Genetic disorders — MCQs

10 questions

A genetic counselor sees a family for the first time for genetic assessment. The 24-year-old businessman and his 19-year-old sister are concerned about having a mutant allele and have decided to get tested. Their grandfather and great aunt both have Huntington’s disease which became apparent when they turned 52. Their father who is 47 years old appears healthy. The geneticist discusses both the benefits and risks of getting tested and orders some tests. Which of the following tests would best provide evidence for whether the siblings are carriers or not?

A 12-year-old boy develops muscle weakness and pain, vomiting, seizures, and severe headache. Additionally, he presents with hemiparesis on one side of the body. A muscle biopsy shows 'ragged red fibers'. What is true about the mode of inheritance of the disease described?

A 32-year-old woman comes to the physician for genetic consultation. She has a history of recurrent generalized seizures, diffuse muscular weakness, and multiple episodes of transient left-sided paresis. She has been hospitalized several times for severe lactic acidosis requiring intravenous fluid hydration. Her 10-year-old daughter also has seizures and muscle weakness. Her 7-year-old son has occasional muscle weakness and headaches but has never had a seizure. Pathologic examination of a biopsy specimen from the woman's soleus muscle shows ragged-appearing muscle fibers. Genetic analysis of the patient's son is most likely to show which of the following?

A 23-year-old woman and her husband come to a genetic counselor because she is concerned about the chance of having an inherited defect if they had a child. Family history reveals no significant family history in her husband; however, her sister had a son who has seizures, failure to thrive, and neurodegeneration. She does not remember the name of the disease but remembers that her nephew had sparse, brittle hair that kinked in odd directions. She does not think that any other members of her family including her sister's husband have had this disorder. If this couple had a son, what is the most likely chance that he would have the same disorder that affected the patient's nephew?

A pathologist performed an autopsy on an 18-month-old infant boy who died of pneumonia. Clinical notes revealed the infant had repeated respiratory infections that started after he was weaned off of breast-milk. Laboratory investigation revealed hypogammaglobulinemia and an absence of B-cells. T-cell levels were normal. Histological evaluation of an axillary lymph node revealed an absence of germinal centers. Which of the following is the mode of inheritance of the disorder that afflicted this infant?

A 36-year-old G4P0A3 woman presents at the prenatal diagnostic center at 18 weeks of gestation for the scheduled fetal anomaly scan. The patient's past medical history reveals spontaneous abortions. She reports that her 1st, 2nd, and 3rd pregnancy losses occurred at 8, 10, and 12 weeks of gestation, respectively. Ultrasonography indicates a female fetus with cystic hygroma (measuring 4 cm x 5 cm in size) and fetal hydrops. Which of the following karyotypes does her fetus most likely carry?

A 5-year-old boy is brought to a pediatrician by his parents for evaluation of learning difficulties in school. He has short stature, a flat face, low-set ears, a large tongue, and a single line on the palm. He was born to his parents after 20 years of marriage. You ordered karyotyping which will likely reveal which of the following?

A 6-year-old girl comes with her parents to the physician's office to initiate care with a new physician. The patient was recently adopted and her parents do not know her birth history; however, she has had some issues with fatigue. They were told by the adoption agency that the patient has required blood transfusions for "low blood count" in the past but they are not aware of the reason for these transfusions. Her temperature is 37.8°C (99.8°F), blood pressure is 110/84 mmHg, and pulse is 95/min. Physical examination is notable for conjunctival pallor, pale skin, and mild splenomegaly. A complete blood count is taken in the office with the following results: Hemoglobin: 6.8 g/dL Leukocyte count: 5,000/mm^3 Platelet count: 190,000/mm^3 Peripheral smear shows spherocytes and further analysis reveals rigid red blood cells. The most likely cause of this patient's symptoms has which of the following modes of inheritance?

