Síndrome de Aicardi-Goutières: un caso familiar por alteración del gen RNASEH2B / Aicardi-Goutières syndrome: a family case due to alteration of the RNASEH2B gene

Introducción: El síndrome de Aicardi-Goutières es una encefalopatía progresiva de inicio en el primer año de vida que condiciona retraso psicomotor, microcefalia y disfunción piramidal. Tiene una prevalencia de 1-5 de cada 10.000 recién nacidos vivos. La mayoría de los casos tiene transmisión autosómica recesiva, por alteración en siete genes implicados en el metabolismo del interferón, lo cual condiciona un aumento de sus niveles en la sangre y el líquido cefalorraquídeo, y afecta al cerebro (leucodistrofia, atrofia corticosubcortical, calcificaciones en los núcleos basales…), la piel y el sistema inmunitario. Caso clínico: Se trata de dos hermanos que presentan la variante p.Ala177Thr en homocigosis en el gen RNASEH2B; ambos progenitores, consanguíneos, son portadores. El primer hermano comenzó a los 10 meses con hipotonía axial, hipertonía de las extremidades, regresión psicomotriz y movimientos distónicos. El segundo hermano presentó desde el nacimiento tono axial bajo con hipertonía de las extremidades, a los 4 meses se hallaron calcificaciones en los núcleos lenticuloestriados mediante ecografía transfontalar y a los 6 meses inició movimientos distónicos y nistagmo intermitente. Ambos han desarrollado tetraparesia espástica y permanecen estables con 8 y 10 años, pese a las complicaciones propias del síndrome. Conclusiones: El síndrome de Aicardi-Goutières es una entidad rara que debe tenerse presente ante situaciones que cursen con alteración del desarrollo psicomotor y calcificaciones intracraneales; destacamos la importancia del diagnóstico genético tanto para conocer el pronóstico de nuestros pacientes en función de su alteración genética como para ofrecer consejo genético a sus familias.(AU)

Introduction: Aicardi-Goutières syndrome is a progressive encephalopathy with onset in the first year of life that conditions psychomotor retardation, microcephaly and pyramidal dysfunction. It has a prevalence of 1-5 in 10,000 newly live births. Most cases have autosomal recessive transmission, due to alteration in seven genes involved in the metabolism of interferon, which causes an increase in its levels in the blood and cerebrospinal fluid, and affects the brain (leukodystrophy, corticosubcortical atrophy, calcifications in the basal ganglia…), the skin and the immune system. Clinical case: They are two brothers who present the homozygous p.Ala177Thr variant in the RNASEH2B gene; both of them parents, consanguineous, are carriers. The first sibling started at 10 months with axial hypotonia, hypertonia of the extremities, psychomotor regression and dystonic movements. The second brother presented from the birth low axial tone with hypertonia of the extremities, at 4 months calcifications were found in the nuclei lenticulostriated by transfontalar ultrasound and, at 6 months, she started dystonic movements and intermittent nystagmus. Both have developed spastic tetraparesis and remain stable at 8 and 10 years, despite complications typical of the syndrome. Conclusions: The Aicardi-Goutières syndrome is a rare entity that should be taken into account in situations that occur with altered psychomotor development and intracranial calcifications; we highlight the importance of diagnosis both to know the prognosis of our patients based on their genetic alteration and to offer genetic counseling to their families.(AU)

[Aicardi-Goutieres syndrome: a family case due to alteration of the RNASEH2B gene]. / Síndrome de Aicardi-Goutières: un caso familiar por alteración del gen RNASEH2B.

