An adult tall male presents with a long arm span, pectus excavatum, and cardiac abnormalities. What is the most likely defective protein?
Q2
Which disease will show the mode of inheritance depicted in this pedigree?
Q3
A 12-year-old girl is brought to an oncologist, as she was recently diagnosed with a rare form of cancer. Cytogenetic studies reveal that the tumor is responsive to vinblastine, which is a cell-cycle specific anticancer agent. It acts on the M phase of the cell cycle and inhibits the growth of cells. Which of the following statements best describes the regulation of the cell cycle?
Q4
A 4-year-old male presents with a 1-year history of swaying while walking and recent episodes of tripping when ambulating. He has trouble trying to sit and get up from chairs, as well as walking up the stairs to his bedroom. On physical exam, the pediatrician notices nystagmus, absent deep tendon reflexes, significant loss of vibratory and proprioceptive sensation in his extremities, pes cavus, and slight kyphoscoliosis. A blood sample is sent for DNA sequencing and the results show a significant expansion of the trinucleotide GAA on chromosome 9. Which of the following diseases displays a similar mode of inheritance as the disease affecting this patient?
Q5
A 1-year-old child who was born outside of the United States is brought to a pediatrician for the first time because she is not gaining weight. Upon questioning, the pediatrician learns that the child has had frequent pulmonary infections since birth, and on exam the pediatrician appreciates several nasal polyps. Genetic testing is subsequently ordered to confirm the suspected diagnosis. Testing is most likely to show deletion of which of the following amino acids from the protein involved in this child's condition?
Q6
A 19-year-old man presents to the office for a routine physical exam and a meningitis vaccination prior to attending college on a basketball scholarship. Also present at the appointment is his father who appears to be in his mid-sixties and is much shorter. The patient’s pulse is 70/min, respirations are 18/min, temperature is 37.0°C (98.6°F), and blood pressure is 120/80 mm Hg. He is 183 cm (6 ft 0 in) tall and weighs 79.4 kg (175 lb). His heart rate is regular with a mild diastolic murmur (II/VI) over the aortic valve and his lungs are clear to auscultation bilaterally. A scoliosis test shows mild deviation of his thoracic spine. A skin examination shows numerous red-to-white linear markings on the skin around his lower back. His fingers are long. Which of the following genes does this patient most likely have a mutation of?
Q7
An 11-year-old boy is brought to the physician for the evaluation of frequent falling. His mother reports that the patient has had increased difficulty walking over the last few months and has refused to eat solid foods for the past 2 weeks. He has met all developmental milestones. The patient has had multiple ear infections since birth. His temperature is 37°C (98.6°F), pulse is 90/min, and blood pressure is 120/80 mm Hg. Examination shows foot inversion with hammertoes bilaterally. His gait is wide-based with irregular and uneven steps. Laboratory studies show a serum glucose concentration of 300 mg/dL. Further evaluation of this patient is most likely to show which of the following findings?
Q8
A 9-year-old boy is admitted to the hospital for placement of halo gravitational traction in order to treat his previously observed kyphoscoliosis. Specifically, he has a previously diagnosed curve that has gotten worse over time and now threatens to compromise his thoracic cavity. His past medical history is significant for short stature, and he has consistently been below the 5th percentile for height since birth. On physical exam, he is found to have macrocephaly with frontal bossing, short arms and legs with disproportionate shortening of the proximal segments, and lumbar lordosis. Which of the following proteins are most likely mutated in this patient?
Q9
A mother brings her son to the pediatrician because she is concerned about his health. She states that throughout her child's life he has demonstrated aggressive behavior. However, he has recently begun biting himself causing injury and bleeding. The patient has a past medical history of mental retardation and episodes of severe joint pain. His temperature is 99.5°F (37.5°C), blood pressure is 87/48 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam reveals a child attempting to bite his arms. Which of the following is the inheritance pattern of the disease with which this patient presents?