A 28-year-old man presents for severe abdominal pain and is diagnosed with appendicitis. He is taken for emergent appendectomy. During the procedure, the patient has massive and persistent bleeding requiring a blood transfusion. The preoperative laboratory studies showed a normal bleeding time, normal prothrombin time (PT), an INR of 1.0, and a normal platelet count. Postoperatively, when the patient is told about the complications during the surgery, he recalls that he forgot to mention that he has a family history of an unknown bleeding disorder. The postoperative laboratory tests reveal a prolonged partial thromboplastin time (PTT). Which of the following is the most likely diagnosis in this patient?

Q10

A 19-year-old male from rural West Virginia presents to his family medicine doctor to discuss why he is having trouble getting his wife pregnant. On exam, he is 6 feet 2 inches with a frail frame and broad hips for a male his size. He is noted to have mild gynecomastia, no facial hair, and small, underdeveloped testes. He claims that although he has a lower libido than most of his friends, he does have unprotected sex with his wife. His past medical history is notable for developmental delay and difficulties in school. What is the most likely chromosomal abnormality in this patient?

Genetic disorders US Medical PG Practice Questions and MCQs

Question 1: A genetic counselor sees a family for the first time for genetic assessment. The 24-year-old businessman and his 19-year-old sister are concerned about having a mutant allele and have decided to get tested. Their grandfather and great aunt both have Huntington’s disease which became apparent when they turned 52. Their father who is 47 years old appears healthy. The geneticist discusses both the benefits and risks of getting tested and orders some tests. Which of the following tests would best provide evidence for whether the siblings are carriers or not?

A. Gel electrophoresis
B. Restriction enzyme digestion products
C. Polymerase chain reaction (Correct Answer)
D. Pyrosequencing
E. DNA isolation and purification

Explanation: ***Polymerase chain reaction*** - **PCR is the essential first step** for detecting Huntington's disease carrier status by **amplifying the CAG trinucleotide repeat region** in the *HTT* gene. - After PCR amplification, **fragment analysis** (capillary electrophoresis or gel electrophoresis) is used to determine the exact number of CAG repeats, which distinguishes carriers (≥36 repeats) from non-carriers (<27 repeats). - Among the options listed, **PCR is the critical enabling technology** without which carrier testing cannot proceed. - The complete diagnostic test is called "CAG repeat analysis" or "trinucleotide repeat analysis," which uses PCR as its foundation. *Gel electrophoresis* - **Gel electrophoresis** can be used to visualize the size of PCR-amplified DNA fragments and may help distinguish expanded repeats from normal-sized alleles. - However, modern laboratories typically use **capillary electrophoresis** (automated fragment analysis) for more precise repeat counting. - Gel electrophoresis alone, without prior PCR amplification, cannot detect the CAG repeat expansion. *Restriction enzyme digestion products* - Huntington's disease is caused by a **CAG trinucleotide repeat expansion**, not a point mutation that creates or abolishes restriction enzyme sites. - **Restriction fragment length polymorphism (RFLP)** analysis is not the primary method for detecting dynamic repeat expansions. - This approach was historically used for linkage analysis before direct repeat testing became available. *Pyrosequencing* - **Pyrosequencing** is designed for **sequencing short DNA stretches** and detecting single nucleotide polymorphisms (SNPs). - It is **not suitable for quantifying long trinucleotide repeat expansions** like those in Huntington's disease, where repeat numbers can range from 10 to over 100. - **Fragment analysis** is the standard method for measuring repeat length, not sequencing. *DNA isolation and purification* - **DNA isolation** is a necessary preliminary step for any genetic testing but provides no diagnostic information by itself. - It simply extracts genomic DNA from blood or tissue samples, which must then be analyzed using specific molecular techniques like PCR and fragment analysis.

Question 2: A 12-year-old boy develops muscle weakness and pain, vomiting, seizures, and severe headache. Additionally, he presents with hemiparesis on one side of the body. A muscle biopsy shows 'ragged red fibers'. What is true about the mode of inheritance of the disease described?

