CASE NUMBER 1
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Clinical History: A 30-year-old man presented to the emergency department with a one-month history of flank tenderness and vague abdominal pain. Physical exam revealed palpable kidneys and ultrasound showed cystic changes in both kidneys. Urinalysis showed 2+ proteinuria. The patient progressed to end stage renal failure and was maintained on dialysis until a transplant kidney became available.
Image Gallery:
(Summary of Gross Findings - click here)
The kidney is markedly enlarged. The parenchyma has been replaced by multiple cysts which vary in size. The cysts are filled with fluid.
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(Summary of Microscopic Findings - click here)
This is a complete hemi section of the kidney. Examination reveals that the entire kidney is replaced by multiple cysts up to several centimeters in diameter. Microscopic examination shows the cysts to be markedly dilated tubules that contain granular eosinophilic material (probably protein) and in some cases, red blood cells. The glomeruli, are compressed.
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(Review Normal Histology - click here)
Norm No. 2
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The kidney excretes soluble waste from the body and controls electrolyte balance. It consists of the cortex and the medulla. Within the outer cortex, glomeruli with delicate capillary loops are seen. The basement membrane is thin and without inflammation or thickening. Bowman’s capsule that surrounds the glomerulus is thin. The interstitium demonstrates no evidence of inflammation or fibrosis. In the areas between the glomeruli, tubules and arterioles are seen. The tubules are intact. The vessels exhibit no narrowing or wall thickening. The inner medulla of the kidney contains only tubules and blood vessels. Larger arteries and veins are located at the interface between cortex and medulla.
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1-1. What is the differential diagnosis?
ANSWER
1-2. Which of the following genetic abnormalities is most likely to be the etiology this patient’s disease?
- Autosomal dominant mutation
- Autosomal recessive mutation
- Genomic imprinting
- Germline mosaicism
- Random X inactivation
ANSWER
1-3. Which of the following genes is most likely mutated in this patient?
- CFTR
- FBN1
- PAH
- PKD1
- PKHD1
ANSWER
1-4. This patient is at greatest risk for which of the following?
- Aortic stenosis
- Berry aneurysms
- Hepatic fibrosis
- Portal hypertension
- Renal cell carcinoma
ANSWER
CASE NUMBER 7
(no virtual slide for this case)
Clinical History: A 48-year-old woman presents to the emergency department in labor. She has had no prenatal care. Delivery of the full-term infant is uncomplicated. An image of the neonate is provided.
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7-1. What is the differential diagnosis?
ANSWER
Clinical History (continued): Cytogenetics is performed and shows that some of the patient’s cells have a normal karyotype(46,XX) and others are 47,XX, +21.
7-2. Which of the following processes best accounts for this patient’s karyotype?
- Amplification
- Chromosomal deletion
- Lyonization
- Mosaicism
- Premutation
ANSWER
7-3. Which of the following is the most likely etiology of this finding (ie. answer to question 2)?
- Amplification of the short arm of chromosome 21
- Excess trinucleotide repeats
- Meiotic disjunction
- Mitotic disjunction
ANSWER
7-4. Which of the following is most strongly associated with risk of having a child with this disease?
- Advanced maternal age
- In utero alcohol exposure
- Insufficient folate
- Oligohydramnios
- Toxoplasma infection
ANSWER
7-5. For which of the following is this patient at greatest risk?
- Alzheimer disease
- Hyperlipidemia
- Hypocalcemia
- Infertility
- Retinoblastoma
ANSWER
CASE NUMBER 6 - slide courtesy of UIndiana
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Clinical History: A 2-year-old girl is brought to the pediatrician by her parents who noticed that she had a large right-sided abdominal mass. A CT scan was performed. Subsequently, the patient underwent a nephrectomy.
Image Gallery:
(Summary of Imaging Findings - click here)
The CT scan shows a heterogeneous mass arising from the right kidney. A small sliver of residual kidney can be seen superomedial to the mass.
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(Summary of Gross Findings - click here)
Grossly, there is a solitary heterogeneous, lobulated, yellow-tan mass that distorts the kidney. The tumor appears well circumscribed. There are areas of hemorrhage and necrosis. Residual kidney can be seen at the top of the image.
