PATH - General

Question 1

Cystic fibrosis

Answer 1

Autosomal recessive

defect in *CFTR gene on *chromosome 7; commonly a deletion of Phe508

Most common lethal genetic disease in Caucasian population.

INC Cl− concentration (> 60 mEq/L) in sweat is diagnostic

COMPLICATIONS
Recurrent pulmonary infections, chronic
bronchitis and bronchiectasis–>reticulonodular pattern on CXR.
*Pancreatic insufficiency, malabsorption with steatorrhea, fat-soluble vitamin deficiencies (A, D, E, K), biliary cirrhosis, liver disease. Meconium ileus in newborns.
*Infertility in men (absence of vas deferens, spermatogenesis may be unaffected) and subfertility in
women (amenorrhea, abnormally thick cervical mucus).
*Nasal polyps, clubbing of nails

TX:chest physiotherapy, albuterol, aerosolized dornase alfa (DNAse), and hypertonic
saline facilitate mucus clearance.

Azithromycin used as anti-inflammatory agent.

Pancreatic enzymes for insufficiency.

Question 2

Cri-du-chat syndrome

Answer 2

Congenital microdeletion of short arm of *chromosome 5 (46,XX or XY, 5p−).

Findings: microcephaly, moderate to severe intellectual disability, *high-pitched crying/mewing, epicanthal folds, cardiac
abnormalities (VSD).

Cri du chat = cry of the cat

Question 3

Williams syndrome

Answer 3

Congenital microdeletion of long arm of *chromosome 7 (deleted region includes *elastin gene)

Findings: distinctive “elfin” facies, intellectual disability, hypercalcemia (INC sensitivity to vitamin D), well-developed verbal skills, *extreme friendliness with strangers, cardiovascular problems

Question 4

22q11 deletion syndromes

Answer 4

Microdeletion at *chromosome 22q11–>variable presentations including *Cleft palate, *Abnormal facies, *Thymic aplasia–>T-cell deficiency,
*Cardiac defects, and *Hypocalcemia 2° t parathyroid aplasia

CATCH-22

Due to aberrant development of *3rd and 4th branchial pouches.

• DiGeorge syndrome—thymic, parathyroid, and cardiac defects.
• Velocardiofacial syndrome—palate, facial, and cardiac defects.