RESUMEN
OBJECTIVES: To describe macroscopic and microscopic anomalies present in fetuses carrying hepatocyte nuclear factor-1 ß mutation, their frequency, and genotype/phenotype correlations. METHODS: Clinical data, ultrasound findings, genetic studies, and autopsy reports of 20 fetal autopsies were analyzed. Histology was reviewed by two pathologists. RESULTS: Macroscopic findings were typically unilateral or bilateral renal enlargement and cortical cysts. Renal lesions were associated with congenital anomalies of the kidney and urinary tract in 25% of cases. Microscopic renal anomalies were dominated by glomerulocystic kidney and renal dysplasia. Extra-renal manifestations such as pancreatic hypoplasia (75%) and genital anomalies (68%) were only detected at autopsy. In 40% of cases, there was heterozygous deletion of the whole gene. There were de novo mutations in 40%. CONCLUSION: This study underlines the importance of considering hepatocyte nuclear factor-1 ß mutations in fetuses with congenital anomalies of the kidney and urinary tract, especially when associated with pancreatic hypoplasia. No correlation between phenotype and genotype was found, highlighting high intra-familial variability in cases with inherited mutations. © 2016 John Wiley & Sons, Ltd.
Asunto(s)
Factor Nuclear 1-beta del Hepatocito/genética , Riñón/anomalías , Páncreas/anomalías , Enfermedades Pancreáticas/congénito , Anomalías Urogenitales/genética , Autopsia , Anomalías Congénitas/diagnóstico por imagen , Anomalías Congénitas/genética , Anomalías Congénitas/patología , Femenino , Genotipo , Humanos , Riñón/diagnóstico por imagen , Riñón/patología , Masculino , Mutación , Páncreas/diagnóstico por imagen , Enfermedades Pancreáticas/diagnóstico por imagen , Enfermedades Pancreáticas/genética , Fenotipo , Embarazo , Ultrasonografía Prenatal , Anomalías Urogenitales/diagnóstico por imagen , Anomalías Urogenitales/patologíaRESUMEN
We report a 29-week male fetus with healthy consanguineous parents. He showed a severe sclerosing bone disorder affecting all skeletal elements, resulting in insufficient modeling, generalized densification, and fragility of the skeleton. This skeletal dysplasia was associated with an abnormal craniofacial development (hypertelorism, severe microretrognathia, cleft palate, absent epiglottis, reduced number, and mineralization of teeth buds) and abnormal terminal phalanges. Neuropathologic examination showed bilateral fronto-parietal cerebral polymicrogyria. This syndrome appears to represent a new variant of congenital sclerotic bone disorder of unknown origin. Autosomal recessive inheritance is possible.
