🎯 Theme 5 Exam Practice

A newborn with characteristic features of Down syndrome has a karyotype showing additional chromosome 21 material attached to chromosome 14. The parents are clinically normal and request counselling about future pregnancies. Which additional investigation is most useful for determining their reproductive risk?

A 2-month-old infant is admitted with recurrent vomiting, lethargy and poor feeding. The parents report that an older sibling died during infancy following a similar illness. Initial investigations reveal metabolic acidosis and elevated plasma ammonia. The child is clinically unstable. What is the most appropriate next step?

A 35-year-old woman has recurrent blistering lesions over the backs of her hands, skin fragility and hyperpigmentation. She also has evidence of iron overload. A cutaneous porphyria is suspected. Which management strategy most directly addresses an important contributing factor?

A 25-year-old woman with phenylketonuria attends a preconception consultation. She has not followed her prescribed diet consistently for several years. Her physician explains that poor metabolic control during pregnancy may harm fetal development even if the fetus does not inherit phenylketonuria. What is the most appropriate preventive strategy?

A 4-year-old child with coarse facial features, hepatosplenomegaly and skeletal abnormalities has elevated urinary glycosaminoglycans. The pediatrician wants to confirm the suspected inherited storage disorder and identify its subtype. Which investigation is most appropriate?

An infant with classic galactosemia is started on appropriate dietary treatment after presenting with vomiting, jaundice and poor weight gain. Liver function gradually improves. Which clinical explanation best accounts for this improvement?

A 4-year-old child diagnosed with phenylketonuria during infancy has remained on a controlled dietary programme. The family asks why specialist monitoring is still required despite normal development. Which parameter is most useful for assessing continued metabolic control?

A 7-month-old infant presents with hepatomegaly, recurrent fasting hypoglycemia and mildly elevated liver enzymes. The physician suspects a glycogen storage disorder involving the glycogen debranching enzyme. Further assessment reveals mild muscle weakness. Which additional clinical involvement would be compatible with this disorder?

A 27-year-old woman with a known acute hepatic porphyria is hospitalized with severe abdominal pain, tachycardia and progressive weakness. Her respiratory effort becomes weak during observation. Which complication requires the most urgent clinical attention?

A 23-year-old woman undergoing premarital screening has a hemoglobin concentration of 11.2 g/dL, MCV of 64 fL and a relatively high red-cell count. Hemoglobin analysis reveals elevated HbA2. Her prospective husband has a family history of transfusion-dependent anemia. Which interpretation is most appropriate?

A 12-day-old neonate presents with vomiting, jaundice, poor feeding and hepatomegaly. A metabolic disorder is suspected after the parents report that symptoms began shortly after milk feeding was established. Initial stabilization is started. Which additional investigation would most directly help confirm the suspected metabolic defect?

A couple with a previous child affected by a genetically confirmed inherited disorder requests prenatal testing during their next pregnancy. The pathogenic variants responsible for their child's condition have already been identified. Which laboratory approach would most directly assess whether the fetus carries the relevant familial variants?

A 24-year-old woman presents with recurrent abdominal pain, constipation and episodic limb weakness. During admission, she develops confusion and hyponatremia. Urinary porphobilinogen is markedly elevated. Which mechanism best explains the neurological manifestations?

A 17-year-old boy with suspected Marfan syndrome complains of progressive blurred vision. Examination reveals long slender fingers, increased arm span and pectus carinatum. The ophthalmologist identifies displacement of the crystalline lens. Which underlying tissue abnormality best explains this ocular finding?

A couple is found to carry pathogenic beta-globin variants and receives genetic counselling before marriage. During the consultation, relatives insist that the physician disclose the results to the extended family and advise cancellation of the marriage. The couple wants to understand their reproductive options privately. Which professional response is most appropriate?

A 4-year-old child with hepatomegaly and recurrent fasting hypoglycemia is diagnosed with a hepatic glycogen storage disease. Dietary treatment is initiated. Which finding would best indicate that the nutritional plan is achieving its main therapeutic objective?

A 29-year-old woman has had two pregnancies affected by chromosomal abnormalities. Both parents are clinically healthy, but karyotyping reveals that her husband carries a balanced Robertsonian translocation involving chromosomes 14 and 21. The couple asks why an unaffected father could have children with chromosomal disorders. Which explanation is most appropriate?

A 29-year-old woman with a history of recurrent unexplained abdominal pain develops progressive limb weakness after several days of poor oral intake. Acute hepatic porphyria is suspected. Which factor most likely contributed to the current episode?

A 7-year-old boy with Down syndrome develops progressive pallor, unexplained bruising and intermittent fever. Examination reveals cervical lymphadenopathy and hepatosplenomegaly. His parents initially attribute the symptoms to recurrent childhood infections. Which investigation should be prioritized?

A 32-year-old man has a connective tissue disorder inherited from his affected mother. His sister has a much milder phenotype, while his maternal grandfather had severe cardiovascular complications. All three carry the same pathogenic FBN1 variant. Which genetic principle best explains the differences in clinical severity?

