First-trimester septated cystic hygroma, marked non-immune fetal hydrops, 45,X and coarctation of the aorta with neonatal survival.

Marked first-trimester nonimmue hydrops fetalis and 45,X with neonatal survival.

Current Perspectives of Prenatal Cell-free DNA Screening in Clinical Management of First-Trimester Septated Cystic Hygroma.

First-trimester septated cystic hygroma occurs in approximately 1 in 268 pregnancies and has long been associated with a markedly increased risk of fetal aneuploidy and, among euploid fetuses, an increased risk of structural anomalies primarily affecting the cardiac and skeletal systems. Invasive prenatal diagnosis - chorionic villus sampling and/or amniocentesis - encompasses the time-honored clinical tools for the next step in management following prenatal sonographic diagnosis of first-trimester septated cystic hygroma. Currently, prenatal cell-free DNA (cfDNA) screening for fetal aneuploidy with select microdeletions is gradually replacing the considerably less sensitive, and labor-intensive combined first-trimester screening. These new technologies have opened potential new venues in the clinical management of this ominous late first-trimester sonographic diagnosis. Advances in cfDNA technologies are now permitting detection of chromosomal copy number variants (CNV) larger than 7Mb across genome and select serious single-gene disorders (mainly impacting skeletal and neurological development), affecting quality of life and may benefit from medical and/or surgical management. This commentary will address the available non-invasive prenatal screening technologies, which clearly enhance immediate genetic analysis modalities applicable in the presence of the complex sonographic finding of first-trimester septated cystic hygroma.

Mid-trimester dilated fetal bowel leading to diagnosis of interstitial duplication 46,XX,dup(8)(q21.13q21.2) associated with extensive neonatal jejuno-ileal atresia.

Small bowel atresia constitutes congenital obstruction of the lumen of the duodenum, jejunum or ileum, and is one of the most common causes of neonatal bowel obstruction with a reported incidence of between 1.3 and 2.8 per 10,1000 live births. Complete absence of the small bowel, or near total jejuno-ileal atresia (in the absence of malrotation or gastroschisis), are extremely rare. Mid-trimester prenatal sonographic finding of dilated fetal bowel led to the finding of interstitial 8q21.13q21.2 duplication. Following delivery at 32 weeks' gestation, at laparotomy almost complete small bowel atresia was noted. Anastomosis between the existing small bowel and colon was performed. At 7 months of age, the infant continued to receive total parenteral nutrition supplemented by gastrostomy and oral-spoon formula feeding, and weighed 7 kg (50th centile). This is the first report of the association interstitial 8q21.13q21.2 duplication, which includes OMIM genes (RALYL, LRRCC1, and E2F5) and extensive small bowel atresia.

Mid-trimester isolated bilateral rocker bottom feet leading to prenatal diagnosis of 7q11.23 microdeletion: Williams syndrome.

Prenatal sonographic depiction of congenital vertical talus (rocker bottom feet), describing a prominent calcaneus and rounded convex appearance of the ventral aspect of the foot, has been reported with fetal Trisomies 18, 13, 9 HOXD10 mutations and recently 2q13 microdeletion. We present a 24 year old in whom mid-trimester sonographic finding of isolated bilateral rocker bottom feet led to diagnosis of 7q11.23 microdeletion-Williams syndrome. This association has not been reported previously. This case emphasizes the critical assessment of detail microarray upon prenatal sonographic notation of abnormal structural fetal features.

Mid-trimester absent nasal bone and transient unilateral hydronephrosis associated with 16p13.3 microduplication.

Characteristic phenotypic features of 16p13.3 microduplication include impaired mental development, arthrogryposis-like musculoskeletal anomalies (club-feet, congenital hip dislocation, and camptodactyly of fingers and toes), facial dysmorphology, and at times congenital cardiac disease. Most of the described affected individuals have microduplications involving the CREBBP gene. Findings indicate this gene to be dosage-sensitive and likely involved in the phenotypes of 16p13.3 microduplication syndrome. We describe the incidental finding of 16p13.3 microduplication in a fetus with mid-trimester sonographic examination showing absent nasal bone and transient unilateral hydronephrosis.

Direct-to-consumer genetic testing companies tell their customers to 'see a genetic counselor'. How do genetic counselors feel about direct-to-consumer genetic testing?

Professional societies, the FDA, and many direct-to-consumer genetic testing (DTC-GT) companies have highlighted the value of counseling from a medical professional with genetics expertise in order to enhance the value and minimize the risks associated with DTC-GT. However, there is limited information available identifying genetic counselors' own views on DTC-GT, their willingness to counsel consumers based on DTC-GT results, and their experiences to date seeing DTC-GT consumers in a clinical setting. We surveyed genetic counselors accessed through mailing lists associated with the National Society of Genetic Counselors (NSGC) and the American Board of Genetic Counseling (ABGC). Response rate was estimated to be 12.2% (n = 482). A majority of all respondents (56.4%, n = 263) described themselves as feeling negatively or very negatively toward DTC-GT; only 6.9% (n = 32) described themselves as feeling positively or very positively. While 90.9% of respondents (n = 398) believed that DTC-GT would be improved with the involvement of genetic counselors, only 31.2% agreed or strongly agreed that they are comfortable providing counseling to DTC-GT consumers (n = 142). Clinical counseling of DTC-GT consumers is not routine but it is also not uncommon; 40.1% of all respondents (n = 189) have seen at least one consumer in clinic for the sole purpose of reviewing DTC-GT results. The results of our study suggest that most respondents would be more accepting of DTC-GT if genetic counseling was a part of the process, but the majority of counselors do not feel comfortable providing this service.

Mid-trimester fetal facial dysmorphology associated with 2p25.3 microdeletion.

We describe unusual mid-trimester sonography of subtle fetal facial dysmorphic features including; flattened nasofrontal angle with an almost vertically positioned nasal bone, acute nasolabial angle, and convexity of the maxillary areas in a fetus with otherwise normal anatomy. Microarray identified a 64.5 KB interstitial deletion of 2q25.3, which includes one exon of MYT1L. Mutations and deletions in MTY1L have been associated with autosomal dominant intellectual disability, autistic features, and obesity. Association of these features and 2p25.3 microdeletion has not been reported previously. This case emphasizes the importance of detailed microarray analysis following the sonographic recognition of subtle fetal dysmorphic features.