Clinical Genetics - General = Miscellaneous Differentials to Know (TRANSFERRED)

Question 1

Reference: Genetics residents in-training examination - March 2020 (Spring 2020)

You are seeing an 18 years boy for recurrent pneumothorax. He is also known for a cerebrovascular accident at the age of 6, in an infectious context, and mild intellectual disability.

1. State 5 disorders that are part of the differential diagnosis for recurrent pneumothorax. For each, name the at least one gene involved and the inheritance pattern.
2. The cardiac US shows mitral valve prolapse and downward ectopia lentis is seen on ophthalmologic evaluation. Name three diagnostic tests that you will request for your patient.
3. What is your most probable diagnosis? And what will be the management of the patient? What is the risk for his descendance?

Answer 1

1)
- Homocystinuria due to cystathionine beta-synthase deficiency, CBS, AR

• Costello syndrome, HRAS, AD
• Birt-Hogg-Dube syndrome, FLCN, AD
• Loeys-Dietz syndrome, TGFB2, TGFBR2, TGFBR1, TGFB3, SMAD3, AD
• Marfan syndrome, FBN1, AD
• Ehlers-Danlos syndrome, vascular type, COL3A1, AD
• Alpha-1-antitrypsin deficiency, SERPINA1, AR
• Cutis laxa?
• CF?

2)
CGH, Marfan syndrome (FBN1), total homocysteine

3)
- Homocystinuria due to CBS deficiency.

• Treatment with betaine, low methionine, cystine supplemented diet for pyridoxine non-responders and pyridoxine supplementation for pyridoxine responders.
• The risk is low, the condition is rare, depends on his partner carrier status.