Genetics and Pathophysiology
A 3-year-old boy is found to have a deletion in the DMD gene, resulting in a prematurely truncated dystrophin protein. What type of mutation is this?
What is a frameshift mutation?
A 5-year-old boy stands up from the floor by climbing up his own legs using his arms. What is this maneuver called?
What is the Gower sign?
A child with muscle weakness has a serum enzyme level of 12,000 U/L, far above the normal range. What enzyme is elevated?
What is creatine kinase (CK)?
A 17-year-old with DMD presents with exertional dyspnea and echocardiography shows reduced ejection fraction. What is the most likely cardiac diagnosis?
What is dilated cardiomyopathy?
A newly diagnosed boy with DMD is started on a drug to slow progression of muscle degeneration. What class of drug is used?
What are glucocorticoids (e.g., prednisone)?
A family has multiple male children affected by DMD. The mother is asymptomatic but is a carrier. What is the inheritance pattern?
What is X-linked recessive?
Where does muscle weakness typically begin? Why?
What is the pelvic girdle?
If genetic testing (i.e. MLPA, NGS) yields negative results, but DMD is still highly suspected, what is a follow up test that can be performed to confirm the dx?
What is immunohistochemistry?
A child with DMD has shallow breathing and decreased chest expansion. Weakness of which muscle group explains this?
What is the diaphragm and other respiratory muscles?
What is a machine often prescribed to DMD patients that allows them to easily breathe during sleep, given that there is weakness of the respiratory muscles such as the diaphragm?
What is a BiPAP machine?
At [age range], a patient with DMD is no longer ambulatory.
What is age 10-12 (+/- 2 years)
A child with muscular dystrophy has very large calf muscles that are firm to palpation. What process causes this finding? What is their actual calf strength relative to their calf size?
What is fibrofatty muscle replacement (pseudohypertrophy)?
What is the best test to diagnose the condition that is typically the main cause of death for DMD patients?
What is an echocardiogram?
Bonus: what is the typical prognosis (in years) for treated/untreated DMD patients on average?
A boy with DMD develops a spinal curvature that worsens with growth. What is this complication called?
What is scoliosis?
What mechanism(s) causes the inflammation in DMD that allows glucocorticoids to be standard of care treatment option?
What is "without dystrophin, muscle fibers are fragile and prone to damage during contraction. This leads to repeated cycles of muscle fiber injury and necrosis",
or some paraphrasing of this.
Two patients have mutations in the same gene. One has mild symptoms and late-onset weakness, while the other is wheelchair-bound by age 10. What explains the difference in severity?
What is the absence of functional dystrophin in Duchenne vs partial dystrophin in Becker?
A 10-year-old boy with DMD begins to develop a lumbar spinal curvature while still ambulatory. What musculoskeletal complication does this represent and why does it occur?
What is scoliosis due to muscle weakness and imbalance?
A child with muscular dystrophy has elevated AST and ALT, but no signs of liver disease. What explains these lab findings?
What is muscle breakdown leading to transaminase elevation?
A teenage boy with DMD develops palpitations and fainting spells. What cardiac complication might explain this, and why palpitations?
(For example: "[disease complication] causes [symptom] because of [reason]")
What is arrhythmia due abnormal cardiac fibers (dilated cardiomyopathy)?
What class of drugs is commonly started early to prophylactically manage the most common cause of death of DMD?
What are ACE inhibitors or beta-blockers?
A female carrier of the DMD mutation develops mild muscle cramps and fatigue in her 30s. What is the mechanism behind her symptoms?
What is skewed X-inactivation (lyonization)?
On gait assessment, a boy with DMD sways side to side with a wide stance. What is this type of gait called?
What is a waddling gait?
A pregnant woman has a family history of DMD and wants to test the fetus. What initial procedure, followed by confirmatory test, would ascertain the carrier status or fetal mutation of the fetus?
(Conceptually speaking, no need for specifics if you don't remember the name)
What is prenatal genetic testing (e.g., chorionic villus sampling or amniocentesis with DMD gene analysis)?
In DMD, loss of dystrophin causes sarcolemmal instability and influx of this ion, leading to activation of proteases.
What is Ca2+?
Some more novel drugs like eteplirsen utilize exon skipping mechanisms to treat subtypes of DMD. Why does exon skipping therapy work mechanistically? Open ended question.
It skips over the targeted exon and as a result, also mitigates the downstream effects of frameshifts/nonsense.