This week, we are sharing another USMLE® Step 1-style practice question to test your knowledge of medical topics. Today’s case focuses on a 5-month-old female infant that is admitted to the pediatric intensive care unit for surgical treatment of preductal coarctation of the aorta. During subsequent evaluation, the patient is found to have a horseshoe kidney as well as lymphedema affecting the hands and feet. The patient has low set ears. Which of the following is the most likely genetic aberration that led to this patient’s presentation? Can you figure it out?
A 5-month-old female infant is admitted to the pediatric intensive care unit for surgical treatment of preductal coarctation of the aorta. The patient is stable and afebrile. Blood pressure is 70/50 mmHg, and respiratory rate is 34/min. During subsequent evaluation, the patient is found to have a horseshoe kidney as well as lymphedema affecting the hands and feet. The patient has low set ears. Which of the following is the most likely genetic aberration that led to this patient’s presentation?
A. Nondisjunction event during meiosisB. Nondisjunction event during mitosis
C. Partial loss of chromosome during mitosis
D. Nondisjunction resulting in Trisomy 21
E. Nondisjunction resulting in Trisomy 18
Scroll down to find the answer!
The correct answer to today’s USMLE® Step 1 Question is…
A. Nondisjunction event during meiosis
Before we get to the Main Explanation, let’s look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!
Incorrect answer explanations
The incorrect answers to today’s USMLE® Step 1 Question are…
B. Nondisjunction event during mitosis
Incorrect: While this event would also result in Turner syndrome, it would result in a mosaic form of the condition. The mosaic form of Turner syndrome has far less severe symptoms due to the expression of normal 46 XX chromosomes in some cells. In contrast, the patient in this vignette has multiple congenital abnormalities and likely has a uniform genotype of 45 XO within all cells.
C. Partial loss of chromosome during mitosis
Incorrect: This event would also result in a mosaic form of Turner syndrome, which is far less severe due to the expression of normal 46 XX chromosomes in some cells. This patient has the severe form, as demonstrated by the multiple congenital abnormalities, and likely has a uniform genotype of 45 XO within all cells.
D. Nondisjunction resulting in Trisomy 21
Incorrect: Individuals with Trisomy 21 can present with low set ears, a single palmar crease, short ears, and short neck. While individuals with trisomy 21 may develop cardiac defects (e.g. atrioventricular septal defects), the condition is not typically associated with coarctation of the aorta.
E. Nondisjunction resulting in Trisomy 18
Incorrect: Edwards syndrome can present with clenched hands, an abnormally small head, underdeveloped jaw, and rocker bottom feet. However, the condition would not typically present with the combination of coarctation of the aorta, lymphedema, and horseshoe kidney.
Main Explanation
This vignette describes a female infant with several congenital anomalies, namely preductal coarctation of the aorta, horseshoe kidney, and lymphedema. These findings are suggestive of Turner syndrome.
Answering this question requires an understanding of the different types of chromosomal abnormalities present within Turner syndrome (see table below). A complete lack of Y chromosomal inheritance, which often occurs due to a nondisjunction during meiosis of the paternal gamete, would lead to the 45 XO genotype. Affected patients will present with the most severe form of Turner syndrome and likely have multiple congenital anomalies, as in the case of this patient.
In contrast, if Turner syndrome were to develop due to nondisjunction during mitosis, then chromosomal mosaicism would develop. Chromosomal mosaicism means that different cells in the patient’s body will have varying genotypes (e.g., 45 XO, 46 XX).Clinical features of Turner syndrome include a female phenotype with webbed neck, shield chest, short stature, lymphedema, nail dysplasia, and high-arched palate. Turner syndrome presents with gonadal dysgenesis and streak ovaries, which results in insufficient estrogen production. As a result, patients can have delayed puberty, primary amenorrhea, osteoporosis, and infertility. Furthermore, patients are at risk for coarctation of the aorta and renal malformations.
Major Takeaway
Turner syndrome can be caused by nondisjunction during meiosis or mitosis, leading to a 45 XO or mosaic 45 XO/46 XX karyotype, respectively. There are many developmental abnormalities associated with Turner syndrome, including a webbed neck, shield chest, streak ovaries, coarctation of the aorta, and renal malformations.
References
Kesler, S.R. (2007) Turner syndrome. Child and Adolescent Psychiatric Clinics of North America. 16(3), 709-722. Doi: 10.1016/j.chc.2007.02.004.Kikkeri, N.S., Nagalli, S. (2021) “Turner syndrome”. StatPearls [Internet]. Web Address: https://www.ncbi.nlm.nih.gov/books/NBK554621/.
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