A. Skips generations
B. Commonly more severe in males
C. It can be transmitted through both parents.
D. It is transmitted only through the mother. (Correct Answer)
E. Mothers transmit to 50% of daughters and sons

Explanation: ***It is transmitted only through the mother.*** - The constellation of symptoms (muscle weakness, pain, vomiting, seizures, severe headache, hemiparesis) and the presence of **"ragged red fibers"** on muscle biopsy are classic findings in **Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome**. - **Mitochondrial disorders**, including MELAS, are inherited exclusively from the mother because ova contribute mitochondria to the zygote, while sperm contribute virtually none. *Mothers transmit to 50% of daughters and son* - This statement describes the inheritance pattern of an **X-linked recessive** or, in some cases, **autosomal dominant** trait with incomplete penetrance, which is not characteristic of mitochondrial inheritance. - In mitochondrial inheritance, all offspring (100%) of an affected mother will inherit the mitochondrial DNA, though the penetrance and expressivity can vary. *Skips generations* - "Skipping generations" is a hallmark of **recessive inheritance patterns**, where affected individuals may have unaffected parents who are carriers. - This is not typical for **mitochondrial inheritance**, where the disease is usually present in every generation through the maternal line. *Commonly more severe in males* - While some genetic conditions show sex-specific severity, such as X-linked disorders that are often more severe in males due to having only one X chromosome, this is not a general rule for **mitochondrial diseases**. - The severity of mitochondrial disorders is often related to the **proportion of mutated mitochondrial DNA (heteroplasmy)**, which can vary between sexes and tissues. *It can be transmitted through both parents.* - This statement generally describes **autosomal recessive** or **autosomal dominant** inheritance patterns, where genetic material from both parents contributes to the child's genotype. - **Mitochondrial inheritance** is exclusively maternal, as only the mother contributes mitochondria to the offspring.

Question 3: A 32-year-old woman comes to the physician for genetic consultation. She has a history of recurrent generalized seizures, diffuse muscular weakness, and multiple episodes of transient left-sided paresis. She has been hospitalized several times for severe lactic acidosis requiring intravenous fluid hydration. Her 10-year-old daughter also has seizures and muscle weakness. Her 7-year-old son has occasional muscle weakness and headaches but has never had a seizure. Pathologic examination of a biopsy specimen from the woman's soleus muscle shows ragged-appearing muscle fibers. Genetic analysis of the patient's son is most likely to show which of the following?

A. Mutation in DNA repair gene
B. Genetically distinct cell lines
C. Silenced paternal gene copy
D. Heterogenous mitochondrial DNA (Correct Answer)
E. Altered allele on the X chromosome

Explanation: ***Heterogenous mitochondrial DNA*** - This scenario describes **Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)**, a mitochondrial disorder characterized by diverse symptoms. - Due to **maternal inheritance**, all children of an affected mother inherit mitochondrial DNA, but the **heteroplasmy** (mix of normal and mutated mitochondrial DNA) can vary, leading to different disease severities, as seen in the son's milder symptoms. *Mutation in DNA repair gene* - Mutations in DNA repair genes are associated with conditions like **xeroderma pigmentosum** and **hereditary nonpolyposis colorectal cancer**. - These conditions typically present with **increased cancer risk** and hypersensitivity to DNA-damaging agents, not the neurological and muscular symptoms described. *Genetically distinct cell lines* - This refers to **mosaicism**, where an individual has two or more genetically different sets of cells. - While mosaicism can cause variable disease presentation, the inheritance pattern and specific symptoms (lactic acidosis, "ragged red fibers") are highly indicative of a mitochondrial disorder. *Silenced paternal gene copy* - This describes **genomic imprinting**, where one parent's gene copy is methylated and silenced. - Conditions like **Prader-Willi** and **Angelman syndromes** arise from defects in imprinting, but their clinical features differ significantly from those presented here. *Altered allele on the X chromosome* - This refers to **X-linked inheritance**, seen in disorders like **Duchenne muscular dystrophy** or **fragile X syndrome**. - X-linked disorders have distinct inheritance patterns (e.g., affected males, carrier females) and different clinical presentations compared to MELAS, which is maternally inherited.

