A novel mutation in the NNT gene causing familial glucocorticoid deficiency, with a literature review.

Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder characterized by low cortisol levels despite elevated adrenocorticotropin (ACTH). Mineralocorticoid secretion is classically normal. Clinical manifestations are secondary to low cortisol levels (recurrent hypoglycemia, chronic asthenia, failure to thrive, seizures) and high levels of ACTH (cutaneous-mucosal hyperpigmentation). FGD is often caused by mutations in the ACTH melanocortin 2 receptor gene (MC2R, 18p11.21, FGD type 1) or melanocortin receptor 2 accessory protein gene (MRAP, 21q22.11, FGD type 2). But mutations have also been described in other genes: the steroidogenic acute regulatory protein (STAR, 8q11.2q13.2, FGD type 3), nicotinamide nucleotide transhydrogenase (NNT, 5p12, FGD type 4) and thioredoxin reductase 2 genes (TXNRD2, 22q11.21, FGD type 5). We report the case of a 3-year-old boy recently diagnosed with FGD type 4 due to a novel mutation in NNT gene. A homozygous variant in exon 18 of the NNT gene, NM_012343.3:c.2764C>T, p.(Arg922*), determines a stop codon and, consequently, a non-functional truncated protein or absence of protein due to the nonsense-mediated decay (NMD) mechanism. We review the recent literature on NNT mutations and clinical presentations, which are broader than suspected. This disorder can result in significant morbidity and is potentially fatal if untreated. Precise diagnosis allows correct treatment and follow-up.

Characteristics and outcomes of the Spanish registry for pediatric patients with bicuspid aortic valve (REVAB).

INTRODUCTION AND OBJECTIVES: Bicuspid aortic valve (BAV) disorder is the most common congenital heart disease. The aim of this study was to describe the characteristics of 0- to 18-year olds with BAV in a population-based registry. METHODS: Data from all pediatric patients were obtained from the Spanish registry for pediatric patients with bicuspid aortic valve (REVAB) (< 18 years). For data analysis, patients with BAV were divided into 2 groups by their features: isolated BAV and BAV with associated congenital heart disease. RESULTS: We included 1681 patients from 33 hospitals. Males accounted for 69.6% (n = 1158). Valve morphology was horizontal in 63.4% (n = 1012) and pure (Sievers type 0) in 28.4% (n=469). Isolated BAV was present in 63.7% (n=1060), and concomitant left-sided obstructive lesions in 23.4% (n=390). Interventions were required in 8.6% (n=145). CONCLUSION: These data represent the first large, population-based description of the clinical presentations and outcomes of patients enrolled in the Spanish registry for pediatric patients with bicuspid aortic valve.

Variables ambientales y genéticas relacionadas con alteraciones en la adquisición del lenguaje en la infancia / Environmental and genetic variables related with alterations in language acquisition in early childhood

Introducción. Los problemas en la correcta adquisición del lenguaje se han estudiado mucho, pero con escasas conclusiones globales; a ello contribuye la variabilidad individual, la existencia de diferentes medidas para evaluar el lenguaje y a que en su desarrollo participa una compleja red de factores genéticos y ambientales. Objetivo. Revisar las variables ambientales y genéticas que se han investigado hasta la actualidad, para comprender mejor las causas de los trastornos específicos del lenguaje y crear nuevas evidencias que faciliten la elaboración de sistemas de detección precoz de estos trastornos. Desarrollo. Dentro de las variables ambientales relacionadas con peor desarrollo en el lenguaje infantil están el sexo masculino, un nivel educacional maternal bajo, una historia familiar de problemas en el lenguaje o problemas psiquiátricos, los problemas perinatales y los problemas de salud en la infancia. El bilingüismo parece ser un factor protector. El temperamento y el lenguaje tienen relación. Dentro de los factores genéticos existen ya varios genes específicos asociados con el lenguaje, dos de ellos con una influencia mayor en su adquisición fisiológica: FOXP2 y CNTNAP2. Los otros genes más relacionados con trastornos específicos del lenguaje son ATP2C2, CMIP, ROBO2, ZNF277 y NOP9. Conclusiones. La clave para entender el desarrollo de los trastornos específicos del lenguaje radica en llegar a comprender el verdadero papel que desempeñan los genes en la ontogenia, regulando los diferentes procesos de desarrollo y cómo este papel se ve modulado por el ambiente (AU)

Introduction. A great deal of research has addressed problems in the correct acquisition of language, but with few overall conclusions. The reasons for this lie in the individual variability, the existence of different measures for assessing language and the fact that a complex network of genetic and environmental factors are involved in its development. Aim. To review the environmental and genetic variables that have been studied to date, in order to gain a better understanding of the causes of specific language impairment and create new evidence that can help in the development of screening systems for the early detection of these disorders. Development. The environmental variables related with poorer early child language development include male gender, low level of education of the mother, familial history of problems with language or psychiatric problems, perinatal problems and health problems in early childhood. Bilingualism seems to be a protective factor. Temperament and language are related. Within the genetic factors there are several specific genes associated with language, two of which have a greater influence on its physiological acquisition: FOXP2 and CNTNAP2. The other genes that are most related with specific language disorders are ATP2C2, CMIP, ROBO2, ZNF277 and NOP9. Conclusions. The key to comprehending the development of specific language disorders lies in reaching an understanding of the true role played by genes in the ontogenesis, in the regulation of the different developmental processes, and how this role is modulated by the environment (AU)

Miocardiopatía hipertrófica intraútero y síndrome de Noonan neonatal: una asociación a recordar / Prenatal hypertrophic cardiomyopathy and neonatal noonan syndrome: an association to remember

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