INTRODUCTION: Aicardi-Goutieres syndrome is a progressive encephalopathy with onset in the first year of life that conditions psychomotor retardation, microcephaly and pyramidal dysfunction. It has a prevalence of 1-5 in 10,000 newly live births. Most cases have autosomal recessive transmission, due to alteration in seven genes involved in the metabolism of interferon, which causes an increase in its levels in the blood and cerebrospinal fluid, and affects the brain (leukodystrophy, corticosubcortical atrophy, calcifications in the basal ganglia…), the skin and the immune system. CLINICAL CASE: They are two brothers who present the homozygous p.Ala177Thr variant in the RNASEH2B gene; both of them parents, consanguineous, are carriers. The first sibling started at 10 months with axial hypotonia, hypertonia of the extremities, psychomotor regression and dystonic movements. The second brother presented from the birth low axial tone with hypertonia of the extremities, at 4 months calcifications were found in the nuclei lenticulostriated by transfontalar ultrasound and, at 6 months, she started dystonic movements and intermittent nystagmus. Both have developed spastic tetraparesis and remain stable at 8 and 10 years, despite complications typical of the syndrome. CONCLUSIONS: The Aicardi-Goutieres syndrome is a rare entity that should be taken into account in situations that occur with altered psychomotor development and intracranial calcifications; we highlight the importance of diagnosis both to know the prognosis of our patients based on their genetic alteration and to offer genetic counseling to their families.

TITLE: Síndrome de Aicardi-Goutières: un caso familiar por alteración del gen RNASEH2B.Introducción. El síndrome de Aicardi-Goutières es una encefalopatía progresiva de inicio en el primer año de vida que condiciona retraso psicomotor, microcefalia y disfunción piramidal. Tiene una prevalencia de 1-5 de cada 10.000 recién nacidos vivos. La mayoría de los casos tiene transmisión autosómica recesiva, por alteración en siete genes implicados en el metabolismo del interferón, lo cual condiciona un aumento de sus niveles en la sangre y el líquido cefalorraquídeo, y afecta al cerebro (leucodistrofia, atrofia corticosubcortical, calcificaciones en los núcleos basales…), la piel y el sistema inmunitario. Caso clínico. Se trata de dos hermanos que presentan la variante p.Ala177Thr en homocigosis en el gen RNASEH2B; ambos progenitores, consanguíneos, son portadores. El primer hermano comenzó a los 10 meses con hipotonía axial, hipertonía de las extremidades, regresión psicomotriz y movimientos distónicos. El segundo hermano presentó desde el nacimiento tono axial bajo con hipertonía de las extremidades, a los 4 meses se hallaron calcificaciones en los núcleos lenticuloestriados mediante ecografía transfontalar y a los 6 meses inició movimientos distónicos y nistagmo intermitente. Ambos han desarrollado tetraparesia espástica y permanecen estables con 8 y 10 años, pese a las complicaciones propias del síndrome. Conclusiones. El síndrome de Aicardi-Goutières es una entidad rara que debe tenerse presente ante situaciones que cursen con alteración del desarrollo psicomotor y calcificaciones intracraneales; destacamos la importancia del diagnóstico genético tanto para conocer el pronóstico de nuestros pacientes en función de su alteración genética como para ofrecer consejo genético a sus familias.

[Children with ADHD: a retrospective description of their behavioural features as toddlers]. / Estilo comportamental al inicio del segundo año de vida: estudio retrospectivo en escolares afectados de trastorno por déficit de atención e hiperactividad.

OBJECTIVES: To study the relationship between behavioural profile of children suffering from Attention Deficit Hyperactivity Disorder (ADHD) and the previous behavioural style of these patients as toddlers. SUBJECTS AND METHODS: We asked the parents of 50 schoolchildren with ADHD, and those of 30 controls, to fill in a Spanish version of the Toddler Behaviour Questionnaire (TBQ) from their retrospective perception of their children's behaviour as toddlers. TBQ items were grouped by factor analysis; t-Student between the scores of both groups and a multiple correlation analysis of TBQ and DSM-IV-ADHD-RS in each of the groups were used. RESULTS: Children in the ADHD group were reported by parents to have had a different toddler behavioural profile in comparison to that of control children (P<0.05). These differences were associated with adapting to new environments, mood, regularity and stability of play behaviour. A correlation was found between behavioural profile in DSM-IV-ADHD- RS and TBQ. CONCLUSIONS: The results of this study should be interpreted with caution. However, they suggest that in the fifth trimester of life a particular behavioural style as regards regularity, stability of play, and mood, could indicate a risk of developing ADHD in the future. This behavioural style should be taken into consideration in rearing and early education prospective studies.

[Interactive formats and executive functions in early development]. / Formatos interactivos y funciones ejecutivas en el desarrollo temprano.