Question 4: A 23-year-old woman and her husband come to a genetic counselor because she is concerned about the chance of having an inherited defect if they had a child. Family history reveals no significant family history in her husband; however, her sister had a son who has seizures, failure to thrive, and neurodegeneration. She does not remember the name of the disease but remembers that her nephew had sparse, brittle hair that kinked in odd directions. She does not think that any other members of her family including her sister's husband have had this disorder. If this couple had a son, what is the most likely chance that he would have the same disorder that affected the patient's nephew?

A. 100%
B. 12.5%
C. 25% (Correct Answer)
D. 50%
E. Close to 0%

Explanation: ***25%*** - The nephew's symptoms of **seizures, failure to thrive, neurodegeneration**, and **sparse, brittle, kinky hair** are highly indicative of **Menkes disease**, an **X-linked recessive** disorder. - Since the patient's sister had an affected son, the sister is an **obligate carrier** of the mutation. - The patient and her sister share the same parents, so their mother must be a carrier (or have the mutation). - The patient herself has a **50% chance of being a carrier**. - **If the patient is a carrier**, each son has a **50% chance** of being affected. - **Overall probability**: 0.5 (chance patient is carrier) × 0.5 (chance son inherits mutation) = **0.25 = 25%**. *Close to 0%* - This would only be correct if the patient had no chance of being a carrier, which is not the case given her family history. - Her sister's affected son confirms the mutation is present in the maternal lineage. *100%* - This would only occur if the patient were definitely a carrier AND all male offspring inherited the mutation, or if the disorder were autosomal dominant with complete penetrance. - For **X-linked recessive** disorders, even carrier mothers only pass the mutation to 50% of sons on average. *12.5%* - This percentage might represent additional generational steps or compound probabilities not relevant to this direct parent-child scenario. - The correct calculation for this scenario is 50% × 50% = 25%. *50%* - This would be correct if we knew with certainty that the patient is a carrier. - However, since we only know her sister is a carrier, the patient has a 50% chance of being a carrier herself, making the overall risk 25%. - This is a common error in genetic counseling calculations—forgetting to account for the uncertain carrier status of the at-risk individual.

Question 5: A pathologist performed an autopsy on an 18-month-old infant boy who died of pneumonia. Clinical notes revealed the infant had repeated respiratory infections that started after he was weaned off of breast-milk. Laboratory investigation revealed hypogammaglobulinemia and an absence of B-cells. T-cell levels were normal. Histological evaluation of an axillary lymph node revealed an absence of germinal centers. Which of the following is the mode of inheritance of the disorder that afflicted this infant?

A. Autosomal dominant
B. Mitochondrial inheritance
C. Autosomal recessive
D. X-linked recessive (Correct Answer)
E. X-linked dominant

Explanation: ***X-linked recessive*** - This presentation, including **recurrent respiratory infections** after weaning, **hypogammaglobulinemia**, absence of B-cells, normal T-cells, and absent germinal centers, is classic for **X-linked agammaglobulinemia (XLA)**, also known as Bruton's agammaglobulinemia. - XLA is caused by a mutation in the **Bruton's tyrosine kinase (BTK)** gene on the X chromosome, leading to a block in B-cell maturation. *Autosomal dominant* - Autosomal dominant disorders typically affect males and females equally, and often a parent is also affected; this pattern is not consistent with the described **X-linked inheritance** characteristic of XLA. - While some immune deficiencies can be autosomal dominant, the specific constellation of symptoms strongly points away from this mode of inheritance for this particular disease. *Mitochondrial inheritance* - Mitochondrial disorders are transmitted maternally, affecting all offspring of an affected mother, which is not characteristic of the described **immunodeficiency's inheritance pattern**. - These disorders typically manifest with **neurological** or **muscular dysfunction**, which are not the primary symptoms here. *Autosomal recessive* - Autosomal recessive disorders affect individuals who inherit two copies of the mutated gene (one from each parent), and often there's a family history of affected siblings but not typically affected parents. - While some combined immunodeficiencies can be autosomal recessive, the specific B-cell maturation defect described here for XLA is **X-linked recessive**. *X-linked dominant* - X-linked dominant disorders affect both males and females, with an affected father passing the trait to all his daughters but none of his sons, and an affected mother having a 50% chance of passing it to each child regardless of sex. - This pattern of inheritance is **not consistent** with the manifestation and prevalence of XLA, which primarily affects males due to its recessive nature.

