Genetics - Dysmorphology

Question 1

 A 40 year old male had a lesion on his abdomen removed. Pathology identified it as a Neurofibroma. On physical exam the patient has 10 café au lait spots and axillary freckling.
 Which is the most likely diagnosis

A. Tuberous Sclerosis
B. Noonan syndrome
C. Neurofibromatosis
D. Normal Variant
E. Klinefelter Syndrome

Answer 1

C. Neurofibromatosis

Question 2

What is the inheritance of neurofibromatosis?

Answer 2

Autosomal Dominant

Question 3

What are Lisch nodules?

Answer 3

Iris hamartomas that are associated with neurofibromatosis

Question 4

What bone defect can be seen in neurofibromatosis?

Answer 4

Osseous defect of the fibula - can be present in infancy

Question 5

A 22 year old female has a father who was recently diagnosed with Marfan syndrome. He has a mutation of the FBN1 gene. She was found to have the same change to the FBN1 gene. Which of the following is recommended.

A. Renal Ultrasound 
B. Head CT
C. Audiology exam 
D. Echocardiogram 
E. Pulmonary function test

Answer 5

D. Echocardiogram

Question 6

What heart abnormality can be seen in patients with Marfan syndrome?

Answer 6

Mitral Valve Prolapse

Question 7

What is the main cause of morbidity in Marfan syndrome patients?

Answer 7

Aortic Dissection

Question 8

What is the inheritance of Marfan syndrome?

Answer 8

Autosomal Dominant

Question 9

What is the risk for Marfan syndrome patients to pass the disease onto their children?

Answer 9

50%

Question 10

How does losartan act in Marfan syndrome in a beneficial manner?

Answer 10

When fibrillin is abnormal there is up regulation of the angiotensin receptor (AT1) which increases SMAD 2 which increases TBFB, this results in aortic root dilatation.

Losrtan blocks the AT1 receptor.

Question 11

A 3 year old male was diagnosed with autism and cognitive delays. He has a long face, large ears and hypermobile joints. The most likely diagnosis is:

 A. Fragile X syndrome
 B. Down syndrome
 C. 22q11 deletion syndrome
 D. Phenylkeptonuria
 E. Homocystinuria

Answer 11

 A. Fragile X syndrome

Question 12

What is the most common cause of inherited mental retardation?

Answer 12

Fragile X Syndrome

Question 13

What are some features of Fragile X syndrome?

Answer 13

•  Prominent or large ears
•  Long face
•  Prognathism
•  Hyper-extensible joints
• Macro-orchidism

Question 14

Is karyotyping done for Fragile X syndrome?

Answer 14

No

Question 15

What is the characteristic nucleotide repeat in Fragile X?

Answer 15

CGG repeats - over 200 repeats that are found leading to methylation and causing the gene to be non-functional

Question 16

A 5 year old male is having increasing frequency of toe walking. He has difficulty going up stairs. The creatinine kinase was measured at 22,000 (nl 0- 50). Which is the most likely diagnosis?

A. Down syndrome
B. Myotonic Dystrophy 
C. Duchenne Muscular Dystrophy 
D. Fragile X syndrome
E. Pompe disease

Answer 16

C. Duchenne Muscular Dystrophy

Question 17

What is the inheritance of Duchenne Muscular Dystrophy?

Answer 17

X-linked Recessive

Question 18

What is most often the cause of death in Duchenne Muscular Dystrophy?

Answer 18

Heart failure second to dilated cardiomyopathy

Question 19

What is the mutation in Duchenne Muscular Dystrophy?

Answer 19

Dystrophin - no dystrophin is produced

Question 20

A 2 month old female has macroglossia, hemihypertrophy and glabellar hemangioma. Which of the following is the patient at greatest risk for:

A. Fracture
B. Anemia
C. Colon cancer
D. Aortic root dilatation
E. Wilms tumor

Answer 20

E. Wilms tumor

Question 21

What are the features of Beckwith-Wiedeman syndrome?

Answer 21

•  Increased birth weight
•  Hypoglycemia (neonatal)
•  Hypocalcemia
•  Anterior ear creases

Question 22

What do infants born by IVF have increased risk for?

Answer 22

Beckwith-Wiedemann syndrome

Question 23

What is the mutation in Beckwith-Wiedemann syndrome?

Answer 23

Caused by a duplication of the insulin growth factor

receptor (11p)

Question 24

What tumors are patients with Beckwith-Wiedemann at increased risk for?

Answer 24

• Wilms Tumor

- Hepatoblastoma

Question 25

A 3 year old male has gross motor delays. He was diagnosed with Fetal Alcohol syndrome. Which of the following is the most common physical feature:

 A. Macrocephaly
 B. Short stature
 C. Congenital heart defect
 D. Short palbebral fissure
 E. Polydactyly

Answer 25

B. Short stature
D. Short palbebral fissure

Both are correct.

Question 26

What disease are these features associated with:

•  Microcephaly
•  Low birth weight
•  Failure to thrive
•  Long smooth philtrum
•  Thin upper lip
•  Hearing loss
•  Congenital heart defects

Answer 26

Fetal Alcohol Syndrome

Question 27

What is the cause of fetal alcohol syndrome?

Answer 27

Prenatal alcohol exposure