Q10
A 40-year-old woman brings her 2-day-old infant to the pediatrician’s office for a routine checkup. She tells the pediatrician that her baby vomits a greenish-yellow fluid after every feeding session. She has not been very successful in feeding him due to this problem. She also says that her baby has not passed stool since they left the hospital. On examination, the pediatrician observes that the baby has a flat facial profile and small eyes. The epicanthal folds are prominent and the palms have a single transverse crease. His abdomen is distended with high-pitched bowel sounds. The pediatrician orders an abdominal radiograph, the film is shown in the picture. Which of the following best explains the physical and clinical features exhibited by this infant?
Molecular Genetics US Medical PG Practice Questions and MCQs
Question 1: An adult tall male presents with a long arm span, pectus excavatum, and cardiac abnormalities. What is the most likely defective protein?
A. Fibrillin (Correct Answer)
B. Elastin
C. Collagen
D. Myosin
E. Laminin
Explanation: ***Fibrillin***
- The constellation of **tall stature**, **long arm span**, **pectus excavatum**, and **cardiac abnormalities** (e.g., aortic dissection or mitral valve prolapse) is classic for **Marfan syndrome**.
- Marfan syndrome is caused by a defect in the *FBN1* gene, which codes for **fibrillin-1**, a glycoprotein essential for the formation of elastic fibers in connective tissue.
*Elastin*
- Defects in **elastin** are associated with conditions like **supravalvular aortic stenosis** (due to **Williams syndrome**) or cutis laxa, which have different phenotypic presentations.
- While both elastin and fibrillin are components of elastic fibers, the specific features of Marfan syndrome point to fibrillin as the primary defect.
*Collagen*
- Defects in **collagen** (especially type I, III, or V) are associated with conditions such as **osteogenesis imperfecta** (brittle bones) or **Ehlers-Danlos syndrome** (hypermobility, skin hyperextensibility).
- These conditions typically present with different clinical manifestations, lacking the specific combination of features seen in this patient.
*Myosin*
- **Myosin** is a fibrous protein primarily involved in **muscle contraction** and is not directly implicated in widespread connective tissue disorders affecting skeletal and cardiovascular systems in this manner.
- Defects in myosin are more commonly associated with various forms of **cardiomyopathy** or skeletal muscle myopathies, not Marfan-like features.
*Laminin*
- **Laminin** is a major component of the **basement membrane** and plays a role in cell adhesion, migration, and tissue architecture.
- Laminin defects are associated with certain forms of **muscular dystrophy** (e.g., congenital muscular dystrophy) and **epidermolysis bullosa**, not the specific skeletal and cardiovascular features of Marfan syndrome.
Question 2: Which disease will show the mode of inheritance depicted in this pedigree?
A. Achondroplasia (Correct Answer)
B. Prader-Willi syndrome
C. Wilson disease
D. Wiskott-Aldrich syndrome
E. Hemophilia A
Explanation: ***Achondroplasia***
- This pedigree shows an **autosomal dominant** inheritance pattern, characterized by affected individuals in every generation, affected offspring with at least one affected parent, and direct transmission from father to son (which **rules out X-linked**). Achondroplasia is an autosomal dominant disorder.
- The presence of **affected individuals (shaded squares/circles)** in each successive generation and the 1:1 ratio of affected to unaffected offspring from affected parents mating with unaffected individuals supports autosomal dominant inheritance.
*Prader-Willi syndrome*
- This syndrome is caused by **genomic imprinting** or a chromosomal deletion on chromosome 15, typically inherited from the father. It does not follow a simple Mendelian dominant or recessive inheritance pattern.
- While it has a genetic basis, its inheritance pattern is **complex** and involves specific parental origin of the genetic defect, unlike the clear autosomal dominant pattern shown.
*Wilson disease*
- Wilson disease is an **autosomal recessive** disorder, meaning affected individuals inherit two copies of the mutated gene (one from each parent).
- This pedigree does not show skipped generations or unaffected parents having affected offspring, which would be characteristic of **autosomal recessive** inheritance.
*Wiskott-Aldrich syndrome*
- Wiskott-Aldrich syndrome is an **X-linked recessive** disorder. This means it primarily affects males, and affected fathers cannot pass the trait to their sons.
