Extending the clinical phenotype of SPTAN1: From DEE5 to migraine, epilepsy, and subependymal heterotopias without intellectual disability.

Mutations in SPTAN1 gene, encoding the nonerythrocyte αII-spectrin, are responsible for a severe developmental and epileptic encephalopathy (DEE5) and a wide spectrum of neurodevelopmental disorders, as epilepsy with or without intellectual disability (ID) or ID with cerebellar syndrome. A certain genotype-phenotype correlation has been proposed according to the type and location of the mutation. Herein, we report three novel cases with de novo SPTAN1 mutations, one of them associated to a mild phenotype not previously described. They range from (1) severe developmental encephalopathy with ataxia and a mild cerebellar atrophy, without epilepsy; (2) moderate intellectual disability, severe language delay, ataxia and tremor; (3) normal intelligence, chronic migraine, and generalized tonic-clonic seizures. Remarkably, all these patients showed brain MRI abnormalities, being of special interest the subependymal heterotopias detected in the latter patient. Thus we extend the SPTAN1-related phenotypic spectrum, both in its radiological and clinical involvement. Furthermore, after systematic analysis of all the patients so far reported, we noted an excess of male versus female patients (20:9, p = 0.04), more pronounced among the milder phenotypes. Consequently, some protection factor might be suspected among female carriers, which if confirmed should be considered when establishing the pathogenicity of milder genetic variants in this gene.

[Familial presentation of microdeletion and inverted microduplication with array-CGH]. / Microdelecion y microduplicacion inversa de presentacion familiar con array-CGH.

INTRODUCTION. Over the years the field of genetics has advanced significantly. Following the polymerase chain reaction and mass sequencing techniques, the array-CGH technique (comparative genomic hybridization) has helped to improve genetic procedures. A resolution of up to 200 kb is currently being accomplished in the human genome. CASE REPORTS. We report the case of two sisters with delays in developmental milestones and a characteristic phenotype with normal results from initial studies of the karyotype and subtelomeric regions. Array-CGH was later used to detect a deletion and duplication that were different in each of the sisters, this being the result of a balanced paternal translocation. In the two cases, despite being the result of the same translocation, the genetic and phenotype expression were different. CONCLUSIONS. The precision achieved by means of array-CGH is making it possible to establish a correlation between minimum gains or losses of the genome and the clinical features. Chromosome 3 codes for genes that play a fundamental role in neurological development (contactins, neurotransmitter modulator proteins, etc.) and chromosome 10 codes for proteins involved in apoptosis and proteins regulating transcription. In the literature there have been reports of chromosome 3 deletion syndrome and monosomy 10. Likewise, there are also descriptions of rearrangements between these chromosomes in individuals from the same family. Nevertheless, we describe two cases of a family with a micro-deletion and an inverted microduplication, detected by means of array-CGH, that have not been reported to date. This technique can provide a diagnostic and prognostic approximation as regards development and offer genetic counselling.

TITLE: Microdelecion y microduplicacion inversa de presentacion familiar con array-CGH.Introduccion. A lo largo de los años se han logrado avances en torno a la genetica; tras la reaccion en cadena de la polimerasa y las tecnicas de secuenciacion masiva, la tecnica array-CGH (comparative genomic hybridization) ha contribuido a mejorar los procedimientos geneticos. Actualmente esta consiguiendo una resolucion de hasta 200 kb en el genoma humano. Casos clinicos. Se presentan dos hermanas con retraso en los hitos del desarrollo y fenotipo caracteristico con estudio inicial de cariotipo y de regiones subtelomericas normales. Posteriormente, mediante array-CGH se detecto en cada una una delecion y una duplicacion diferentes, fruto de una translocacion equilibrada paterna. En ambas, siendo fruto de una misma translocacion, muestra diferente expresion genetica y fenotipica. Conclusiones. La precision conseguida mediante el array-CGH esta permitiendo correlacionar minimas ganancias o perdidas del genoma con la clinica. En el cromosoma 3 se encuentran codificados genes fundamentales en el desarrollo neurologico (contactinas, proteinas moduladoras de neurotransmisores…), y en el cromosoma 10, proteinas implicadas en la apoptosis y proteinas reguladoras de la transcripcion. En la bibliografia se han descrito el sindrome de delecion del cromosoma 3 y la monosomia 10. Igualmente, hay descritos reordenamientos entre estos cromosomas en individuos de una misma familia. Sin embargo, aportamos dos casos de una familia con una microdelecion y una microduplicacion inversa, detectados mediante array-CGH, no descritos hasta el momento. Dicha tecnica puede ofrecer una aproximacion diagnostica y pronostica en cuanto a la evolucion y ofertar consejo genetico.

