The solitary median maxillary central incisor (SMMCI) syndrome: Associations, prenatal diagnosis, and outcomes.

Solitary median maxillary central incisor (SMMCI) syndrome is a complex disorder consisting of multiple, developmental defects involving midline structures of the head, which includes the cranial bones, the maxilla, and its container dentition (specifically the central incisor tooth germ), together with other midline structures of the body. SMMCI may appear as an isolated trait or in association with other midline developmental anomalies. We describe the case of a patient with SMMCI. He presented with a solitary median maxillary incisor, short stature, corpus callosum anomalies and a microform of holoprosencephaly (HPE), diabetes insipidus, and neurodevelopmental delay. The diagnosis was performed postnatally based on clinical features, radiological imaging, and a comprehensive genetic study. SMMCI can be diagnosed during the prenatal or neonatal periods or during infancy. Evaluation of the superior maxillary bone is important for prenatal diagnosis. Direct evaluation through bidimensional ultrasound or the use of multiplanar ultrasound or tridimensional reconstruction should be performed in cases of brain or face malformations. Early diagnosis can contribute to improved prenatal assessment and postnatal management.

Neurofibromatosis type I: mutation spectrum of NF1 in spanish patients.

Neurofibromatosis type I (NF1) is one of the most common genetic disorders in humans. NF1, a tumor predisposition syndrome, is caused by heterozygous pathogenic variants in the NF1 gene. Molecular genetic testing of NF1 is complex, especially because of the presence of a high number of partial pseudogenes, some of them with a high percentage of sequence identity. In this study, we have analyzed the largest cohort of NF1 Spanish patients (150 unrelated individuals suspected of having NF1 and 53 relatives, making a total of 203 individuals). Mutation analysis of the entire coding region was performed in all unrelated index patients. Additionally, the Multiplex Ligation-dependent Probe Amplification (MLPA) test of the NF1 gene and SPRED1 gene analysis (sequencing and MLPA test) was performed in some of the negative patients for NF1 point mutations. When fulfilling the National Institutes of Health (NIH) criterion for the clinical diagnosis of NF1, the detection rate was 79%. Among the 80 genetically confirmed NF1 probands, we detected 69 different pathogenic variants. Two mutations (3%) were gross deletions of the whole gene, the remaining 78 mutations (97%) were small changes spread among all NF1 exons. Among these 69 different mutations detected, 42 mutations were described elsewhere, and 27 mutations were novel mutations. When segregation was studied, 67% of mutations resulted de novo variants. No genetic mosaicism was detected on patients' parents.

Neuropatía óptica de Leber: utilidad de la secuenciación masiva en el estudio de mutaciones mitocondriales en aparente homoplasmia / Leber hereditary optic neuropathy: Usefulness of next generation sequencing to study mitochondrial mutations on apparent homoplasmy

Fundamento y objetivo: La neuropatía óptica hereditaria de Leber se caracteriza por una pérdida de visión aguda o subaguda, producida por mutaciones en el ADN mitocondrial. Pacientes y métodos: Presentamos el estudio molecular realizado en una familia en la que solo uno de sus miembros presentaba signos de la enfermedad. Resultados: En el caso índice y en la madre se detectó la mutación m.11778G>A en el gen MT-ND4 en heteroplasmia. La hermana del caso índice, sin manifestaciones oculares, acudió a consulta para consejo genético. El estudio de dicha mutación por secuenciación Sanger mostró que la portaba en homoplasmia. Sin embargo, mediante secuenciación de última generación (NGS) se pudo comprobar que se encontraba realmente en heteroplasmia. Conclusiones: Confirmar que una mutación se encuentra en homoplasmia es importante cara al consejo genético. Hemos observado que la NGS permite distinguir entre grados elevados de heteroplasmia y verdaderas homoplasmias y, por tanto, es de utilidad en el estudio de pacientes en los que se detectan mutaciones en homoplasmia con metodologías de menor sensibilidad analítica (AU)

