A 28-year-old man presents for a pre-placement health check-up. Auscultation reveals a mid-systolic click. An echocardiogram reveals a floppy mitral valve and a dilated aortic root. An ocular examination finds a subluxated lens superior and laterally. What is the most likely genetic defect?
Q12
A 6-year-old boy with a history of multiple fractures is brought to his pediatrician by his mother, because she is concerned her child cannot hear her. On physical exam, kyphoscoliosis, poor dentition, bowing of long bones, and conductive hearing loss is noted. On genetic analysis, the patient has a COL1A1 gene mutation. The defect found in this patient is most likely associated with impaired formation of which of the following?
Q13
A 57-year-old woman comes to the physician because of increasing wrinkles on her face and sagging skin. She says that her skin used to be smooth and firm. Examination shows diffuse xerosis and mild atrophy, laxity, and fine wrinkles on the periorbital skin. Which of the following processes is most likely involved in the development of this patient's skin findings?
Epithelial/Connective tissues US Medical PG Practice Questions and MCQs
Question 11: A 28-year-old man presents for a pre-placement health check-up. Auscultation reveals a mid-systolic click. An echocardiogram reveals a floppy mitral valve and a dilated aortic root. An ocular examination finds a subluxated lens superior and laterally. What is the most likely genetic defect?
A. Fibrillin (Correct Answer)
B. Spectrin
C. Dystrophin
D. NF1 protein
E. Cystathionine synthase
Explanation: ***Fibrillin***
- The constellation of **mitral valve prolapse** (mid-systolic click, floppy mitral valve), **dilated aortic root**, and **ectopia lentis** (subluxated lens) is classic for **Marfan syndrome**.
- **Marfan syndrome** is caused by a genetic defect in **fibrillin-1 (FBN1)**, a glycoprotein crucial for forming elastic fibers in connective tissue.
*Spectrin*
- **Spectrin** is a crucial component of the **erythrocyte cytoskeleton**, maintaining the red blood cell shape.
- Defects in spectrin are associated with **hereditary spherocytosis** and **elliptocytosis**, which are red blood cell disorders, not connective tissue disorders.
*Dystrophin*
- **Dystrophin** is a protein found in **muscle cells**, providing structural integrity to muscle fibers.
- Defects in dystrophin lead to **Duchenne** and **Becker muscular dystrophies**, characterized by progressive muscle weakness.
*Cystathionine synthase*
- Deficiency of **cystathionine synthase** (also called cystathionine β-synthase) causes **homocystinuria**, a metabolic disorder that can present with some features overlapping with Marfan syndrome (e.g., lens subluxation, skeletal abnormalities).
- However, the **dilated aortic root** and the characteristic direction of lens subluxation (superior and lateral in Marfan, typically inferior and medial in homocystinuria) point away from this diagnosis.
*NF1 protein*
- **NF1 protein (neurofibromin)** is a tumor suppressor protein.
- Defects in NF1 lead to **Neurofibromatosis type 1**, characterized by **café-au-lait spots**, neurofibromas, optic gliomas, and Lisch nodules.
Question 12: A 6-year-old boy with a history of multiple fractures is brought to his pediatrician by his mother, because she is concerned her child cannot hear her. On physical exam, kyphoscoliosis, poor dentition, bowing of long bones, and conductive hearing loss is noted. On genetic analysis, the patient has a COL1A1 gene mutation. The defect found in this patient is most likely associated with impaired formation of which of the following?
A. Cartilage
B. Vitreous body of the eye
C. Lens
D. Bone (Correct Answer)
E. Sclera
Explanation: ***Bone***
- This patient has **osteogenesis imperfecta (OI)** due to a **COL1A1 gene mutation** affecting **Type I collagen** synthesis.
- **Bone** is composed primarily of Type I collagen (~90% of the organic matrix), and its formation is **severely impaired** in OI.
- The major clinical manifestations all result from defective bone formation: **multiple fractures**, **kyphoscoliosis**, **bowing of long bones**, and poor bone mineralization.
- The **conductive hearing loss** results from abnormal ossicle development and otosclerosis-like changes in the temporal bone.
- **Poor dentition** is also related to defective Type I collagen in dentin (dentinogenesis imperfecta).
*Sclera*
- While the **sclera** does contain Type I collagen and appears **blue** in OI due to thinning (allowing choroidal vessels to show through), this is a clinical sign rather than the primary site of impaired formation.
- Blue sclera is a diagnostic feature but not the main pathology - it's a visible manifestation of the collagen defect, not the primary tissue with impaired formation.
*Cartilage*
- **Cartilage** is primarily composed of **Type II collagen**, not Type I collagen.
- Defects in Type II collagen cause **chondrodysplasias**, which present differently from this clinical picture.
*Vitreous body of the eye*
- The **vitreous body** is primarily composed of **Type II collagen** and hyaluronic acid.
- It is not primarily affected by Type I collagen defects.
*Lens*
- The **lens** relies primarily on **crystallin proteins** for its structure, not collagen.
- **Lens dislocation** (ectopia lentis) is associated with **Marfan syndrome** (defective fibrillin-1) and **homocystinuria**, not osteogenesis imperfecta.
Question 13: A 57-year-old woman comes to the physician because of increasing wrinkles on her face and sagging skin. She says that her skin used to be smooth and firm. Examination shows diffuse xerosis and mild atrophy, laxity, and fine wrinkles on the periorbital skin. Which of the following processes is most likely involved in the development of this patient's skin findings?
A. Decreased crosslinking of collagen fibrils
B. Decrease in elastin fiber assembly (Correct Answer)
C. Increase in lipofuscin deposition
D. Increase in fibroblast activity
E. Decrease in lysyl oxidase activity
Explanation: ***Decrease in elastin fiber assembly***
- Aging, particularly due to **photoaging** (chronic sun exposure), leads to degradation of **elastic fibers** in the dermis.
- A decrease in functional **elastin** results in reduced skin elasticity and resilience, manifesting as **wrinkles** and **sagging skin**.
*Decreased crosslinking of collagen fibrils*
- While collagen crosslinking can change with age, a *decrease* in crosslinking would generally make collagen less stable and more susceptible to degradation, which can contribute to aging, but the primary culprit for **laxity** and **loss of recoil** is **elastin degradation**.
- **Increased crosslinking** of collagen, often due to advanced glycation end products, is more directly associated with skin stiffness and reduced flexibility in intrinsic aging, rather than the primary cause of laxity.
*Increase in lipofuscin deposition*
- **Lipofuscin** is an age pigment composed of oxidized lipids and proteins, which deposits in cells, giving them a yellowish-brown appearance.
- While lipofuscin accumulates in aging cells, it contributes to the appearance of **age spots** or "liver spots" (lentigines) and is not primarily responsible for the structural changes like **wrinkles** and **sagging skin**.
*Increase in fibroblast activity*
- An increase in **fibroblast activity** would typically lead to increased synthesis of **collagen** and **elastin**, contributing to skin repair and firmness.
- This is the opposite of what occurs in skin aging, where fibroblast activity generally **decreases** or becomes dysfunctional, leading to reduced extracellular matrix production.
*Decrease in lysyl oxidase activity*
- **Lysyl oxidase** is crucial for **collagen** and **elastin crosslinking**, essential for the stability and integrity of these fibers.
- A decrease in lysyl oxidase activity would impair the proper crosslinking of both **collagen** and **elastin**, leading to weaker, less stable connective tissue, but the primary mechanism for the described clinical findings is **elastin degradation** and *disorganized elastin fiber assembly* rather than just reduced crosslinking of existing fibers.