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(Summary of Microscopic Findings - click here)
The slide shows a portion of normal kidney. The tumor displays triphasic histology: blastemal (small blue cells), stromal (spindle cells that are “fibroblastic” and often myxoid which is to say “mucoid”) and epithelial (glomerular structures and abortive tubules). Heterologous elements such as adipose tissue, cartilage and osteoid, are not seen here.
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(Review Normal Histology - click here)
Norm No. 2
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The kidney excretes soluble waste from the body and controls electrolyte balance. It consists of the cortex and the medulla. Within the outer cortex, glomeruli with delicate capillary loops are seen. The basement membrane is thin and without inflammation or thickening. Bowman’s capsule that surrounds the glomerulus is thin. The interstitium demonstrates no evidence of inflammation or fibrosis. In the areas between the glomeruli, tubules and arterioles are seen. The tubules are intact. The vessels exhibit no narrowing or wall thickening. The inner medulla of the kidney contains only tubules and blood vessels. Larger arteries and veins are located at the interface between cortex and medulla.
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6-1. What is the differential diagnosis?
ANSWER
6-2. Which of the following is most closely associated with poor prognosis in patients with this disease?
- Deletion of phenylalanine codon at position 508 (deltaF508)
- Diffuse anaplasia
- Intrauterine exposure to phenylalanine
- NMYC amplification
- X-linked inheritance
ANSWER
6-3. Which of the following genes is most commonly mutated in this tumor?
- CFTR
- FMR1
- IGF2
- RB
- WT1
ANSWER
6-4. Which of the following entities, associated with this tumor, is a disorder of genomic imprinting?
- Beckwith-Wiedemann syndrome
- Denys-Drash syndrome
- Fragile X syndrome
- Klinefelter syndrome
- WAGR (Wilms tumor, aniridia, genital abnormalities and mental retardation) syndrome
ANSWER
CASE NUMBER 539 - slide courtesy of UMich
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Clinical History: A newborn baby is noted to have meconium ileus. His mother notices that when she kisses him, his skin tastes salty. Throughout childhood, he experiences persistent lung infections, chronic cough and obstructive pulmonary disease and, later in life, he develops exocrine pancreatic insufficiency with manifestations of malabsorption. He dies from cor pulmonale and an autopsy is performed.
Image Gallery:
(Summary of Gross Findings - click here)
The bronchioles are extremely dilated and there are areas with extensive mucus plugging. The pulmonary parenchyma is consolidated by a combination of pneumonia and secretions.
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(Summary of Microscopic Findings - click here)
The bronchioles are dilated and filled with mucus admixed with abundant acute and chronic inflammatory cells. There is marked hyperplasia and hypertrophy of the mucus-secreting cells.
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(Review Normal Histology - click here)
Norm No. 24 Lung
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The primary function of the lung is gas exchange. Therefore, alveoli have thin walls lined by thin flat pneumocytes and endothelial cells. There is no thickening or fibrosis of the interstitium. The bronchioli are lined with basally oriented ciliated columnar epithelium. The bronchi are lined by similar epithelium. There are mucous glands within the submucosa. The bronchial smooth muscle is not hypertrophied. The pulmonary vessels are patent with no evidence of intimal thickening or muscular hyperplasia.
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539-1. Based on the clinical presentation what is the differential diagnosis?
ANSWER
539-2. Which of the following genes is most frequently mutated in this disease?
- APC
- CFTR
- COL3A1
- FMR1
- LDLR
ANSWER
539-3. Which of the following best accounts for the pulmonary findings in this patient?
- Decreased chloride secretion in respiratory epithelium
- High-volume surface fluid layer coating respiratory mucosa cells
- Hyperplasia of bronchial smooth muscle
- Hypoplasia of bronchiolar cartilage
- Increased water and sodium secretion in respiratory epithelium
ANSWER
539-4. Which of the following is most commonly found in patients with this disease?
