A 1-hour-old girl born to a 40-year-old woman is brought to the nursery for evaluation. The pregnancy and delivery were uncomplicated. Physical examination shows mid-face hypoplasia with a flat nasal bridge, up-slanting palpebral fissures, a small mouth, and a single palmar crease bilaterally. Cardiac auscultation reveals a blowing holosystolic murmur heard best along the sternal border. Which of the following abnormalities is most likely to be present in this patient?

Question

A 1-hour-old girl born to a 40-year-old woman is brought to the nursery for evaluation.  The pregnancy and delivery were uncomplicated.  Physical examination shows mid-face hypoplasia with a flat nasal bridge, up-slanting palpebral fissures, a small mouth, and a single palmar crease bilaterally.  Cardiac auscultation reveals a blowing holosystolic murmur heard best along the sternal border.  Which of the following abnormalities is most likely to be present in this patient?

Quizplus · Accepted Answer

11ec160b_375f_823e_9249_b7695bc93436_MD0001_00 This child has many of the characteristic features of Down syndrome (DS), a condition that results from an increased gene dosage effect due to an extra copy of chromosome 21. Three cytogenetic abnormalities can lead to DS: Meiotic nondisjunction accounts for nearly 95% of DS cases. Failure of homologous chromosomes or sister chromatids to separate during meiosis can result in the inheritance of 3 copies of chromosome 21 in one daughter cell (trisomy) and 1 copy in the other daughter cell (monosomy). Nondisjunction during meiosis is almost always of maternal origin. Unbalanced translocations account for 2%-3% of DS cases. These individuals have 46 chromosomes, but have extra genetic material (consisting of duplicate chromosome 21 genes) attached to one of their chromosomes. Approximately one third of these cases are due to a balanced translocation in one parent, which confers a high recurrence risk. Mosaicism accounts for <2% of DS cases. Affected individuals have 2 distinct cell lines as a result of nondisjunction during mitosis: one with a normal genotype and one with trisomy 21. The proportion of affected cells determines the severity of DS features. Of the available answer options, only mosaicism is consistent with a third copy of chromosome 21 existing in at least a portion of the patient's cells. (Choices A and E) Genomic imprinting is a normal process that refers to selective activation of gene expression depending on the parent of origin. Aberrant imprinting occurs with uniparental disomy, or when a person receives 2 copies of a chromosome from the same parent and no copy from the other parent. Prader-Willi syndrome and Angelman syndrome (15q) are examples of conditions caused by dysfunctional imprinting due to uniparental disomy. (Choice C) Many genetic syndromes are caused by deletions (loss of genetic material). Cri du chat syndrome (5p deletion) is an example of a syndrome caused by a partial deletion of chromosome 5. (Choice D) Increased trinucleotide repeats (triplet expansion) on certain genes can lead to silencing of a gene or synthesis of an abnormal gene product. Huntington disease and fragile X syndrome are examples of conditions caused by triplet expansion. Educational objective: Common findings in Down syndrome include cognitive impairment, facial dysmorphism, and cardiac defects; 95% of cases are caused by the presence of an extra chromosome 21 (trisomy) resulting from nondisjunction. Unbalanced Robertsonian translocations or mosaicism are less common causes. __________ References: A parent's guide to the genetics of Down syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/19212162) Mosaicism for trisomy 21: a review. (http://www.ncbi.nlm.nih.gov/pubmed/25412855)

A 1-Hour-Old Girl Born to a 40-Year-Old Woman Is Brought