Question 6: A 36-year-old G4P0A3 woman presents at the prenatal diagnostic center at 18 weeks of gestation for the scheduled fetal anomaly scan. The patient's past medical history reveals spontaneous abortions. She reports that her 1st, 2nd, and 3rd pregnancy losses occurred at 8, 10, and 12 weeks of gestation, respectively. Ultrasonography indicates a female fetus with cystic hygroma (measuring 4 cm x 5 cm in size) and fetal hydrops. Which of the following karyotypes does her fetus most likely carry?

A. 45 X0 (Correct Answer)
B. Monosomy 18
C. Trisomy 13
D. Trisomy 21
E. Monosomy 13

Explanation: ***45 X0*** - The presence of **cystic hygroma** and **fetal hydrops** strongly suggests **Turner syndrome (45, X0)**, as these are classic sonographic findings. - The history of **recurrent early pregnancy losses** is also consistent with chromosomal aneuploidies, with 45, X0 being a common cause of such losses. *Monosomy 18* - **Monosomy 18** is a very rare and usually lethal chromosomal abnormality, typically resulting in **early miscarriage**. - Its clinical presentation, if live-born, is distinct and does not primarily feature **cystic hygroma** or **hydrops** as the main diagnostic clues. *Trisomy 13* - **Trisomy 13 (Patau syndrome)** is associated with severe malformations, including **cleft lip/palate**, **polydactyly**, and **holoprosencephaly**. - While it can cause fetal hydrops and other structural anomalies, **cystic hygroma** is not its most characteristic or common sonographic marker in the way it is for Turner syndrome. *Trisomy 21* - **Trisomy 21 (Down syndrome)** is characterized by **nuchal translucency** and **cardiac defects**, but **cystic hygroma** and **hydrops** are less common and less severe than in Turner syndrome. - The constellation of findings in this case points more strongly to Turner syndrome. *Monosomy 13* - **Monosomy 13** is an extremely rare and usually **lethal** chromosomal anomaly, often leading to early spontaneous abortion. - It would typically result in more severe generalized developmental defects rather than the specific combination of **cystic hygroma** and **hydrops** seen here.

Question 7: A 5-year-old boy is brought to a pediatrician by his parents for evaluation of learning difficulties in school. He has short stature, a flat face, low-set ears, a large tongue, and a single line on the palm. He was born to his parents after 20 years of marriage. You ordered karyotyping which will likely reveal which of the following?

A. 47, XXX
B. 47, XY, +18
C. 47, XXY
D. 45, XO
E. 47, XY, +21 (Correct Answer)

Explanation: ***47, XY, +21*** - The patient's presentation with **short stature**, a **flat face**, **low-set ears**, a **large tongue**, a **single palmar crease (Simian crease)**, and **learning difficulties** are classic diagnostic features of **Down syndrome**. - **Down syndrome** is caused by the presence of an extra copy of chromosome 21, leading to a karyotype of **47, XY, +21** (if male) or 47, XX, +21 (if female). The mention of the parents' age (born after 20 years of marriage implies an older maternal age) is a significant risk factor for Down syndrome. *47, XXX* - This karyotype describes **Triple X syndrome**, which affects females. Individuals usually present with normal appearance, learning difficulties, and often do not have distinct physical features like those described in the case. - The patient is a 5-year-old boy, immediately ruling out Triple X syndrome. *47, XY, +18* - This karyotype indicates **Edwards syndrome (Trisomy 18)**. While it presents with developmental delay and distinctive physical features, these typically include a **rocker-bottom feet**, **clenched hands**, and other severe abnormalities often leading to early demise. - The specific features described in the patient, such as a **flat face** and **single palmar crease**, are not characteristic of Edwards syndrome. *47, XXY* - This karyotype describes **Klinefelter syndrome**, which affects males. This condition is characterized by **tall stature**, **hypogonadism**, and often **learning difficulties**, but the patient's features like **short stature**, **flat face**, and **single palmar crease** are not consistent with Klinefelter syndrome. - The phenotype of Klinefelter syndrome becomes more evident in adolescence and adulthood. *45, XO* - This karyotype describes **Turner syndrome**, which affects females. Features include **short stature**, **webbed neck**, and **gonadal dysgenesis**. - The patient is a 5-year-old boy, which rules out Turner syndrome.