INTRODUCTION: Cognitive control improve planning, action selection to get a goal (flexibly) and their modifiability. Executive functions are a functional construct related with solving process and goal maintenance. AIM: Among executive functions we will study the resistance of interference, stopping irrelevant information and the inhibition of a dominant but inapropiate scheme as well as the influence of the type of tutoring during action execution. SUBJECTS AND METHODS: We studied 15 infants with alternative courses of development (typical babies and Down' syndrome babies) at a developmental level equivalent to 15 months old, and 6 months later. Infant' spontaneous activity is videotaped longitudinally for a 15 minutes period, activity units are codified by a mixed system of categories and quantified in order to know the significative differences on tutoring types, their dynamic an effects associated with infant's executive functions. RESULTS: a) Adult's directive tutoring is more frequent with Down's syndrome babies than with typical babies; b) Directive tutoring is less adjusted and produces more interferences; c) There is a differential capacity to interference resistance, less present in the Down's syndrome babies; d) Executive functioning shows developmental and differential trends. CONCLUSIONS: If development is individual and socially influenced, the individual differential efficacy of executive functions and the type of tutoring contributes to typical or atypical developmental course. Educational and health consequences are proposed.

[Evaluation and diagnosis of patients with developmental delay: standardised protocols from the paediatric point of view]. / Evaluación y diagnóstico del paciente con retraso del desarrollo: protocolos estandarizados desde el punto de vista del neuropediatra.

INTRODUCTION AND AIMS: The identification of the causes of mental retardation (MR) is of great importance because of the consequences it has in the intervention, prognosis, knowledge of risk of recurrence and its prevention. The purpose of this review is to provide a global evaluation of the child with developmental delay or with MR in day-to-day clinical praxis of the neuropaediatrician who has to put aetiological diagnosis in practice. DEVELOPMENT: To this end we conduct a review of the evidence-based guidelines published by the leading groups of experts that assess the weight of diagnostic tests in the initial evaluation of children with MR and propose an algorithm that helps the clinician to make decisions. CONCLUSIONS: A good patient record including the familial and personal history, the examination and observation of behaviour is essential before starting the laboratory and imaging tests in a rational manner. At the outset, cytogenetic and molecular genetic studies are indicated to study fragile X syndrome and neuroimaging, preferably magnetic resonance, should be employed above all when anomalies are observed in the examination. Ophthalmologic and auditory evaluation is recommended in all cases. Routine metabolic screening is not indicated at the outset; studies to investigate thyroid (T4 and TSH) and other metabolic pathologies can be considered when the child has not been subject to neonatal metabolic screening or when there is clinical evidence of it. Routine electroencephalogram studies are not recommended, but can be considered if suggested by the clinical history. Likewise, the clinician may consider a study for toxins, if the clinical history suggests it, and a genetic study of Rett syndrome, in the case of girls with MR that cannot be accounted for by other causes.

[Evolution of the infant mortality rate in la Rioja in Spain (1980-1998)]. / Evolución de la mortalidad infantil de La Rioja (1980-1998).

BACKGROUND: Before the 1990s, the infant mortality rate in the province of La Rioja was the highest in Spain and was 60 % higher than the Spanish average. This led to the implementation of several measures to lower this rate. OBJECTIVES: To analyze infantile mortality rates and their components in La Rioja before and after the implementation of the measures and to compare these rates with those of the other autonomous communities and with the national average. METHODS: The study period was from 1980 to 1998. Data were obtained from the National Statistics Institute, the official mortality register of La Rioja and the records of the San Millán-San Pedro Hospital in Logroño (La Rioja). The World Health Organization's definition of mortality was used. RESULTS: From 1980-1998 the infant mortality rate in La Rioja decreased from 15.4 to 5.9 per thousand (neonatal mortality: from 10.84 to 3.68; postneonatal mortality: from 4.56 to 2.21; perinatal mortality: from 20.54 to 5.1). In the same period, the national rate decreased from 12.34 to 4.85. Data from the autonomous communities were analyzed by comparing the last two 5-year periods: La Rioja showed a decrease of 40.41 % (from 10.71 to 6.06 per thousand), which was the greatest decrease in Spain. CONCLUSIONS: The decrease in the infant mortality rate in La Rioja during the last decade indicates that the measures adopted have been successful. Even so, these rates remain among the highest in Spain and continued efforts should be made to reduce them.