- The pedigree shows **affected females** (shaded circles) and **father-to-son transmission** (e.g., father in second generation to son in third generation, assuming the leftmost branch is the paternal line), which rules out X-linked inheritance.
*Hemophilia A*
- Hemophilia A is an **X-linked recessive** disorder affecting the Factor VIII gene, predominantly affecting males.
- Similar to Wiskott-Aldrich syndrome, the presence of **father-to-son transmission** in the pedigree rules out X-linked inheritance patterns, as affected fathers cannot pass X-linked traits to their sons.
Question 3: A 12-year-old girl is brought to an oncologist, as she was recently diagnosed with a rare form of cancer. Cytogenetic studies reveal that the tumor is responsive to vinblastine, which is a cell-cycle specific anticancer agent. It acts on the M phase of the cell cycle and inhibits the growth of cells. Which of the following statements best describes the regulation of the cell cycle?
A. Inhibitors of DNA synthesis act in the M phase of the cell cycle.
B. The G0 phase is the checkpoint before G1.
C. Cyclin-dependent activation of CDK1 (CDC2) takes place upon the entry of a cell into M phase of the cell cycle. (Correct Answer)
D. EGF from a blood clot stimulates the growth and proliferation of cells in the healing process.
E. Replication of the genome occurs in the M phase of the cell cycle.
Explanation: ***Cyclin-dependent activation of CDK1 (CDC2) takes place upon the entry of a cell into M phase of the cell cycle.***
- The **M-phase promoting factor (MPF)**, composed of **CDK1 (CDC2)** and **cyclin B**, is activated at the G2/M transition, driving the cell into mitosis.
- Activation of CDK1 by **cyclin B binding** and subsequent dephosphorylation of threonine 161 is crucial for initiation of mitosis.
*Inhibitors of DNA synthesis act in the M phase of the cell cycle.*
- **Inhibitors of DNA synthesis**, such as **hydroxyurea** and **methotrexate**, primarily act during the **S phase** of the cell cycle, when DNA replication occurs.
- The M phase is characterized by **mitosis** (nuclear division) and **cytokinesis** (cytoplasmic division), not DNA synthesis.
*The G0 phase is the checkpoint before G1.*
- The **G0 phase** is a **resting state** where cells exit the cell cycle and cease to divide, not a checkpoint before G1.
- The main checkpoint before G1 is typically referred to as the **restriction point** or **G1 checkpoint**, which determines if a cell will commit to division.
*EGF from a blood clot stimulates the growth and proliferation of cells in the healing process.*
- While **EGF (Epidermal Growth Factor)** does stimulate cell growth and proliferation in healing, it is not primarily associated with blood clots.
- **Platelets** in blood clots release growth factors like **PDGF (Platelet-Derived Growth Factor)** and **TGF-β (Transforming Growth Factor-beta)**, which are critical for wound healing.
*Replication of the genome occurs in the M phase of the cell cycle.*
- **Replication of the genome** (DNA synthesis) occurs during the **S phase** (synthesis phase) of the cell cycle.
- The **M phase** is dedicated to **mitosis** (separation of duplicated chromosomes) and **cytokinesis**, where the cell divides into two daughter cells.
Question 4: A 4-year-old male presents with a 1-year history of swaying while walking and recent episodes of tripping when ambulating. He has trouble trying to sit and get up from chairs, as well as walking up the stairs to his bedroom. On physical exam, the pediatrician notices nystagmus, absent deep tendon reflexes, significant loss of vibratory and proprioceptive sensation in his extremities, pes cavus, and slight kyphoscoliosis. A blood sample is sent for DNA sequencing and the results show a significant expansion of the trinucleotide GAA on chromosome 9. Which of the following diseases displays a similar mode of inheritance as the disease affecting this patient?
A. Von Gierke's disease (Correct Answer)
B. Osteogenesis imperfecta
C. Fragile X syndrome
D. Leber hereditary optic neuropathy
E. Menkes disease
Explanation: ***Von Gierke's disease***
- The patient's symptoms (ataxia, nystagmus, absent deep tendon reflexes, sensory loss, pes cavus, kyphoscoliosis) and genetic finding (GAA trinucleotide expansion on chromosome 9) are characteristic of **Friedreich's ataxia**.
