A 35-year-old woman, gravida 1 para 0, at 20 weeks gestation comes to the office for a routine prenatal visit and fetal anatomy ultrasound. The ultrasound reveals several abnormalities. An amniocentesis is performed and a fetal karyotype analysis is ordered; the results are shown in the image below: This fetus is at greatest risk for developing which of the following conditions after birth?

Question

A 35-year-old woman, gravida 1 para 0, at 20 weeks gestation comes to the office for a routine prenatal visit and fetal anatomy ultrasound.  The ultrasound reveals several abnormalities.  An amniocentesis is performed and a fetal karyotype analysis is ordered; the results are shown in the image below:  This fetus is at greatest risk for developing which of the following conditions after birth?

Quizplus · Accepted Answer

11ec160b_3766_872c_9249_1949c01e9cdf_MD0001_00 This karyotype shows trisomy 21 (47, XY, +21), which is diagnostic for Down syndrome. This condition usually results from meiotic nondisjunction in the ovum, with advanced maternal age (age ≥35) as a risk factor. Prenatal diagnosis is often suspected based on associated ultrasound findings, including a thickened nuchal fold, cardiac septal defects, and/or gastrointestinal abnormalities (eg, duodenal atresia). Down syndrome is the most common genetic cause of intellectual disability. In addition, Down syndrome significantly increases the risk of childhood hematologic malignancies, including acute lymphoblastic leukemia (most common leukemia in patients with Down syndrome) and acute megakaryoblastic leukemia. The pathogenesis of the increased leukemia risk is uncertain, but may involve increased chromosome 21 gene expression promoting overall genomic instability. (Choice B) Patients with Fanconi anemia, not Down syndrome, develop bone marrow failure (aplastic anemia) due to an inherited mutation that causes defective DNA repair. Karyotype analysis would be normal in this condition. (Choice C) Chronic myelogenous leukemia is commonly associated with a reciprocal translocation between the long arms of chromosomes 9 and 22 (ie, Philadelphia chromosome). This translocation fuses the BCR gene on chromosome 22 to the ABL gene on chromosome 9, resulting in formation of the oncogenic BCR-ABL fusion gene. Unlike this case, karyotype analysis would show elongation of chromosome 9 and shortening of chromosome 22. (Choice D) Turner syndrome (45, XO) and Klinefelter syndrome (47, XXY) increase the risk of ovarian germ cell tumors and extragonadal germ cell tumors, respectively. This patient's karyotype is inconsistent with these diagnoses, and germ cell tumors are not increased in patients with Down syndrome. (Choices E and F) Incidence of retinoblastoma, which is associated with a retinoblastoma (RB1) gene mutation, and rhabdomyosarcoma is not increased in patients with Down syndrome. Educational objective: Trisomy 21 (which is diagnostic for Down syndrome) is detectable by cytogenetic karyotype analysis. Patients are at increased risk of developing hematologic malignancies, including acute lymphoblastic leukemia and acute megakaryoblastic leukemia. __________ References: The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/27285583) Transient abnormal myelopoiesis and AML in Down syndrome: an update. (http://www.ncbi.nlm.nih.gov/pubmed/27510823)

A 35-Year-Old Woman, Gravida 1 Para 0, at 20 Weeks