Prenatal diagnosis of complex phenotype in a 13-week-old fetus with an interstitial multigene deletion 20q13.13.-q13.2 by chromosomal microarray

We report the first trimester three-dimensional ultrasonographic findings in a 13-week-old fetus with complex phenotype and a de novo 4.7 Mb multigene deletion encompassing chromosome region 20q13.13-q13.2 detected by chromosomal microarray. Fetal sonography detected radial-ray anomalies in the form of bilateral absence of thumbs and the left club hand deformity. The presence of single atrioventricular canal instead of the atrial septal defect typical for Holt-Oram syndrome pointed us to rather suspect the SALL4 related diseases. Central nervous system anomaly in the form of enlarged lateral brain ventricles with choroid plexus shifted backwards was not previously reported as a part of SALL4 related disorders. The pregnancy was terminated at 14 + 3 weeks of pregnancy and the autopsy confirmed ultrasonographic findings. Deleted region included 38 genes, where only SALL4, ADNP and KCNB1 heterozygote pathogenic variants were described to be cause of syndromic forms. Radial ray anomalies are common part of clinical picture of SALL4 related disorders. Despite the lack of prenatally described cases, we hypothesized that maldevelopment of lateral brain ventriculomegaly could be very early sonographic sign of disturbed ADNP expression causing Helsmoortel-Van der Aa syndrome, but in some extent also of KCNB1 related early-onset epileptic encephalopathy. Furthermore, the possible dosage-dependent influence of recessive genes located in this region cannot be also excluded. The use of genome-wide technologies enables the detection of subtle chromosomal imbalances and more precise familial genetic counseling regarding actual and future pregnancies.     

Issues with implementing a high‐quality lung cancer screening program

Answer questions and earn CME/CNE After a comprehensive review of the evidence, the United States Preventive Services Task Force recently endorsed screening with low‐dose computed tomography as an early detection approach that has the potential to significantly reduce deaths due to lung cancer. Prudent implementation of lung cancer screening as a high‐quality preventive health service is a complex challenge. The clinical evaluation and management of high‐risk cohorts in the absence of symptoms mandates an approach that differs significantly from that of symptom‐detected lung cancer. As with other cancer screenings, it is essential to provide to informed at‐risk individuals a safe, high‐quality, cost‐effective, and accessible service. In this review, the components of a successful screening program are discussed as we begin to disseminate lung cancer screening as a national resource to improve outcomes with this lethal cancer. This information about lung cancer screening will assist clinicians with communications about the potential benefits and harms of this service for high‐risk individuals considering participation in the screening process. CA Cancer J Clin 2014;64:351–363. © 2014 American Cancer Society.