic and clinical findings of sixty-four genetically confirmed CMS patients from Spain. Thirty-six mutations in the CHRNE, RAPSN, COLQ, GFPT1, DOK7, CHRNG, GMPPB, CHAT, CHRNA1, and CHRNB1 genes were identified in our patients, with five of them not reported so far. These data provide an overview on the relative frequencies of the different CMS subtypes in a large Spanish population. CHRNE mutations are the most common cause of CMS in Spain, accounting for 27% of the total. The second most common are RAPSN mutations. We found a higher rate of GFPT1 mutations in comparison with other populations. Remarkably, several founder mutations made a large contribution to CMS in Spain: RAPSN c.264C > A (p.Asn88Lys), CHRNE c.130insG (Glu44Glyfs*3), CHRNE c.1353insG (p.Asn542Gluf*4), DOK7 c.1124_1127dup (p.Ala378Serfs*30), and particularly frequent in Spain in comparison with other populations, COLQ c.1289A > C (p.Tyr430Ser). Furthermore, we describe phenotypes and distinguishing clinical signs associated with the various CMS genes which might help to identify specific CMS subtypes to guide diagnosis and management.

[Aicardi-Goutieres syndrome due to mutation of the IFIH1 gene with pontine involvement. A case report]. / Sindrome de Aicardi-Goutieres por mutacion en el gen IFIH1 con afectacion pontina. A proposito de un caso.

INTRODUCTION: Aicardi-Goutieres syndrome is a rare progressive subacute encephalopathy of early onset - generally in the first year of life - characterised by psychomotor retardation, microcephaly, alterations in the white matter of the brain, intracranial calcifications, pleocytosis and elevated levels of interferon alpha in the cerebrospinal fluid. It is associated to an increase in the expression of genes stimulated by interferon in peripheral blood, a fact known as the interferon signature. The levels of genes stimulated by interferon has been postulated as a good biomarker, as they remain high in peripheral blood over time and are more sensitive, in comparison to determinations of interferon alpha and neopterins in cerebrospinal fluid, which descend as of one year of life. To date, mutations have been reported in seven genes that overstimulate the interferon alpha pathway, and the last to be discovered is IFIH1 (interferon induced with helicase C domain 1), with a pattern of dominant autosomal inheritance. CASE REPORT: We present the first case reported in the Hispanic literature caused by a de novo mutation in the IFIH1 gene. The clinical features, studies conducted and review of the clinical, neuroradiological and genetic aspects are described. CONCLUSIONS: The inheritance of the mutations reported for Aicardi-Goutieres syndrome was classically considered as being recessive autosomal, but these findings show that dominant autosomal mutations in the IFIH1 gene can cause the disease. As a previously unreported neuroimaging finding, it presents a lesion consisting in cystic encephalomalacia in the pons.

TITLE: Sindrome de Aicardi-Goutieres por mutacion en el gen IFIH1 con afectacion pontina. A proposito de un caso.Introduccion. El sindrome de Aicardi-Goutieres es una rara encefalopatia subaguda progresiva de inicio precoz ­generalmente en el primer año de vida­ caracterizada por retraso psicomotor, microcefalia, alteraciones en la sustancia blanca cerebral, calcificaciones intracraneales, pleocitosis y niveles elevados de interferon alfa en el liquido cefalorraquideo. Asocia un incremento en la expresion de los genes estimulados por interferon en la sangre periferica, hecho conocido como interferon signature. Los niveles de genes estimulados por interferon se han postulado como un buen biomarcador, pues se mantienen elevados en la sangre periferica en el tiempo y son mas sensibles, en comparacion con las determinaciones de interferon alfa y neopterinas en el liquido cefalorraquideo, las cuales descienden a partir del año de vida. Hasta la fecha se han descrito mutaciones en siete genes que sobreestimulan la via del interferon alfa, y el ultimo en descubrirse ha sido el IFIH1 (interferon induced with helicase C domain 1), con un patron de herencia autosomico dominante. Caso clinico. Se presenta el primer caso descrito en la bibliografia hispana debido a mutacion de novo en el gen IFIH1. Se expone el cuadro clinico, los estudios realizados y la revision de los aspectos clinicos, neurorradiologicos y geneticos. Conclusiones. La herencia de las mutaciones descritas para el sindrome de Aicardi-Goutieres era clasicamente autosomica recesiva, pero estos hallazgos muestran que mutaciones autosomicas dominantes en el gen IFIH1 pueden causar la enfermedad. Como hallazgo de neuroimagen no descrito previamente, presenta una lesion de encefalomalacia quistica en la protuberancia.

Migraña hemipléjica familiar tipo II: a propósito de dos casos pediátricos / Familial hemiplegic migraine type 2: two paediatric case reports

Introducción. La migraña hemipléjica familiar es un subtipo poco común de migraña con aura que incluye, en su transcurso, un defecto motor junto con síntomas visuales, sensoriales o con trastornos del habla. Puede asociar síntomas de migraña basilar, coma y convulsiones. La migraña hemipléjica familiar tipo II supone el 25% de ellas. Casos clínicos. Se presentan dos pacientes que comienzan desde los 4 años de edad con episodios deficitarios motores ocrisis convulsivas, junto con una importante alteración del sensorio, de horas de duración, a veces desencadenados por traumatismos banales. Se detallan las características clínicas, evolutivas y los estudios realizados. El estudio genético revela mutaciones en el gen ATP1A2: en un caso una sustitución nucleotídica en el exón 18 (G2501A) previamente descrita; en el otro caso, un cambio inédito (c.381+3 G>T) en el intrón 4. Conclusión. Recomendamos sospechar esta entidad cuando se detecte una discordancia entre la duración o gravedad de la convulsión y la duración y las características del estupor posterior (AU)

Introduction. Familial hemiplegic migraine is a rare subtype of migraine with aura that includes, as it progresses, a motor defect together with visual or sensory symptoms or speech disorders. It may be associated to symptoms such as basilar migraine, coma and convulsions. Familial hemiplegic migraine type 2 accounts for 25% of them. Case reports. Two patients, who started at the age of 4 years with episodes of motor deficits or seizures, together with animportant sensory disorder that lasted for hours, which were sometimes triggered by banal traumatic injuries. A detaileddescription of the clinical and developmental features, as well as the studies conducted, is provided. The genetic study revealed mutations in gene ATP1A2: in one case this consisted in a nucleotide substitution in exon 18 (G2501A) that had already been reported, while in the other case there was a previously unknown change (c.381+3 G>T) in intron 4. Conclusions. We recommend that this condition should be suspected when a disagreement between the duration or the severity of the seizures and the duration and characteristics of the ensuing stupor is detected (AU)

Glioma tectal, autismo y uso del chiste / Tectal glioma, autism and the use of jokes

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