Heritable Disorders of the Skeleton and Soft Tissue Flashcards

A comprehensive set of flashcards covering heritable connective tissue and skeletal disorders including Ehlers-Danlos Syndrome, Marfan Syndrome, Osteogenesis Imperfecta, and Chondromalacia Patellae.

What is the general definition of Ehlers-Danlos Syndromes (EDS)?

A heterogeneous group of genetic disorders that weaken the body's connective tissue, presenting with joint hypermobility, skin hyperextensibility, and tissue fragility.

What is the approximate global incidence/prevalence of all Ehlers-Danlos Syndrome types?

$1$ in $5000$ individuals worldwide.

Which genes are typically mutated in the Classical type of Ehlers-Danlos Syndrome?

$COL5A1$ or $COL5A2$ (type V collagen).

Which gene mutation is associated with Vascular Ehlers-Danlos Syndrome (vEDS)?

$COL3A1$ (type III collagen).

Which gene is mutated in Classical-like Ehlers-Danlos Syndrome?

The $TNXB$ gene, which codes for the tenascin-X protein.

What are the two major clinical criteria for a diagnosis of Classical EDS?

1. Skin hyperextensibility and atrophic scarring; 2. Generalized joint hypermobility.

What clinical findings characterize Vascular EDS (vEDS)?

Fragile blood vessels, intestines, and uterus, which can lead to life-threatening ruptures, as well as thin skin with visible veins.

What is the primary cause of death in individuals with vascular EDS?

Arterial rupture.

What specific dermatological management is recommended for patients with EDS?

Careful wound care, often leaving stitches in longer to ensure proper healing.

On which chromosome is the $FBN1$ gene located in Marfan Syndrome?

Chromosome $15$.

What is the role of Fibrillin-1 in the extracellular matrix?

It is a glycoprotein essential for forming microfibrils that provide structural support and elasticity to tissues like the aorta, ligaments, and the eye's lens.

In Marfan Syndrome, what happens when Fibrillin-1 fails to sequester Transforming Growth Factor beta ($TGF-\beta$)?

Active $TGF-\beta$ levels increase, leading to excessive signaling that triggers tissue fibrosis, abnormal cell growth, and breakdown of elastic fibers.

What is 'cystic medial necrosis' in the context of Marfan Syndrome?

A fragmentation of elastic fibers in the aorta that leads to weakening, dilation, and a high risk of dissection or rupture.

What percentage of Marfan Syndrome cases are result from a de novo (spontaneous) mutation?

$25\%$.

According to the Revised Ghent Nosology, what are the two cardinal diagnostic indicators for Marfan Syndrome?

Aortic root enlargement ($Z\text{-score} \ge 2$) and ectopia lentis (dislocated lens).

Which medications are used in Marfan Syndrome to reduce stress on the aorta?

Beta-blockers (e.g., atenolol) and Angiotensin II Receptor Blockers (ARBs, e.g., losartan).

At what aortic diameter is prophylactic surgery typically recommended for adults with Marfan Syndrome?

Approximately $5.0\,cm$.

How do hand and foot features differ between EDS and Marfan Syndrome?

In EDS, hands and feet are normal to small; in MFS, patients exhibit arachnodactyly (long, spider-like fingers).

What is the common name for Osteogenesis Imperfecta (OI)?

Brittle Bone Disease.

Most cases of Osteogenesis Imperfecta are related to mutations in which two genes?

$COL1A1$ and $COL1A2$.

What is the underlying pathophysiology of Osteogenesis Imperfecta?

Decreased quantity or abnormal structure in type 1 collagen leading to decreased bone strength and an abnormal matrix.

What are five common clinical manifestations of Osteogenesis Imperfecta?

1. Fragile bones; 2. Blue sclerae; 3. Early deafness; 4. Dental imperfections (dentinogenesis imperfecta); 5. Joint hypermobility.

Which type of Osteogenesis Imperfecta is considered the perinatal lethal form?

Type II.

Typical X-ray findings for a patient with Osteogenesis Imperfecta include what?

Multiple fractures in different stages of healing.

Which class of medication is used in the management of OI to increase bone mineral density and reduce fracture rates?

Bisphosphonates.

What is Chondromalacia Patellae?

A disorder of overuse involving articular changes to the patella leading to anterior knee pain.

What specific activities typically worsen the pain associated with Chondromalacia Patellae?

Climbing or descending stairs, squatting, kneeling, or prolonged sitting with knees bent.

How is the patellar grind test performed during a physical exam for Chondromalacia Patellae?

The examiner applies downward pressure above the patella while the supine patient contracts the quadriceps; pain indicates a positive test.

What is the first-line management for Chondromalacia Patellae?

Non-operative treatment including rest, activity modification, NSAIDs, and physical therapy focused on quadriceps strengthening (vastus medialis).

What are the specific 'key clues' for OI, EDS, Marfan, and Chondromalacia patellae according to the 'Key Takeaways for the Boards'?

OI: Blue sclerae and multiple fractures; EDS: Hyperextensible skin and hypermobile joints; Marfans: Tall stature, lens dislocation, and aortic risk; Chondromalacia patellae: Anterior knee pain worsened by stairs.