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Contains fulltext : 182761.pdf (Publisher’s version ) (Open Access) Burn-McKeown syndrome (BMKS) is a rare syndrome characterized by choanal atresia, prominent ears, abnormalities of the outer third of the lower eyelid, structural cardiac abnormalities, conductive and sensorineural hearing loss, and cleft lip. Recently, causative compound heterozygous variants were identified in TXNL4A. We analyzed an individual with clinical features of BMKS and her parents by whole-genome sequencing and identified compound heterozygous variants in TXNL4A (a novel splice site variant (c.258-2A>G, (p.?)) and a 34 bp promoter deletion (hg19 chr18:g.77748581_77748614del (type 1Delta) in the proband). Subsequently, we tested a cohort of 19 individuals with (mild) features of BMKS and 17 individuals with isolated choanal atresia for causative variants in TXNL4A by dideoxy-sequence analysis. In one individual with BMKS unrelated to the first family, we identified the identical compound heterozygous variants. In an individual with isolated choanal atresia, we found homozygosity for the same type 1Delta promoter deletion, whilst in two cousins from a family with choanal atresia and other minor anomalies we found homozygosity for a different deletion within the promoter (hg19 chr18: g.77748604_77748637del (type 2Delta)). Hence, we identified causative recessive variants in TXNL4A in two individuals with BMKS as well as in three individuals (from two families) with isolated choanal atresia.

Este estudio describe la evolución del diagnóstico pre y postnatal del síndrome de Down (SD) en la Comunidad Foral de Navarra desde 1991 a 2009 y analiza su impacto preventivo a nivel poblacional, así como los cambios asociadas a dicha cromosomopatía. En ausencia de diagnóstico prenatal del SD, el cambio en la edad materna desde 1991 a 2009 hubiera conllevado un aumento del 50% en el número de nacimientos con esta cromosomopatía. Sin embargo, el incremento de la tasa de detección prenatal (15,8% durante 1991-1994 y 64,3% entre 2006-2009) ha condicionado una ligera tendencia descendiente de su prevalencia al nacimiento, no estadísticamente significativa, y un aumento en la edad media de sus madres (32,75± 5,02 y 34,8±4,82 años en el primer y último periodos, respectivamente). El porcentaje de SD nacidos vivos, hijos de madres menores de 35 años, fue del 66% en 1991-2004 y del 45% en 2006-2009. Casi una quinta parte de las gestantes rechazaron el cribado bioquímico o la amniocentesis y un 17% de los nacimientos con SD tuvieron un resultado de cribado positivo, pero las madres decidieron continuar el embarazo. Estos resultados sugieren que, a pesar de implementar nuevos y más sensibles test de cribado, la incidencia del SD puede mantenerse relativamente alta en nuestra población, circunstancia a tener en cuenta tanto en la elaboración de los planes de prevención antenatal como de los de su cuidado postnatal. This study describes the development of pre and postnatal diagnosis of sindrome de Down (SD) in the Autonomous Community of Navarre from 1991 to 2009 and assesses its preventive impact in the population, as well as to associated socio-demographic changes. In the absence of a prenatal diagnosis for DS, the change in maternal age from 1991 to 2009 would have caused a 50% increase in births with this disorder. However, the antenatal rate detection of DS increased from 15.8% in 1991-4 to 64.3% in 2006-9, giving rise to a decreasing incidence trend, not statistically significant, during the study period and to a higher mean age of mothers of live births with DS (32.75± 5,02 and 34.8±4,82 years during the first and second periods of the study, respectively). The proportion of young mothers (