Microdeleción y microduplicación inversa de presentación familiar con array-CGH / Familial presentation of microdeletion and inverted microduplication with array-CGH

Introducción. A lo largo de los años se han logrado avances en torno a la genética; tras la reacción en cadena de la polimerasa y las técnicas de secuenciación masiva, la técnica array-CGH (comparative genomic hybridization) ha contribuido a mejorar los procedimientos genéticos. Actualmente está consiguiendo una resolución de hasta 200 kb en el genoma humano. Casos clínicos. Se presentan dos hermanas con retraso en los hitos del desarrollo y fenotipo característico con estudio inicial de cariotipo y de regiones subteloméricas normales. Posteriormente, mediante array-CGH se detectó en cada una una deleción y una duplicación diferentes, fruto de una translocación equilibrada paterna. En ambas, siendo fruto de una misma translocación, muestra diferente expresión genética y fenotípica. Conclusiones. La precisión conseguida mediante el array-CGH está permitiendo correlacionar mínimas ganancias o pérdidas del genoma con la clínica. En el cromosoma 3 se encuentran codificados genes fundamentales en el desarrollo neurológico (contactinas, proteínas moduladoras de neurotransmisores, etc.), y en el cromosoma 10, proteínas implicadas en la apoptosis y proteínas reguladoras de la transcripción. En la bibliografía se han descrito el síndrome de deleción del cromosoma 3 y la monosomía 10. Igualmente, hay descritos reordenamientos entre estos cromosomas en individuos de una misma familia. Sin embargo, aportamos dos casos de una familia con una microdeleción y una microduplicación inversa, detectados mediante array-CGH, no descritos hasta el momento. Dicha técnica puede ofrecer una aproximación diagnóstica y pronóstica en cuanto a la evolución y ofertar consejo genético (AU)

Introduction. Over the years the field of genetics has advanced significantly. Following the polymerase chain reaction and mass sequencing techniques, the array-CGH technique (comparative genomic hybridization) has helped to improve genetic procedures. A resolution of up to 200 kb is currently being accomplished in the human genome. Case reports. We report the case of two sisters with delays in developmental milestones and a characteristic phenotype with normal results from initial studies of the karyotype and subtelomeric regions. Array-CGH was later used to detect a deletion and duplication that were different in each of the sisters, this being the result of a balanced paternal translocation. In the two cases, despite being the result of the same translocation, the genetic and phenotype expression were different. Conclusions. The precision achieved by means of array-CGH is making it possible to establish a correlation between minimum gains or losses of the genome and the clinical features. Chromosome 3 codes for genes that play a fundamental role in neurological development (contactins, neurotransmitter modulator proteins, etc.) and chromosome 10 codes for proteins involved in apoptosis and proteins regulating transcription. In the literature there have been reports of chromosome 3 deletion syndrome and monosomy 10. Likewise, there are also descriptions of rearrangements between these chromosomes in individuals from the same family. Nevertheless, we describe two cases of a family with a microdeletion and an inverted microduplication, detected by means of array-CGH, that have not been reported to date. This technique can provide a diagnostic and prognostic approximation as regards development and offer genetic counselling (AU)

[Epidemiological surveillance of vertically-transmitted Chagas disease at three maternity hospitals in the Valencian Community]. / Vigilancia epidemiológica de la transmisión vertical de la enfermedad de Chagas en tres maternidades de la Comunidad Valenciana.

INTRODUCTION AND AIM: Immigration to Spain of Latin Americans with Chagas disease in its indeterminate phase could result in vertical transmission of the disease or transmission by transfusion or organ transplantation. To ascertain the magnitude of this problem, we investigated the prevalence of bearers among women who gave birth in 3 state maternity hospitals in the Valencian Community and the incidence of vertical transmission. PATIENTS AND METHODS: An immunoprecipitation test to detect anti-Trypanosoma cruzi antibodies was carried out on 624 pregnant Latin American women. In positive cases, indirect immunofluorescence and PCR analysis were performed on mothers. In addition, a microhematocrit and PCR analysis were performed on the newborns of these mothers, and immune precipitation was carried out from age 7 months. Chagas-positive mothers were referred for outpatient care at the hospital internal medicine departments. Percentage of positive serology was calculated for the total number of patients and by country of origin. RESULTS: A total of 29 women (4.8%; 95% CI, 3.1-6.3) were Chagas-positive; all were asymptomatic and PCR-negative. None of their children were positive to the tests performed. Bolivian women were the most frequently affected: 24 out of 137 (17.5%; 95% CI, 11.2-23.9) DISCUSSION: The high prevalence of Chagas disease in the Latin American immigrant population has raised awareness of this disease among professionals involved in the study and treatment of this illness. Further epidemiological studies are needed to establish the feasibility of universal detection programs in this population.