Question 8: A 6-year-old girl comes with her parents to the physician's office to initiate care with a new physician. The patient was recently adopted and her parents do not know her birth history; however, she has had some issues with fatigue. They were told by the adoption agency that the patient has required blood transfusions for "low blood count" in the past but they are not aware of the reason for these transfusions. Her temperature is 37.8°C (99.8°F), blood pressure is 110/84 mmHg, and pulse is 95/min. Physical examination is notable for conjunctival pallor, pale skin, and mild splenomegaly. A complete blood count is taken in the office with the following results: Hemoglobin: 6.8 g/dL Leukocyte count: 5,000/mm^3 Platelet count: 190,000/mm^3 Peripheral smear shows spherocytes and further analysis reveals rigid red blood cells. The most likely cause of this patient's symptoms has which of the following modes of inheritance?

A. Autosomal recessive
B. Autosomal dominant (Correct Answer)
C. Mitochondrial inheritance
D. X-linked dominant
E. X-linked recessive

Explanation: ***Autosomal dominant*** - The clinical picture of severe **anemia** requiring transfusions, **splenomegaly**, and peripheral smear findings of **spherocytes** and rigid red blood cells is highly suggestive of **hereditary spherocytosis**. - **Hereditary spherocytosis** is caused by defects in red blood cell membrane proteins (e.g., spectrin, ankyrin), and the **most common mode of inheritance** for this condition is **autosomal dominant** (approximately 75% of cases). *Autosomal recessive* - While approximately **25%** of hereditary spherocytosis cases result from **autosomal recessive inheritance** or de novo mutations, the majority (~75%) follow an autosomal dominant pattern. - The severity of presentation alone does not distinguish between inheritance patterns; both can present with severe anemia requiring transfusions. - Other common red blood cell disorders, such as **sickle cell anemia** and **beta-thalassemia**, are autosomal recessive, but their characteristic findings (e.g., sickle cells, target cells) are not described here. *Mitochondrial inheritance* - **Mitochondrial disorders** primarily affect organs with high energy demands (e.g., muscles, brain) and do not typically cause isolated hemolytic anemia with spherocytes. - This mode of inheritance involves genes located in the **mitochondrial DNA** and is passed down exclusively from the mother. *X-linked dominant* - **X-linked dominant** disorders affect both males and females (though often more severely in males) and do not fit the typical presentation or known genetic basis of hereditary spherocytosis. - Examples include **Rett syndrome** and **incontinentia pigmenti**. *X-linked recessive* - **X-linked recessive** disorders, such as **G6PD deficiency** or **hemophilia**, are more common in males and have distinct clinical and laboratory features that do not match the patient's presentation of hereditary spherocytosis. - While **G6PD deficiency** can cause hemolytic anemia, it is typically triggered by oxidative stress and does not primarily involve spherocytes or chronic splenomegaly in the same manner.

Question 9: A 28-year-old man presents for severe abdominal pain and is diagnosed with appendicitis. He is taken for emergent appendectomy. During the procedure, the patient has massive and persistent bleeding requiring a blood transfusion. The preoperative laboratory studies showed a normal bleeding time, normal prothrombin time (PT), an INR of 1.0, and a normal platelet count. Postoperatively, when the patient is told about the complications during the surgery, he recalls that he forgot to mention that he has a family history of an unknown bleeding disorder. The postoperative laboratory tests reveal a prolonged partial thromboplastin time (PTT). Which of the following is the most likely diagnosis in this patient?

