CASE 1

History:

A six-year-old child is evaluated because of an enlarged abdomen. Physical examination reveals hepatosplenomegaly and lymphadenopathy. There is no history of recent infection. The child's vital signs are: T 36.3 C, R 16, P 77, BP 90/60 mm Hg. Developmental milestones are normal, and the child is doing well in the first year of school. A complete blood count is performed and shows WBC count 2300/microliter, Hgb 10.6 g/dL, Hct 32.4%, MCV 94, and platelet count 83,000/microliter. A bone marrow biopsy is performed. Later, a splenectomy is performed.

Image 1.1

Image 1.2

Image 1.3

Questions:

1. What is the underlying inherited disease process? What is the pattern of inheritance?

2. What is the biochemical defect?

3. What is the significance of the child's performance in school? What does this indicate regarding the prognosis?

4. What would you expect to find in a more severe form of this disease?

CASE 2

History:

A 30 year old man feels crushing substernal chest pain one morning. After a couple of hours at work, the pain persists. He has diaphoresis and dizziness. He goes to a local ER. An EKG shows T wave inversion and ST segment elevation. His brother had a similar experience a year ago.

Image 2.1

Image 2.2

Image 2.3

Questions:

1. What laboratory test would be helpful to confirm your diagnosis?

2. What factors suggest a genetic basis for this illness?

3. What disease is suggested by these findings? What is the incidence

4. What labortory test would confirm this?

5. What is the pathophysiology for this condition?

6. Is this disease recessive or dominant?

Image 2.4

CASE 3

History:

A 9-month-old infant has not met developmental milestones for activity. In fact, he has exhibited a loss of motor skills in the past month, along with decreased vocalization and decreased awareness. On physical examination, the baby's head is slightly larger for age than normal. He exhibits an increased startle reaction (quick extension of the arms and legs, frequently with clonic movements).

On funduscopic examination, the findings are abnormal. The baby's condition does not improve,becoming blind, unable to respond to stimuli, and decerebrate, and death occurs from an acute pneumonia at age 20 months.

Image 3.1

Image 3.2

Image 3.3

Questions:

1. What kind of genetic abnormality is most likely to be present?

2. What specific genetic abnormality is present?

3. What is the pathogenesis of this disease?

4. What is the probability that there is no familial history for this disease?

5. What are the patterns of this disease?

6. What is the role of prenatal testing in this case?

CASE 4

History:

A 25 year old man has multiple, irregular lightly pigmented 1 to 5 cm macular (flat) skin lesions scattered on the skin of his trunk and extremities. He also has multiple firm 0.3 to 1 cm skin nodules that are not painful, but are disfiguring. He develops an S-shaped curvature to his spine. At age 25 he notes pain and swelling of his right wrist. An MRI scan of his right arm demonstrates a 3 cm mass lesion eroding the ulna.

Image 4.1

Image 4.2

Image 4.3

Questions:

1. What inheritance pattern would you suspect in this case?

Image 4.4

2. Explain the absence of a family history for this disorder.

3. What is the molecular basis for this disease?

4. Name the lesions present.

5. What is the most likely diagnosis for the mass involving the right arm?

CASE 5

History:

A 3-year-old boy is noted to have increasing difficulty with movement, even walking, due to increasing pain and diminished joint mobility. His knees, ankles, and elbows seem to be affected the most. When he suffers even a small scratch or cut, bleeding continues for more than 20 minutes. A hematoma forms with minimal trauma. Wound healing is poor. On physical examination, joints of extremities show diminished range of motion. No petechial hemorrhages or ecchymoses are noted. The remainder of the exam is normal.

A CBC shows Hgb 13.1 g/dL, Hct 39.4%, MCV 90 fL, platelet count 272,000/microliter, and WBC count 7730/microliter. The prothrombin time is 13.2 sec (normal 12.6) and partial thromboplastin time 66 sec (normal 25).

Questions:

1. What is the inheritance pattern for this genetic disease?

Image 5.1

2. What is the basis for this genetic disease?

3. What laboratory testing will help to identify this disease?

4. What is the organ involvement of this disease?

5. What is the prognosis for this disease?

CASE 6

History:

A 19 year old girl is taller than all her siblings. She has difficulty with vision in her left eye, which an ophthalmologist has diagnosed as ocular lens dislocation. On auscultation of the chest, there is a mid-systolic click heart murmur.

Image 6.1

Image 6.2

Image 6.3

Questions:

1. What is the pathogenesis for these findings?

2. If no other family members are similarly affected, then how can this disease be genetic?

Image 6.4

3. What is causing the heart murmur?

4. What is the most life-threatening complication?

5. How can you explain clinical differences in the appearances of persons with this disorder?

6. What is the significance of this diagnosis on her insurability?

CASE 7

History:

A 14-year-old child, normal at birth, is noted to have bilateral hearing loss. Audiometry reveals mixed conductive and sensorineural hearing loss on both the right and the left. A CT scan of the head reveals maldevelopment of both middle ears with deficient ossification. She learns to use hearing aids. Further history reveals that her dentist has tried various whiteners to subdue the yellow-brown color of her teeth, which have a slight bell-shaped appearance.

Her optometrist noted that her sclerae have a peculiar steel grey color, but her vision is nearly normal (20/40). At age 30 she falls getting out of her car and fractures her left femur. A radiograph reveals that the femur is osteopenic. Bone densitometry reveals osteopenia of all measured sites, typically hip, vertebrae, and wrist.

Image 7.1

Image 7.2

Image 7.3

Questions:

1. What is this condition?

2. What is the inheritance pattern?

Image 7.4

Image 7.5

3. What is the biochemical defect?

4. Explain the appearance of her eyes.

5. What is the reason for the hearing loss?

6. What is the reason for the dental imperfections?

7. What happens to patients with this disorder?