RESUMEN
Isolated congenital diaphragmatic hernia is often a sporadic event with a low recurrence risk. However, underlying genetic etiologies, such as chromosome anomalies or single gene disorders, are identified in a small number of individuals. We describe two fetuses with a unique pattern of multiple congenital anomalies, including diaphragmatic hernia, short bowel and asplenia, born to first-cousin parents. Whole exome sequencing showed that both were homozygous for a missense variant, c.950A>C, predicting p.Asp317Ala, in the H.20-Like Homeobox 1 (HLX1) gene. HLX is a homeobox transcription factor gene which is relatively conserved across species. Hlx homozygous null mice have a short bowel and reduced muscle cells in the diaphragm, closely resembling the anomalies in the two fetuses and we therefore suggest that the HLX mutation in this family could explain the fetal findings.
Asunto(s)
Hernias Diafragmáticas Congénitas/genética , Síndrome de Heterotaxia/genética , Proteínas de Homeodominio/genética , Síndrome del Intestino Corto/genética , Factores de Transcripción/genética , Anomalías Múltiples/genética , Anomalías Múltiples/fisiopatología , Animales , Anomalías del Sistema Digestivo/genética , Anomalías del Sistema Digestivo/fisiopatología , Predisposición Genética a la Enfermedad , Hernias Diafragmáticas Congénitas/fisiopatología , Síndrome de Heterotaxia/fisiopatología , Humanos , Ratones , Mutación , Análisis de Secuencia de ADN , Síndrome del Intestino Corto/fisiopatología , Secuenciación del ExomaRESUMEN
OBJECTIVES: The objective of this study is to describe the prenatal sonographic features and the results of DNA analysis on three fetuses with dyssegmental dysplasia, Silverman-Handmaker type (DD-SH). METHODS: A retrospective review of three fetuses with confirmed DD-SH was conducted. The fetal ultrasound findings, the radiological characteristics, and the results of the mutation analysis of the heparan sulphate perlecan gene 2 (HSPG2) were reviewed. RESULTS: There were three cases in two families with DD-SH diagnosed prenatally. The main prenatal ultrasound and the radiological features of DD-SH were severe limb shortening and vertebral segmentation and fusion defects (anisospondyly). The DNA analysis of the HSPG2 gene showed that the two affected fetuses in a nonconsanguineous family had a compound heterozygote for the c.646G > T transversion in exon 7 and a c.5788C > T transition in exon 46. The fetus born to the consanguineous couple had a homozygous mutation c.1356-27_1507 + 59del. CONCLUSION: DD-SH can be diagnosed prenatally using fetal ultrasound as early as 13 weeks. Xrays and DNA analysis of the HSPG2 gene are important for the confirmation of the diagnosis and for the preimplantation and prenatal diagnosis in pregnancies at risk.
Asunto(s)
Enanismo/diagnóstico por imagen , Enanismo/genética , Aborto Eugénico , Adulto , Femenino , Humanos , Técnicas de Diagnóstico Molecular , Embarazo , Estudios Retrospectivos , Mortinato , Ultrasonografía Prenatal , Adulto JovenAsunto(s)
Listeriosis/complicaciones , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , Ampicilina/uso terapéutico , Antibacterianos/uso terapéutico , Femenino , Gentamicinas/uso terapéutico , Humanos , Recién Nacido , Enfermedades del Recién Nacido/tratamiento farmacológico , Enfermedades del Recién Nacido/microbiología , Transmisión Vertical de Enfermedad Infecciosa , Listeriosis/transmisión , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/diagnósticoAsunto(s)
Anomalías Múltiples/genética , Riñón/anomalías , Síndrome de Smith-Lemli-Opitz/diagnóstico , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/patología , Aborto Inducido , Femenino , Deformidades Congénitas del Pie/genética , Deformidades Congénitas del Pie/patología , Humanos , Oligohidramnios/diagnóstico , Polidactilia/genética , Polidactilia/patología , Embarazo , Sindactilia/genética , Sindactilia/patología , UltrasonografíaRESUMEN
BACKGROUND: Varicella Zoster virus (VZV) infection is potentially very serious in bone marrow transplant recipients, and may manifest as a disseminated visceral infection. This condition is generally accompanied by a vesicular rash. OBJECTIVES: We review here a case of fulminant fatal disseminated VZV infection, not accompanied by skin involvement, and the laboratory approaches currently available to diagnose this disease. STUDY DESIGN: Post mortem tissue samples were subjected to histopathological examination, and tested for herpesviruses by electron microscopy and PCR. RESULTS: Intranuclear inclusions were noted by histological examination in the lungs, liver, kidneys and bone marrow. Particles with a herpesvirus morphology were visualized in liver tissue. VZV DNA was detected in liver and bone marrow by PCR followed by sequencing of the amplicons. Viremia was documented by retrospective testing of the serum by PCR. CONCLUSIONS: A disseminated VZV infection which proved rapidly fatal was demonstrated in a case without skin manifestations. This rare presentation of VZV infection is potentially underdiagnosed. Testing for VZV viremia by PCR can at the very least suggest the diagnosis although whether plasma-associated viremia is truly pathognomonic of visceral disseminated infection remains to be established.