Vigilancia epidemiológica de la transmisión vertical de la enfermedad de Chagas en tres maternidades de la Comunidad Valenciana / Epidemiological surveillance of vertically-transmitted Chagas disease at three maternity hospitals in the Valencian Community

INTRODUCCIÓN Y OBJETIVO. La inmigración a nuestro país de poblaciones latinoamericanas afectadas de enfermedad de Chagas en fase indeterminada abre la posibilidad de transmisión vertical y por transfusión o trasplante de órganos afectados por esta enfermedad. Para averiguar la magnitud del problema, hemos investigado la prevalencia de portadoras entre las mujeres que dan a luz en tres maternidades públicas de la Comunidad Valenciana y la tasa de transmisión vertical. PACIENTES Y MÉTODOS. A un total de 624 mujeres latinoamericanas embarazadas se les practicó una prueba de inmunoprecipitación para detectar anticuerposanti-Trypanosoma cruzi. A las madres positivas se les realizó inmunofluorescencia indirecta y reacción en cadena de la polimerasa (PCR), y a sus hijos, microhematocrito yPCR en el período neonatal e inmunoprecipitación a partir de los 7 meses de vida. Se remitieron las madres seropositivas a la consulta de medicina interna. Se calculó el porcentaje de serología positiva total y por países. RESULTADOS. Un total de 29 mujeres (4,8 %; intervalo dec onfianza [IC] del 95 %: 3,1-6,3) eran seropositivas, todas asintomáticas y con PCR negativa. Ninguno de sus hijosresultó positivo en las pruebas realizadas. Las mujeres bolivianas fueron las más frecuentemente afectadas:24 de 137 (17,5 %; IC 95 %: 11,2 a 23,9).DISCUSIÓN. La elevada prevalencia de enfermedad de Chagas en la población inmigrante latinoamericana obliga a sensibilizar a los profesionales implicados en el conocimiento de esta enfermedad. Se necesitan más estudios epidemiológicos para poder establecer la conveniencia de programas de detección universal para este colectivo (AU)

INTRODUCTION AND AIM. Immigration to Spain of Latin Americans with Chagas disease in its indeterminate phase could result in vertical transmission of the disease or transmission by transfusion or organ transplantation. To ascertain the magnitude of this problem, we investigated the prevalence of bearers among women who gave birth in 3 state maternity hospitals in the Valencian Communityand the incidence of vertical transmission. PATIENTS AND METHODS. An immunoprecipitation test to detect anti-Trypanosoma cruzi antibodies was carried out on 624 pregnant Latin American women. In positive cases, indirect immunofluorescence and PCR analysis were performed on mothers. In addition, a microhematocrit and PCR analysis were performed on the new-borns of these mothers, and immune precipitation was carried out from age 7 months. Chagas-positive mothers were referred for outpatient care at the hospital internal medicine departments. Percentage of positive serology was calculated for the total number of patients and by country of origin. RESULTS. A total of 29 women (4.8 %; 95 % CI, 3.1-6.3)were Chagas-positive; all were asymptomatic and PCR-negative. None of their children were positive to the tests performed. Bolivian women were the most frequently affected: 24 out of 137 (17.5 %;95 % CI, 11.2-23.9)DISCUSSION. The high prevalence of Chagas disease in the Latin American immigrant population has raised awareness of this disease among professionals involved in the study and treatment of this illness. Further epidemiological studies are needed to establish the feasibility of universal detection programs in this population (AU)

Full breastfeeding and hospitalization as a result of infections in the first year of life.

OBJECTIVE: Our objective was to assess the effect of breastfeeding on the probability of hospitalization as a result of infectious processes during the first year of life METHODS: We followed 1385 infants from birth to age 1 year between 1996 and 1999. Recruitment and data collection were done at the 6-month well-infant visit under the National Child Health Program. Full breastfeeding, hospital admission, and other relevant variables related to the delivery, infant, mother, health services system, and sociologic aspects were recorded. The statistical analysis included Kaplan-Meier test, Cox regression to obtain the hazard ratio, and the adjusted attributable risk. RESULTS: Full breastfeeding at discharge after delivery and at 3, 4, and 6 months of age were 85%, 52%, 41%, and 15%, respectively; 78 hospital admissions as a result of infections were recorded (38 respiratory tract, 16 gastrointestinal tract). Mean age at admission was 4.1 months. After estimating the attributable risk, it was found that 30% of hospital admissions would have been avoided for each additional month of full breastfeeding. Seemingly, 100% of full breastfeeding among 4-month-old infants would avoid 56% of hospital admissions in infants who are younger than 1 year. CONCLUSIONS: On the basis of the present data, we conclude that full breastfeeding would lower the risk for hospital admission as a result of infections among infants who are younger than 1 year within an industrialized country.