{'fraction_non_alphanumeric': 0.0249119275289381, 'fraction_numerical': 0.02214393558127831, 'mean_word_length': 5.004531722054381, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Complexity of noninvasive prenatal screening and diagnostic testing for an unbalanced translocation involving chromosomes 5 and 18

The introduction of noninvasive prenatal screening (NIPS) to clinical practice has had a significant impact on testing options for prenatal aneuploidy detection. However, as the path toward prenatal diagnosis is shifting, the distinction between screening and diagnostic testing and the importance of a precise diagnosis remain unchanged. The case we present highlights these concepts and the limitations of both NIPS and the routinely used fluorescent in situ hybridization (FISH) in the diagnosis of a complex chromosome abnormality. Our patient was a 30-year-old G1P0 woman of Hispanic descent, who presented for a fetal anatomy ultrasound at 27weeks and 4 days gestation. Her pregnancy was reported as uncomplicated thus far. The patient and her partner reported no significant family history of birth defects, mental retardation, or recurrent miscarriages. Reports obtained after the visit confirmed that ultrasounds at 16weeks and 1 day, and 22weeks and 3 days noted a limited examination of fetal anatomy because of fetal position, and no gross anomalies. A quad screen had been performed at 18weeks and 2 days with screen negative results. The patient’s maternal serum markers were all low (alpha-fetoprotein 0.59 MoM, human chorionic gonadotropin 0.62 MoM, unconjugated estriol 0.55 MoM, inhibin 0.92 MoM); however, the calculated risk for Trisomy 18 was 1 in 951. On the patient’s first ultrasound at our institution, a fetal head circumference in the third percentile and abdominal circumference in the tenth percentile were visualized. On follow up at 28weeks and 5days, the ultrasound revealed polyhydramnios, a ventricular septal defect and suspicion of other heart defects, clenched hands, growth delay, and a cistern magna in the upper limits of normal. The patient was offered diagnostic testing for chromosome abnormalities via amniocentesis to clarify the diagnosis and prognosis for the pregnancy. The patient planned to continue the pregnancy, was concerned about the risk of preterm delivery, and therefore declined diagnostic testing. Given the clinical suspicion for Trisomy 18, the patient was also offered NIPS and elected to pursue the Harmony Prenatal Test through Ariosa Diagnostics. Although not diagnostic, the analysis of cell-free DNA from maternal plasma is reported to have a sensitivity of 97.4% for Trisomy 18 and a false positive rate of 0.07%. At 30weeks and 5days gestation, results from the NIPS were high risk for Trisomy 18, indicating a greater than 99% probability that the fetus had Trisomy 18. The fetal fraction in the patient’s blood was 21%. The patient was informed of the results, she declined having an amniocentesis for diagnostic confirmation, and the pregnancy was followed with a high suspicion for Trisomy 18. The patient missed several prenatal follow up visits, but returned at 38weeks. A fetal echo was performed, which showed a ventricular septal defect (VSD), but was limited by gestational age and fetal position. A plan for induction of labor at 40weeks was agreed to. When the patient returned at 40weeks, she had changed her mind about amniocentesis, the procedure was completed, and fluid was sent for FISH analysis of chromosomes 13, 18, 21, X, and Y. The results were ready within 24h and, surprisingly, were normal. FISH was repeated as there was uncertainty about the quality of the amniotic fluid sample, and results again were normal. Consultation with Ariosa regarding this discordance revealed the result may be due to a chromosome 18 rearrangement or duplication. At this point, labor was in progress, and the baby girl was born via C-section because of a non-reassuring fetal heart rate and intolerance of labor. The baby weighed 1940 g at delivery, was 40 cm in length, and had a head circumference of 30 cm (all below third percentile). She had Apgar scores of 6