A 15-year-old boy is investigated for persistent hematuria and gradually worsening renal function. He also has bilateral sensorineural hearing impairment. A pathogenic variant affecting type IV collagen has been identified. Which explanation best connects the genetic abnormality to the clinical findings?

A 14-year-old girl presents with marked joint hypermobility, thin translucent skin and easy bruising. Her mother died unexpectedly following spontaneous arterial rupture at a young age. The clinician suspects a severe inherited connective tissue disorder rather than uncomplicated joint hypermobility. Which complication is particularly important to anticipate?

A 3-year-old child has mild developmental delay and some features suggestive of Down syndrome. Chromosomal analysis identifies two cell populations: 46,XX and 47,XX,+21. The parents are confused because the child's physical findings are less pronounced than those of another affected relative. Which interpretation best explains this variation?

A 5-month-old infant has profound hypotonia, difficulty feeding and an enlarged cardiac silhouette. Echocardiography reveals hypertrophic cardiomyopathy. A lysosomal glycogen storage disorder is confirmed. Which treatment targets the underlying enzyme deficiency?

A 5-year-old child presents with progressive behavioral abnormalities, sleep disturbance and deterioration in previously acquired developmental skills. Physical abnormalities are less prominent than the neurological manifestations. Which mucopolysaccharidosis is most likely?

A 15-year-old boy experiences painful muscle cramps during vigorous exercise. He reports that his urine occasionally becomes dark following prolonged physical activity. His resting blood glucose is normal. What is the most likely explanation for his exercise intolerance?

A 7-year-old child presents with short stature, progressive skeletal deformities and restricted joint mobility. Intelligence is relatively preserved. Radiological assessment demonstrates significant skeletal abnormalities, and a mucopolysaccharidosis is suspected. Which subtype is most consistent with this pattern?

A 3-year-old child with a confirmed mucopolysaccharidosis develops progressive gait difficulty and weakness of the lower limbs. Examination reveals increased muscle tone and brisk tendon reflexes. Which complication should be considered?

A 22-year-old man with genetically confirmed Marfan syndrome has progressive enlargement of the aortic root. His cardiologist prescribes a beta-blocker as part of long-term management. Which therapeutic effect is the primary reason for using this drug?

A 10-month-old infant has recurrent fasting hypoglycemia, hepatomegaly and elevated serum lactate. Despite adequate feeding, maintaining blood glucose remains difficult. Which biochemical disturbance most likely explains the elevated lactate?

A fetus has multiple structural abnormalities on ultrasound. Initial chromosomal analysis demonstrates a normal chromosome number without an obvious large structural rearrangement. The fetal medicine specialist discusses a test capable of detecting smaller chromosomal gains and losses. Which investigation is most appropriate?

A 6-year-old child with Down syndrome is brought for routine follow-up. The mother reports reduced activity, constipation and slowing of growth over the preceding months. Examination reveals dry skin and a relatively slow pulse. Which investigation is most appropriate to evaluate a potentially treatable associated condition?

A 19-year-old woman with Marfan syndrome attends follow-up. She has arachnodactyly, mild scoliosis and a previously documented enlarged aortic root. She currently has no cardiovascular symptoms. Which management principle is most important for reducing the likelihood of a life-threatening complication?

A 34-year-old pregnant woman undergoes cell-free DNA screening, which indicates increased risk of trisomy 21. Subsequent diagnostic assessment raises concern about a possible discrepancy between placental and fetal chromosomal findings. Which biological phenomenon can account for this discrepancy?

A 9-year-old child has frequent fractures, short stature and progressive bowing of the lower limbs. Dental examination reveals abnormal dentin formation. The pediatrician explains that the condition results from defective connective tissue within the bone matrix. Which pathological mechanism most directly accounts for the fractures?

A woman is a confirmed carrier of an X-linked recessive disorder. Her husband is unaffected, and they have a healthy daughter. During counselling, she asks whether the daughter could carry the same pathogenic variant despite having no symptoms. Which statement best explains this possibility?

An infant with Down syndrome has delayed language development despite receiving appropriate developmental support. His parents report that he frequently fails to respond when called and has experienced several episodes of ear infection. Which assessment would most directly identify a potentially correctable contributor to his developmental difficulties?

A newborn screening programme identifies an infant with elevated phenylalanine. Further investigations confirm phenylketonuria. The infant is clinically well, and the parents question the need for immediate treatment. What is the strongest reason for initiating dietary management before symptoms appear?

A couple presents for genetic counselling because their first child has a severe autosomal recessive disorder. Both parents are confirmed carriers. Their second child is unaffected, and they believe this reduces the probability of another affected child. Which explanation best addresses their concern?

A 6-year-old boy has progressive coarse facial features, hepatosplenomegaly and restricted joint movements. His parents report frequent respiratory infections and noisy breathing during sleep. Which complication should be specifically assessed because of its potential severity?