Background and objective: Leber hereditary optic neuropathy is characterized by acute and subacute visual loss, produced by mitochondrial DNA mutations. Patients and methods: The molecular study of a family with only one affected member is presented. Results: In the index case and in her mother, the mitochondrial mutation m.11778G>A in the MT-ND4 was detected in the heteroplasmic state. The index case's sister, without ocular manifestations, asked for genetic counseling. The study of the mentioned mutation by Sanger sequencing identified it in an apparent homoplasmic state. However, by means of next-generation sequencing (NGS), the mutation was actually in a heteroplasmic state. Conclusions: Regarding genetic counseling, verifying a mutation in homoplasmic state is really important. We have observed that NGS allows us to discriminate between high levels of heteroplasmy and homoplasmy, meaning that it is a useful technique for the analysis of apparent homoplasmic results obtained with less sensitive technique, as Sanger sequencing (AU)

[Leber hereditary optic neuropathy: Usefulness of next generation sequencing to study mitochondrial mutations on apparent homoplasmy]. / Neuropatía óptica de Leber: utilidad de la secuenciación masiva en el estudio de mutaciones mitocondriales en aparente homoplasmia.

BACKGROUND AND OBJECTIVE: Leber hereditary optic neuropathy is characterized by acute and subacute visual loss, produced by mitochondrial DNA mutations. PATIENTS AND METHODS: The molecular study of a family with only one affected member is presented. RESULTS: In the index case and in her mother, the mitochondrial mutation m.11778G>A in the MT-ND4 was detected in the heteroplasmic state. The index case's sister, without ocular manifestations, asked for genetic counseling. The study of the mentioned mutation by Sanger sequencing identified it in an apparent homoplasmic state. However, by means of next-generation sequencing (NGS), the mutation was actually in a heteroplasmic state. CONCLUSIONS: Regarding genetic counseling, verifying a mutation in homoplasmic state is really important. We have observed that NGS allows us to discriminate between high levels of heteroplasmy and homoplasmy, meaning that it is a useful technique for the analysis of apparent homoplasmic results obtained with less sensitive technique, as Sanger sequencing.

[Influenza virus in pediatrics. A reason for hospitalization]. / El virus de la gripe en pediatría. Un motivo de hospitalización.

INTRODUCTION: Influenza infection in infants and children has been classically underestimated due to its non-specific symptoms, which sometimes overlap those of other respiratory viruses. Infants under 24 months are a risk group and school-aged children are a major source of influenza infection. The aim of this study was to describe the clinical and epidemiological characteristics of children hospitalized for flu, including co-infections and the differences as compared to other respiratory viruses. The effectiveness of a test for rapid diagnosis of this condition was assessed. MATERIAL AND METHODS: Prospective, descriptive study in children < 5 years of age hospitalized from 1 December 2003 to 28 February 2004 with respiratory processes or fever of unknown origin. Polymerase chain reaction (PCR) testing for influenza A (IA) and B, respiratory syncytial virus A (RSV-A) and B, and parainfluenza 1, 2 and 3 was performed in nasopharyngeal aspirate, as well as a test for rapid diagnosis of influenza. RESULTS: A total of 203 samples were included. PCR was positive for influenza in 11.3% (23/203); IA in 21 cases (20 H3N2, 1 H1N1). Co-infections were frequent (10/23), mainly IA with RSV-A. The rapid diagnostic test had a sensitivity of 45.5%. Median age of patients with flu was 4.87 months (5 days-3.5 years); 69.5% were < 24 months. Gastrointestinal symptoms were associated with fever and respiratory symptoms more often than in other viral infections (P < 0.05). Only 2.9% of patients with a recommendation for flu vaccination had received the vaccination. CONCLUSIONS: Flu is a major cause of hospitalization in infants and children, particularly those aged < 24 months. Early diagnosis of this condition may avoid unnecessary use of additional tests and antibiotics. Vaccination coverage is low; vaccination between 6 and 24 months seems advisable.

El virus de la gripe en pediatría. Un motivo de hospitalización / Influenza virus in pediatrics. A reason for hospitalization