- Friedreich's ataxia is inherited in an **autosomal recessive** pattern, similar to Von Gierke's disease.
*Osteogenesis imperfecta*
- This condition is primarily inherited in an **autosomal dominant** pattern, although some severe forms can be recessive.
- It is caused by defects in **collagen genes** and is characterized by brittle bones, blue sclera, and hearing loss, which are not present here.
*Fragile X syndrome*
- This is an **X-linked dominant** disorder characterized by a trinucleotide (CGG) repeat expansion on the X chromosome.
- It presents with intellectual disability, distinctive facial features, and macroorchidism, which differ from the patient's presentation.
*Leber hereditary optic neuropathy*
- This condition is inherited via **mitochondrial inheritance**, meaning it is passed down exclusively from the mother.
- It primarily causes bilateral vision loss due to optic nerve degeneration, which is not the patient's main complaint.
*Menkes disease*
- This is an **X-linked recessive** disorder, caused by a mutation in the ATP7A gene leading to copper deficiency.
- It is characterized by sparse, kinky hair, developmental delay, and neurological degeneration, a different clinical picture than described.
Question 5: A 1-year-old child who was born outside of the United States is brought to a pediatrician for the first time because she is not gaining weight. Upon questioning, the pediatrician learns that the child has had frequent pulmonary infections since birth, and on exam the pediatrician appreciates several nasal polyps. Genetic testing is subsequently ordered to confirm the suspected diagnosis. Testing is most likely to show deletion of which of the following amino acids from the protein involved in this child's condition?
A. Leucine
B. Histidine
C. Lysine
D. Valine
E. Phenylalanine (Correct Answer)
Explanation: ***Phenylalanine***
- The patient's presentation with **failure to thrive**, **recurrent pulmonary infections**, and **nasal polyps** is highly suggestive of **cystic fibrosis (CF)**.
- The most common mutation leading to CF is the **delta F508 mutation**, which involves a **deletion of a phenylalanine** residue at position 508 in the **CFTR protein**.
*Leucine*
- While other rare mutations in the **CFTR gene** can involve various amino acids, **leucine deletion** is not the most common or characteristic mutation associated with the clinical picture of CF.
- This option does not represent the primary genetic defect seen in the majority of CF cases.
*Histidine*
- **Histidine deletion** is not a commonly described or significant mutation in the **CFTR gene** that would explain the overwhelming majority of cystic fibrosis cases.
- The typical genetic defect in CF involves the malformation of the CFTR protein due to phenylalanine deletion.
*Lysine*
- **Lysine deletion** is not the most prevalent type of mutation found in patients with **cystic fibrosis** nor is it associated with the characteristic presentation mentioned.
- The CFTR protein dysfunction primarily stems from the common phenylalanine deletion, affecting protein folding and function.
*Valine*
- Deletion of **valine** is not the most frequently observed mutation in the **CFTR gene** that causes cystic fibrosis.
- The classic genetic basis for CF symptoms, particularly severe ones, relates to the absence of phenylalanine.
Question 6: A 19-year-old man presents to the office for a routine physical exam and a meningitis vaccination prior to attending college on a basketball scholarship. Also present at the appointment is his father who appears to be in his mid-sixties and is much shorter. The patient’s pulse is 70/min, respirations are 18/min, temperature is 37.0°C (98.6°F), and blood pressure is 120/80 mm Hg. He is 183 cm (6 ft 0 in) tall and weighs 79.4 kg (175 lb). His heart rate is regular with a mild diastolic murmur (II/VI) over the aortic valve and his lungs are clear to auscultation bilaterally. A scoliosis test shows mild deviation of his thoracic spine. A skin examination shows numerous red-to-white linear markings on the skin around his lower back. His fingers are long. Which of the following genes does this patient most likely have a mutation of?
