RESUMEN
Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is caused by de novo loss-of-function variants in the SON gene (MIM #617140). This multisystemic disorder is characterized by intellectual disability, seizures, abnormal brain imaging, variable dysmorphic features, and various congenital anomalies. The wide application and increasing accessibility of whole exome sequencing (WES) has helped to identify new cases of ZTTK syndrome over the last few years. To date, there have been approximately 45 cases reported in the literature. Here, we describe 15 additional individuals with variants in the SON gene, including those with missense variants bringing the total number of known cases to 60. We have reviewed the clinical and molecular data of these new cases and all previously reported cases to further delineate the most common as well as emerging clinical findings related to this syndrome. Furthermore, we aim to delineate any genotype-phenotype correlations specifically for a recurring pathogenic four base pair deletion (c.5753_5756del) along with discussing the impact of missense variants seen in the SON gene.
Asunto(s)
Anomalías Congénitas/genética , Proteínas de Unión al ADN/genética , Discapacidad Intelectual/genética , Antígenos de Histocompatibilidad Menor/genética , Convulsiones/genética , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Anomalías Congénitas/diagnóstico , Anomalías Congénitas/patología , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/patología , Masculino , Mutación Missense/genética , Fenotipo , Convulsiones/diagnóstico , Convulsiones/patología , Secuenciación del ExomaRESUMEN
INTRODUCTION: Detecting critical congenital heart disease (CCHD) by prenatal ultrasound and routine examination of newborns is insufficient, and pulse oximetry screening (POS) has been recommended. POS has been implemented by some Danish maternity wards but not by all. However, no Danish studies of POS have been published. This study evaluates the first year with POS at Kolding Hospital, the Southern Region of Denmark. METHODS: All apparently healthy newborns were offered POS few hours postpartum. Both pre- and post-ductal POS were carried out using a well-known protocol and registered as POS approved; POS repeated and approved; or POS not approved, paediatrician called. Paediatricians registered clinical data, and general experiences regarding POS were collected. RESULTS: POS was performed in 2,855 newborns; 2,715 were approved immediately, 81 were repeated. Paediatric assistance was required for 59 newborns; 16 could stay in the maternity ward following assessment, while 18 were admitted for observation until their saturation normalised. One newborn had CCHD, while ten had other conditions needing treatment and 14 had more benign respiratory disorders. One sick newborn would not have been picked up by post-ductal screening only. No midwives performing the screening and no parents refrained from POS. CONCLUSIONS: Early POS as part of the routine examination few hours postpartum seemed natural to midwives and parents but induced an increased false-positive rate. Early POS may discover other serious conditions in time for intervention. FUNDING: none. TRIAL REGISTRATION: none.
Asunto(s)
Cardiopatías Congénitas/diagnóstico , Tamizaje Neonatal/métodos , Oximetría/métodos , Dinamarca , Femenino , Humanos , Recién Nacido , MasculinoRESUMEN
The angiogenic factor ratio soluble Fms-kinase 1 (sFlt-1)/placental growth factor (PlGF) is a novel diagnostic tool for preeclampsia. We compared the efficacy of the KRYPTOR (BRAHMS) automated assays for sFlt-1 and PlGF with the Elecsys (Roche) assays in a routine clinical setting. Preeclamptic women (n = 39) were included shortly after the time of diagnosis. Normotensive control pregnancies were matched by gestational age (n = 76). The KRYPTOR assays performed comparably or superior to Elecsys (sFlt-1/PlGF area under the curve 0.746 versus 0.735; P = .09; for non-obese 0.820 versus 0.805, P = .047). For early-onset preeclampsia, KRYPTOR area under the curve increased to 0.929 with a 100% specificity for preeclampsia at cut-off 85 and an 88.9% sensitivity for preeclampsia at cut-off 33. For women with preeclampsia and preterm delivery or Hemolysis, Elevated Liver enzymes, Low Platelet count (HELLP) syndrome, the KRYPTOR sFlt-1/PlGF ratio was manifold increased (P < .01). The sFlt-1/PlGF ratio proved especially useful in early-onset preeclampsia, preeclampsia with preterm delivery or HELLP, and among non-obese women.