A. von Willebrand disease
B. Bernard-Soulier syndrome
C. Thrombotic thrombocytopenic purpura
D. Hemophilia A (Correct Answer)
E. Glanzmann thrombasthenia

Explanation: ***Hemophilia A*** - The patient's presentation with **severe, persistent bleeding** during surgery despite normal preoperative coagulation studies (PT, INR, platelet count) and a subsequent **prolonged PTT** strongly indicates a **factor deficiency in the intrinsic pathway**. - **Hemophilia A**, an X-linked recessive disorder, is caused by a deficiency of **Factor VIII**, leading to a prolonged PTT and deep tissue bleeding, which fits the clinical picture and family history. *von Willebrand disease* - This condition typically presents with **mucocutaneous bleeding** (e.g., nosebleeds, menorrhagia) and can have a prolonged bleeding time, but the primary defect is in **platelet adhesion**, not usually massive operative bleeding with normal platelet count. - While **von Willebrand factor (vWF)** carries Factor VIII, a primary deficiency of vWF would affect factor VIII levels but the presentation and normal bleeding time here make it less likely than direct factor VIII deficiency. *Bernard-Soulier syndrome* - This is a **platelet disorder** characterized by defective **glycoprotein Ib/IX/V complex**, leading to impaired platelet adhesion and often **thrombocytopenia** with unusually large platelets. - The patient had a **normal platelet count** and a subsequent prolonged PTT, which points away from a primary platelet adhesion defect. *Thrombotic thrombocytopenic purpura* - This is a microangiopathic hemolytic anemia characterized by a **pentad of symptoms**: fever, neurologic symptoms, renal dysfunction, thrombocytopenia, and microangiopathic hemolytic anemia. - It involves widespread **thrombosis** and **low platelet count**, which does not align with the patient's presentation of massive bleeding with normal platelet counts. *Glanzmann thrombasthenia* - This is a rare **platelet aggregation disorder** caused by a defect in **glycoprotein IIb/IIIa**, leading to impaired fibrinogen binding and platelet aggregation. - While it causes severe bleeding, it would be associated with a **prolonged bleeding time** and normal PTT, which contradicts the patient's normal bleeding time and prolonged PTT.

Question 10: A 19-year-old male from rural West Virginia presents to his family medicine doctor to discuss why he is having trouble getting his wife pregnant. On exam, he is 6 feet 2 inches with a frail frame and broad hips for a male his size. He is noted to have mild gynecomastia, no facial hair, and small, underdeveloped testes. He claims that although he has a lower libido than most of his friends, he does have unprotected sex with his wife. His past medical history is notable for developmental delay and difficulties in school. What is the most likely chromosomal abnormality in this patient?

A. Trisomy 13
B. 45: XO
C. Trisomy 21
D. 47: XYY
E. 47: XXY (Correct Answer)

Explanation: ***47: XXY*** - The patient's presentation with **infertility**, small testes, **gynecomastia**, eunuchoid body habitus (tall, frail frame, broad hips), lack of facial hair, and **developmental delay** are classic features of **Klinefelter syndrome (47, XXY)**. - This chromosomal abnormality leads to primary **hypogonadism** due to the presence of an extra X chromosome in males. *Trisomy 13* - Trisomy 13, or **Patau syndrome**, is characterized by severe developmental anomalies, including **cleft lip and palate**, polydactyly, and severe neurological defects. - Infants with Trisomy 13 rarely survive beyond the first year and do not present with the described signs of hypogonadism or gynecomastia in adolescence. *45: XO* - **45, XO** or **Turner syndrome** affects females and is characterized by **short stature**, primary amenorrhea, webbed neck, and **gonadal dysgenesis (streak gonads)**. - This karyotype is incompatible with a male phenotype and the symptoms described. *Trisomy 21* - Trisomy 21, or **Down syndrome**, is associated with distinct facial features, intellectual disability, and congenital heart defects. - While individuals with Down syndrome may have fertility issues, they do not typically present with the specific combination of **gynecomastia**, eunuchoid habitus, and **small testes** seen in this patient. *47: XYY* - **47, XYY syndrome** is associated with increased height and potentially some learning difficulties, but typically does not cause the significant **hypogonadism**, **gynecomastia**, or **small testes** seen in this patient. - Men with 47, XYY usually have normal sexual development and fertility, though some may experience learning disabilities or behavioral problems.

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