A. COL5A1
B. FBN1 (Correct Answer)
C. COL3A1
D. TGFBR1
E. ELN
Explanation: ***FBN1***
- The patient exhibits features consistent with **Marfan syndrome**, including tall stature, long fingers (arachnodactyly), mild scoliosis, and a diastolic murmur indicative of **aortic root dilation** or valve insufficiency. Marfan syndrome is caused by a mutation in the **FBN1 gene**, which encodes **fibrillin-1**.
- **Striae distensae** (red-to-white linear markings, or stretch marks) in a young, otherwise healthy individual are also a common cutaneous manifestation of Marfan syndrome due to connective tissue weakness.
*COL5A1*
- Mutations in **COL5A1** are associated with the **classical type of Ehlers-Danlos syndrome**, characterized by **skin hyperextensibility**, **joint hypermobility**, and **fragile tissues**, which are not the primary features described here.
- While there can be joint issues, the prominent skeletal and cardiovascular findings in this patient point away from classical Ehlers-Danlos syndrome.
*COL3A1*
- Mutations in **COL3A1** are responsible for **vascular Ehlers-Danlos syndrome**, known for **arterial rupture**, **intestinal rupture**, and **fragile, translucent skin**.
- This condition is particularly severe due to the risk of life-threatening vascular events, which are not suggested by the patient's presentation.
*TGFBR1*
- Mutations in **TGFBR1** (transforming growth factor beta receptor 1) cause **Loeys-Dietz syndrome**, another connective tissue disorder with overlapping features to Marfan syndrome, including aortic aneurysms and skeletal abnormalities.
- However, Loeys-Dietz syndrome is typically distinguished by **hypertelorism** (widely spaced eyes), **bifid uvula**, and a higher risk of **early arterial dissection**, which are not present in this patient.
*ELN*
- Mutations in the **ELN gene** encode **elastin** and are associated with **supravalvular aortic stenosis** and Williams syndrome, which presents with distinct facial features, intellectual disability, and a particular type of heart defect.
- The patient's diastolic murmur suggests aortic insufficiency or dilation, not typically supravalvular aortic stenosis, and other features of Williams syndrome are absent.
Question 7: An 11-year-old boy is brought to the physician for the evaluation of frequent falling. His mother reports that the patient has had increased difficulty walking over the last few months and has refused to eat solid foods for the past 2 weeks. He has met all developmental milestones. The patient has had multiple ear infections since birth. His temperature is 37°C (98.6°F), pulse is 90/min, and blood pressure is 120/80 mm Hg. Examination shows foot inversion with hammertoes bilaterally. His gait is wide-based with irregular and uneven steps. Laboratory studies show a serum glucose concentration of 300 mg/dL. Further evaluation of this patient is most likely to show which of the following findings?
A. Expansion of GAA trinucleotide repeats (Correct Answer)
B. Duplication of PMP22 gene
C. Mutation of type I collagen gene
D. Absence of dystrophin protein
E. Defect of ATM protein
Explanation: ***Expansion of GAA trinucleotide repeats***
- The clinical presentation of **Friedreich ataxia** includes progressive **ataxia**, **dysarthria**, **hypertrophic cardiomyopathy**, and **diabetes mellitus** (indicated by serum glucose of 300 mg/dL), consistent with the patient's symptoms.
- This condition is caused by an autosomal recessive **GAA trinucleotide repeat expansion** in the frataxin gene.
*Duplication of PMP22 gene*
- A duplication of the **PMP22 gene** is associated with **Charcot-Marie-Tooth disease type 1A**, which presents with progressive distal weakness, sensory loss, foot deformities (e.g., hammertoes, pes cavus), and a steppage gait.
- While some features overlap, the severe **ataxia** and **diabetes mellitus** seen in this patient are not characteristic of Charcot-Marie-Tooth disease.
*Mutation of type I collagen gene*
- **Type I collagen gene mutations** are characteristic of **osteogenesis imperfecta**, a connective tissue disorder causing brittle bones, blue sclerae, and hearing loss.
- The patient's symptoms of neurological decline and diabetes are not consistent with osteogenesis imperfecta.