- Cherry red macula
- Hepatosplenomegaly and bone lesions
- Increased plasma LDL
- Light colored hair and skin
- Pseudomonas aeruginosa infection
ANSWER
CASE NUMBER 601 - slide courtesy of UMich
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Clinical History: A 44-year-old man has developed increasing arthritis pain, swelling of the feet, and reduced exercise tolerance over the past 3 years. He has smoked 1 pack of cigarettes per day for 20 years. Physical exam reveals hepatomegaly. Laboratory studies include serum glucose of 201 mg/dL, creatinine 1.1 mg/dL and ferritin 893 ng/mL.
601-1. Which of the following tests would be the best one to order at this time?
- Transferrin saturation
- Chest X-ray
- MRI of the foot
- Joint aspirate
- Glucose tolerance test
ANSWER
601-2. Why is the ferritin level elevated?
- He has iron deficiency
- Excess ferritin comes from cigarette smoke
- This is a consequence of early diabetes
- There is an excess of iron in the body
- He is in renal failure
ANSWER
Clinical History (continued): A chest radiograph shows bilateral pleural effusions, pulmonary edema, and cardiomegaly. Abdominal CT confirms hepatomegaly.
He undergoes a liver biopsy, and the microscopic appearance of a biopsy specimen stained with Prussian blue is shown.
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601-3. What is the diagnosis?
ANSWER
601-4. Which of the following is the most appropriate information to give this patient?
- You should take iron supplements
- A cholecystectomy should be performed
- Your siblings may be at risk of developing the same condition
- You will most likely develop acute fulminant hepatitis
- Smoking for many years has led to this condition
ANSWER
GENETIC DISORDERS Review Items
Key Vocabulary Terms (click here to search any additional terms on Stedman's Online Medical Dictionary)
LEARNING OBJECTIVES
Absolutely critical information you must know to practice medicine is in bold font.
Important information that will be needed for routine patient care is in regular font.
Information about less common diseases that you may encounter in clinical practice and that will probably appear on examinations is in italics
- Identify factors which influence the type and extent of congenital anomalies produced by teratogenic agents.
- List a maternal therapeutic agent which has been implicated in each of the following malformations:
- Describe the morphologic features of the embryopathies associated with ingestion of the following substances during pregnancy:
- alcohol
- hydantoin (dilantin)
- Discuss the possible influence on oogenesis and spermatogenesis of maternal and paternal exposure to toxic agents.
- Discuss five common genetic abnormalities in terms of: pathogenesis, common features, classification and give examples of each.
- List three examples of each of the following types of genetic diseases:
- simple (autosomal) dominant
- simple (autosomal) recessive
- sex-linked recessive
- multifactorial inheritance
- Given a family history or pedigree, indicate the most likely mode of inheritance:
- autosomal dominant
- autosomal recessive
- sex-linked dominant
- sex-linked recessive
- Given the mode of inheritance or a family history involving a disease with classic Mendelian inheritance, predict the likelihood of various phenotypes and genotypes in family members.
- Discuss the use of chromatin (Barr) body identification in the recognition and diagnosis of chromosome disorders.
- Compare chromosome analysis (karyotyping) and Barr body count (buccal smear)
- basic steps in performance of test
- appropriateness in various types of clinical situations
- costs and time involved
- accuracy
- Outline pathogenetic mechanisms of importance in the production of:
- mutations
- acquired congenital anomalies
- nondisjunction
- Discuss chromosomal abnormalities in terms of:
- pathogenesis
- classification
- specific features of the more common examples
- List probable causes and examples of mutations and acquired congenital anomalies.
- Given photographs of karyotypes, determine the abnormalities in sex or autosomal chromosomes.
- Distinguish on the basis of clinical signs, symptoms and karyotype among:
- Compare translocation and mosaic types of Down syndrome on the basis of:
- karyotype
- maternal factors
- inheritance
- Compare pseudo- and true hermaphroditism on the basis of genetic and gonadal morphology.
- Compare rubella infection and thalidomide ingestion in pregnant women in terms of epidemiology and developmental effects on the embryo and fetus.
- Discuss the usefulness of the following laboratory tests in regard to genetic disorders and congenital malformations:
- amnionic fluid analysis
- tissue culture
- buccal smear
- chromosomal analysis
- Discuss the following lysosomal storage diseases in terms of enzyme deficiency, stored metabolite and clinical phenotype:
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