Genetic disorders — MCQs

A 5-year-old girl with Down syndrome presents with fatigue, pallor, and hepatosplenomegaly. Complete blood count shows WBC 45,000/μL with 80% blasts, hemoglobin 6.5 g/dL, and platelets 25,000/μL. Flow cytometry reveals blasts positive for CD19, CD10, and TdT. Cytogenetics show t(12;21) in addition to trisomy 21. Her parents ask about prognosis compared to children without Down syndrome. Synthesizing genetic and prognostic factors, what is the most accurate statement?

A 16-year-old boy with Duchenne muscular dystrophy has progressive respiratory failure. His forced vital capacity is 25% predicted, and he requires BiPAP 18 hours daily. He develops pneumonia requiring intubation. After 3 weeks, he cannot be weaned from the ventilator. The pulmonologist recommends tracheostomy for long-term ventilation. The patient has normal cognition and states he does not want tracheostomy or prolonged ventilation, preferring comfort measures. His parents insist on tracheostomy. Evaluate the appropriate course of action.

A newborn undergoes screening and is found to have elevated 17-hydroxyprogesterone (17-OHP) levels. Follow-up testing confirms severely elevated 17-OHP, elevated ACTH, low cortisol, and low aldosterone. Karyotype is 46,XX. Genital examination shows clitoromegaly and partial labial fusion. The parents ask about gender assignment and immediate management. Evaluate the comprehensive management approach.

A 10-year-old girl with Marfan syndrome presents with sudden onset chest pain and dyspnea. She has a history of aortic root dilation (4.2 cm) and has been on atenolol therapy. Vital signs show BP 90/60 mmHg, HR 120/min. CT angiography reveals Stanford Type A aortic dissection. She requires emergency surgery but her parents are Jehovah's Witnesses and refuse blood transfusion. The surgical team estimates 80% mortality without transfusion versus 15% with transfusion. Analyze the ethical and legal approach.

A 4-year-old boy presents with recurrent bacterial infections, eczema, and thrombocytopenia with small platelets. Laboratory evaluation shows IgE 2,000 IU/mL, IgM low, and IgA normal. Flow cytometry reveals absent CD43 on T-cells. Genetic testing confirms a mutation in the WAS gene. His 2-year-old brother is asymptomatic but genetic testing shows he is also affected. Analyzing the genotype-phenotype correlation, what explains the phenotypic difference?