Introducción. La gripe en pediatría ha sido clásicamente infradiagnosticada, por su clínica inespecífica y solapable con otros virus respiratorios. Los menores de 24 meses constituyen un grupo de riesgo y los escolares son una fuente importante de contagio. El objetivo de este estudio es describir la clínica y epidemiología de niños ingresados por gripe, estudiando coinfecciones y comparando con otros virus respiratorios. Se valoró la efectividad de un test de diagnóstico rápido. Material y métodos. Estudio descriptivo prospectivo en menores de 5 años hospitalizados entre el 1 de diciembre de 2003 y el 28 de febrero de 2004 por cuadro respiratorio o fiebre sin foco aparente. Se realizó reacción en cadena de polimerasa (PCR) a virus de la gripe A (IA) y B, virus respiratorio sincitial A (VRS-A) y B y parainfluenza 1, 2 y 3 en aspirado nasofaríngeo y test de diagnóstico rápido de gripe. Resultados. Se incluyeron 203 muestras, siendo la PCR positiva a virus de la gripe en un 11,3% (23/203): IA 21 casos (20 H3N2, 1 H1N1). Las coinfecciones fueron frecuentes (10/23), destacando la asociación IA y VRS-A. El test de diagnóstico rápido tuvo una sensibilidad del 45,5%. La mediana de edad de los pacientes con gripe fue 4,87 meses (5 días-3,5 años); un 69,5% eran menores 24 meses. A la fiebre y síntomas respiratorios, asociaron síntomas gastrointestinales con más frecuencia que los otros virus (p < 0,05). Sólo un 2,9% de los pacientes con indicación de vacunación antigripal la había recibido. Conclusiones. La gripe es causa importante de hospitalización en pediatría, especialmente en menores 24 meses. Su diagnóstico precoz evitaría el uso innecesario de pruebas complementarias y antibióticos. Existe una baja cobertura vacunal. Sería interesante la vacunación entre los 6 y los 24 meses (AU)

Introduction. Influenza infection in infants and children has been classically underestimated due to its non-specific symptoms, which sometimes overlap those of other respiratory viruses. Infants under 24 months are a risk group and school-aged children are a major source of influenza infection. The aim of this study was to describe the clinical and epidemiological characteristics of children hospitalized for flu, including co-infections and the differences as compared to other respiratory viruses. The effectiveness of a test for rapid diagnosis of this condition was assessed. Material and methods. Prospective, descriptive study in children < 5 years of age hospitalized from 1 December 2003 to 28 February 2004 with respiratory processes or fever of unknown origin. Polymerase chain reaction (PCR) testing for influenza A (IA) and B, respiratory syncytial virus A (RSV-A) and B, and parainfluenza 1, 2 and 3 was performed in nasopharyngeal aspirate, as well as a test for rapid diagnosis of influenza. Results. A total of 203 samples were included. PCR was positive for influenza in 11.3% (23/203); IA in 21 cases (20 H3N2, 1 H1N1). Co-infections were frequent (10/23), mainly IA with RSV-A. The rapid diagnostic test had a sensitivity of 45.5%. Median age of patients with flu was 4.87 months (5 days-3.5 years); 69.5% were < 24 months. Gastrointestinal symptoms were associated with fever and respiratory symptoms more often than in other viral infections (P < 0.05). Only 2.9% of patients with a recommendation for flu vaccination had received the vaccination. Conclusions. Flu is a major cause of hospitalization in infants and children, particularly those aged < 24 months. Early diagnosis of this condition may avoid unnecessary use of additional tests and antibiotics. Vaccination coverage is low; vaccination between 6 and 24 months seems advisable (AU)

High prevalence of hepatitis C virus subtypes 4c and 4d in Malaga (Spain): phylogenetic and epidemiological analyses.

Hepatitis C virus (HCV) is a major aetiological agent of chronic hepatitis and it may lead to the development of liver cirrhosis and hepatocellular carcinoma. HCV has been classified into six clades as a result of high genetic variability. A commercial procedure to genotype HCV in 678 patients from Carlos Haya Regional University Hospital, Malaga was used to study the distribution of HCV genotypes in Malaga, southern Spain. A high prevalence of HCV-4 (10.2%) was found. This genotype is found more commonly in Egypt, Central Africa and the Middle East. The distribution of the different subtypes in the 69 patients with HCV-4 was as follows: 4.3% subtype 4e, 7.2% subtype 4a, 11.5% not subtypable, and 76.8% subtype 4c/4d. Of the 53 4c/4d patients, 69% were intravenous drug users and 31% non-intravenous drug users. In order to characterise further the HCV-4c/4d patients, sequences of the non-structural 5B gene (393 bp) were obtained from 36 HCV-4c/4d-infected untreated patients. Phylogenetic tree topologies distinguished clearly the two subtypes: 11 patients were infected by subtype 4c and 25 by 4d. This phylogenetic analysis, reinforced by the epidemiological characteristics, suggests the extension of the HCV-4c and -4d subtypes in the area of Malaga among both intravenous drug users and non-intravenous drug users.