A 1-day-old infant in the newborn nursery is found to have a harsh, holosystolic murmur on physical examination. The neonate was born at 39 weeks gestation to a 36-year-old woman who opted to defer prenatal screening. Review of medical records shows no family history of genetic or chromosomal disorders. The infant's vital signs are appropriate for his age. The rest of the physical examination shows a flat facial profile, protruding tongue, and small ears. Which of the following most likely occurred prior to conception?

Question

A 1-day-old infant in the newborn nursery is found to have a harsh, holosystolic murmur on physical examination.  The neonate was born at 39 weeks gestation to a 36-year-old woman who opted to defer prenatal screening.  Review of medical records shows no family history of genetic or chromosomal disorders.  The infant's vital signs are appropriate for his age.  The rest of the physical examination shows a flat facial profile, protruding tongue, and small ears.  Which of the following most likely occurred prior to conception?

Quizplus · Accepted Answer

11ec160b_3755_48fd_9249_7518c322847d_MD0001_00 During normal meiosis, homologous chromosomes separate to pass on individual chromatids to daughter cells. In meiotic nondisjunction, the chromosomes fail to separate, allowing one or more daughter cells to pass on with an extra copy of a chromosome. Increasing maternal age, particularly age >35, is associated with an elevated risk of nondisjunction that is likely due to cumulative oxidative stress, depletion of available mature oocytes, and shortening of oocyte telomeres. From highest to lowest prevalence, the most common consequences of maternal nondisjunction are trisomies 21 (Down syndrome), 18 (Edwards syndrome), and 13 (Patau syndrome). Less than 5% of Down syndrome cases are caused by a Robertsonian translocation (Choice B), which results from a break near the centromeres of 2 chromosomes (eg, chromosomes 14 and 21) and subsequent transfer of genetic material between these chromosomes. This translocation results in 46 chromosomes in the fetus with 3 effective copies of chromosome 21. Classic features of Down syndrome include a flat facial profile, epicanthal folds, upslanting palpebral fissures, protruding tongue, and small ears. Congenital heart defects (eg, complete atrioventricular defect, ventricular or atrial septal defect) are seen in 50% of patients. (Choice A) Chromosomal deletions are associated with cri-du-chat syndrome (5p deletion), DiGeorge syndrome (22q11 microdeletion), and Prader-Willi syndrome (15q deletion). Deletions are not associated with increased maternal age. (Choice C) Imprinting is the selective inactivation of a maternal or paternal allele. When a selectively expressed allele is abnormal (eg, gene deletion), conditions such as Prader-Willi syndrome (maternal inactivation/paternal deletion) or Angelman syndrome (paternal inactivation/maternal deletion) can result. (Choice E) Trinucleotide repeat expansions within DNA can dysregulate protein production, causing disorders such as Huntington disease, myotonic dystrophy, and fragile X syndrome. Educational objective: Down syndrome is most commonly caused by maternal meiotic nondisjunction, a process by which the fetus receives 3 full copies of chromosome 21. Dysmorphic features (eg, flat facial profile, protruding tongue, small ears, upslanting palpebral fissures) and cardiac defects (eg, endocardial cushion defects) are characteristic. __________ References: Maternal age and risk for trisomy 21 assessed by the origin of chromosome nondisjunction: a report from the Atlanta and National Down Syndrome Projects. (http://www.ncbi.nlm.nih.gov/pubmed/19050929) Risk factors for nondisjunction of trisomy 21. (http://www.ncbi.nlm.nih.gov/pubmed/16192705)

A 1-Day-Old Infant in the Newborn Nursery Is Found to Have