*Absence of dystrophin protein*
- An absence of **dystrophin protein** is the hallmark of **Duchenne muscular dystrophy**, an X-linked recessive disorder causing progressive muscle weakness, Gowers' sign, and pseudohypertrophy of the calves.
- While muscle weakness would cause falling, the patient's presentation with **ataxia** and a **wide-based gait** points away from a primary muscle disorder.
*Defect of ATM protein*
- A **defect in ATM protein** is responsible for **Ataxia-telangiectasia**, an autosomal recessive disorder characterized by cerebellar ataxia, telangiectasias, immunodeficiency, and an increased risk of cancer.
- While ataxia is present, the patient's findings of **hammertoes** and **diabetes mellitus** are not typical features of Ataxia-telangiectasia.
Question 8: A 9-year-old boy is admitted to the hospital for placement of halo gravitational traction in order to treat his previously observed kyphoscoliosis. Specifically, he has a previously diagnosed curve that has gotten worse over time and now threatens to compromise his thoracic cavity. His past medical history is significant for short stature, and he has consistently been below the 5th percentile for height since birth. On physical exam, he is found to have macrocephaly with frontal bossing, short arms and legs with disproportionate shortening of the proximal segments, and lumbar lordosis. Which of the following proteins are most likely mutated in this patient?
A. FGFR3 receptor (Correct Answer)
B. Alpha-L-iduronidase
C. COL1A1 gene
D. SLC26A2 transporter
E. RUNX2 transcription factor
Explanation: ***FGFR3 receptor***
- The constellation of **short stature**, **macrocephaly with frontal bossing**, **short limbs with disproportionate shortening of proximal segments (rhizomelia)**, and **lumbar lordosis** is classic for **achondroplasia**.
- Achondroplasia is caused by an **activating mutation** in the **fibroblast growth factor receptor 3 (FGFR3)** gene, which inhibits endochondral ossification, leading to impaired bone growth.
*RUNX2 transcription factor*
- Mutations in **RUNX2** are associated with **cleidocranial dysplasia**, a disorder characterized by delayed closure of fontanelles, hypoplastic or absent clavicles, and dental abnormalities.
- While it can cause short stature and scoliosis, the specific physical features like rhizomelia and frontal bossing point away from cleidocranial dysplasia.
*Alpha-L-iduronidase*
- Deficiency of **alpha-L-iduronidase** causes **Hurler syndrome (MPS I)**, a lysosomal storage disorder.
- Patients present with coarse facial features, corneal clouding, hepatosplenomegaly, and skeletal deformities, but not typically the specific limb and head features described.
*COL1A1 gene*
- Mutations in the **COL1A1 gene** are associated with **osteogenesis imperfecta (OI)**, a disorder characterized by **brittle bones** and frequent fractures.
- While OI can cause skeletal deformities and short stature, it doesn't typically present with macrocephaly, frontal bossing, or rhizomelia in the same way as achondroplasia.
*SLC26A2 transporter*
- Mutations in the **SLC26A2 gene** are associated with **diastrophic dysplasia**, another form of dwarfism.
- While it causes short stature and skeletal issues, patients often have distinctive features like "hitchhiker's thumb," club feet, and highly mobile joints, which are not mentioned here.
Question 9: A mother brings her son to the pediatrician because she is concerned about his health. She states that throughout her child's life he has demonstrated aggressive behavior. However, he has recently begun biting himself causing injury and bleeding. The patient has a past medical history of mental retardation and episodes of severe joint pain. His temperature is 99.5°F (37.5°C), blood pressure is 87/48 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam reveals a child attempting to bite his arms. Which of the following is the inheritance pattern of the disease with which this patient presents?
A. X-linked dominant
B. Autosomal dominant
C. Autosomal recessive
D. X-linked recessive (Correct Answer)
E. Maternal
Explanation: ***X-linked recessive***
- This patient's presentation of **self-mutilation**, **mental retardation**, and **aggressive behavior** is highly suggestive of **Lesch-Nyhan syndrome**.
- Lesch-Nyhan syndrome is an **X-linked recessive disorder** caused by a defect in the gene for **hypoxanthine-guanine phosphoribosyltransferase (HGPRT)**, leading to a build-up of uric acid.
*X-linked dominant*
- X-linked dominant disorders affect both males and females, though males are often more severely affected or may have more prominent symptoms.
- Affected fathers transmit the trait to all their daughters but no sons, which is not characteristic of Lesch-Nyhan syndrome.
*Autosomal dominant*
- Autosomal dominant disorders are inherited equally by males and females, and an affected individual has a 50% chance of passing the condition to each child.
- This inheritance pattern does not fit the typical presentation of Lesch-Nyhan syndrome, which primarily affects males.
*Autosomal recessive*
- Autosomal recessive disorders typically require two copies of the mutated gene (one from each parent) for the disease to manifest, affecting males and females equally.
- While some metabolic disorders are autosomal recessive, Lesch-Nyhan syndrome's sex-linked pattern of inheritance rules out this option.
*Maternal*
- Maternal inheritance refers to conditions passed down through **mitochondrial DNA**, affecting all children of an affected mother regardless of sex.
- Affected fathers do not pass mitochondrial conditions to any of their children, since sperm contribute minimal mitochondria.
- Lesch-Nyhan syndrome is associated with a nuclear gene on the X chromosome, not mitochondrial DNA, making maternal inheritance incorrect.
Question 10: A 40-year-old woman brings her 2-day-old infant to the pediatrician’s office for a routine checkup. She tells the pediatrician that her baby vomits a greenish-yellow fluid after every feeding session. She has not been very successful in feeding him due to this problem. She also says that her baby has not passed stool since they left the hospital. On examination, the pediatrician observes that the baby has a flat facial profile and small eyes. The epicanthal folds are prominent and the palms have a single transverse crease. His abdomen is distended with high-pitched bowel sounds. The pediatrician orders an abdominal radiograph, the film is shown in the picture. Which of the following best explains the physical and clinical features exhibited by this infant?
A. Monosomy
B. Trisomy (Correct Answer)
C. Genomic imprinting
D. Anticipation
E. Locus heterogeneity
Explanation: ***Trisomy***
- The combination of **facial dysmorphism** (flat facial profile, small eyes, prominent epicanthal folds), a **single transverse palmar crease**, and **gastrointestinal obstruction** (vomiting greenish-yellow fluid, abdominal distension, high-pitched bowel sounds, failure to pass stool) strongly points to **Down syndrome (Trisomy 21)**.
- The abdominal radiograph shows a **double-bubble sign**, which is characteristic of **duodenal atresia**, a common congenital anomaly seen in infants with Trisomy 21.
*Monosomy*
- **Monosomy** refers to the absence of one chromosome from a pair. The most common human monosomy compatible with life is **Turner syndrome (Monosomy X)**, which affects females.
- Turner syndrome presents with distinct features like **short stature**, **webbed neck**, and **gonadal dysgenesis**, which are not present in this infant.
*Genomic imprinting*
- **Genomic imprinting** is an epigenetic phenomenon where certain genes are expressed in a **parent-of-origin-specific manner**. Examples include **Prader-Willi** and **Angelman syndromes**.
- These syndromes have specific clinical features (e.g., **hyperphagia** and developmental delay in Prader-Willi, severe intellectual disability and **ataxia** in Angelman) that do not match the infant's presentation.
*Anticipation*
- **Anticipation** is a phenomenon in genetics where the symptoms of a genetic disorder become **more severe** and appear at an **earlier age** in successive generations.
- This typically occurs in disorders caused by the expansion of **trinucleotide repeats**, such as **Huntington's disease** or **myotonic dystrophy**, and does not explain these congenital anomalies.
*Locus heterogeneity*
- **Locus heterogeneity** describes a condition or trait caused by mutations in **different genes** at **different chromosomal loci**.
- While many complex genetic disorders exhibit locus heterogeneity, it primarily explains **inheritance patterns** and does not directly describe the specific clinical and radiographic findings of a single patient with multiple congenital anomalies.
