Genetic and Pediatric Diseases Practice Questions
20 free Genetic and Pediatric Diseases practice questions for the USMLE Step 1. Tap an option to answer — you get instant feedback, the correct answer, and a detailed explanation for every question.
Which of the following is the genetic basis of Down syndrome (most common form)?
- A Autosomal recessive mutation in a single gene
- B Extra copy of chromosome 21 (trisomy 21)
- C Deletion of long arm of chromosome 5
- D X-linked recessive deletion
Correct answer: Extra copy of chromosome 21 (trisomy 21)
Down syndrome most commonly results from nondisjunction leading to an extra copy of chromosome 21 — trisomy 21 — affecting all or most cells. This chromosomal aneuploidy underlies the syndrome.
Which of these is a classic clinical feature commonly seen in Down syndrome patients?
- A Macroorchidism (enlarged testes)
- B Short stature with a webbed neck
- C Intellectual disability with an atrioventricular septal defect
- D Tall stature with disproportionately long limbs
Correct answer: Intellectual disability with an atrioventricular septal defect
Individuals with Down syndrome often have intellectual disability and congenital heart defects, especially atrioventricular septal defects. These are among the most frequent phenotypic manifestations of trisomy 21.
Cystic fibrosis (CF) is inherited by which pattern, and what is the primary defect in CF?
- A Autosomal dominant; defective collagen synthesis
- B Autosomal recessive; defective CFTR chloride channel
- C X-linked recessive; absent dystrophin
- D Mitochondrial inheritance; defective oxidative phosphorylation
Correct answer: Autosomal recessive; defective CFTR chloride channel
CF is an autosomal recessive disease caused by mutations in the CFTR gene, leading to defective chloride ion channels; this results in thick, sticky mucus production, especially affecting lungs and pancreas.
Which organ systems are most characteristically affected in cystic fibrosis, leading to chronic clinical problems?
- A Brain and spinal cord (central nervous system)
- B Lungs and pancreas (respiratory and digestive systems)
- C Bones and joints (musculoskeletal system)
- D Liver and spleen (hepatic and lymphoid)
Correct answer: Lungs and pancreas (respiratory and digestive systems)
CF causes thick mucus secretions that obstruct airways leading to recurrent lung infections, and also impair pancreatic exocrine function causing malabsorption and digestive problems.
Sickle cell disease (SCD) is caused by a mutation in which gene product, and what is the primary pathologic change in red blood cells?
- A CFTR channel defect causing thick mucus
- B Hemoglobin β-chain defect causing rigid sickled cells
- C Hexosaminidase A deficiency with neuronal lipid buildup
- D Fibrillin-1 defect causing weak connective tissue
Correct answer: Hemoglobin β-chain defect causing rigid sickled cells
SCD arises from a point mutation in the β-globin gene, causing abnormal hemoglobin (HbS). Under low oxygen tension, red blood cells distort into sickle shapes — rigid and prone to hemolysis and vaso-occlusion.
Which of the following genetic disorders often leads to progressive neurodegeneration in infancy or early childhood due to enzyme deficiency in the central nervous system?
- A Phenylketonuria (PKU)
- B Tay–Sachs disease
- C Turner syndrome
- D Marfan syndrome
Correct answer: Tay–Sachs disease
Tay–Sachs disease is a fatal autosomal recessive disorder caused by deficiency of hexosaminidase A; accumulation of GM2 ganglioside leads to progressive neuronal destruction and neurodegeneration early in life.
Which syndrome is caused by the complete or partial loss of one X chromosome in a genetically female individual and often results in short stature, infertility and congenital heart defects?
- A Klinefelter syndrome
- B Turner syndrome
- C Down syndrome
- D Fragile X syndrome
Correct answer: Turner syndrome
Turner syndrome results from monosomy X (45, XO) and presents in females with short stature, gonadal dysgenesis (infertility), and frequent congenital cardiovascular anomalies.
Which of the following best describes the inheritance pattern of most classical inborn errors like cystic fibrosis, sickle cell disease, and Tay–Sachs disease?
- A Autosomal dominant
- B Autosomal recessive
- C X-linked recessive
- D Mitochondrial
Correct answer: Autosomal recessive
These disorders are typically inherited in an autosomal recessive manner — requiring two defective alleles (one from each parent) for the disease phenotype to appear.
Marfan syndrome commonly results from mutations in the FBN1 gene. Which tissue abnormality primarily accounts for its characteristic aortic aneurysm risk?
- A Defective collagen cross-linking in the aorta
- B Defective fibrillin-1 weakening aortic elastic fibers
- C Excess mucopolysaccharide deposition in vessel walls
- D Hyperplasia of smooth muscle in the aortic wall
Correct answer: Defective fibrillin-1 weakening aortic elastic fibers
FBN1 mutations impair production of fibrillin-1, a structural component of elastic fibers; weakened elastic fibers in the aortic wall predispose to aortic aneurysm and dissection in Marfan syndrome.
Which of the following genetic diseases arises from genomic imprinting or uniparental disomy rather than simple gene mutation or chromosome number change?
- A Down syndrome
- B Prader–Willi syndrome
- C Sickle cell disease
- D Cystic fibrosis
Correct answer: Prader–Willi syndrome
Prader–Willi syndrome results from absence of active paternal genes on chromosome 15 (due to paternal deletion or maternal uniparental disomy), an imprinting disorder — unlike typical single-gene or chromosomal disorders.
Which pediatric genetic condition is most likely when a newborn has exocrine pancreatic insufficiency plus bone marrow dysfunction and short stature (but not classic CF)?
- A Shwachman–Diamond syndrome
- B Turner syndrome
- C Tay–Sachs disease
- D Down syndrome
Correct answer: Shwachman–Diamond syndrome
Shwachman–Diamond syndrome is an autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow failure or cytopenias, growth retardation, and skeletal abnormalities, distinguishing it from CF.
Which of the following statements about chromosomal disorders is TRUE?
- A They always arise from single-gene point mutations
- B They may involve extra, missing, or altered chromosomes
- C They are usually inherited via simple recessive patterns
- D They are never compatible with survival
Correct answer: They may involve extra, missing, or altered chromosomes
Chromosomal disorders stem from numerical (extra or missing) or structural (deletion, translocation, inversion) abnormalities of chromosomes — affecting many genes at once.
In a pedigree showing an X-linked recessive disease such as Duchenne muscular dystrophy, which parent transmits the defective gene to an affected male child?
- A Father only
- B Mother only
- C Both parents equally
- D Impossible to determine
Correct answer: Mother only
X-linked recessive diseases are transmitted by carrier mothers; an affected male receives the mutant X chromosome from his mother, while the father contributes Y.
Which metabolic pediatric disease results from inability to degrade an amino acid, leading to intellectual disability unless detected by newborn screening and treated early with dietary restriction?
- A Cystic fibrosis
- B Phenylketonuria (PKU)
- C Marfan syndrome
- D Turner syndrome
Correct answer: Phenylketonuria (PKU)
Phenylketonuria (PKU) is an inborn error of metabolism due to phenylalanine hydroxylase deficiency; if untreated, phenylalanine accumulates causing intellectual disability — early detection and dietary management prevent this.
Which genetic condition tends to have more severe expression of disease in males because of having only one X chromosome?
- A Down syndrome (trisomy 21)
- B Turner syndrome (monosomy X)
- C X-linked recessive disorders
- D Autosomal recessive disorders
Correct answer: X-linked recessive disorders
In X-linked recessive disorders, males (XY) with one mutated X-linked gene manifest disease fully because they lack a second normal copy; females (XX) often are carriers with milder or no symptoms.
A newborn male baby presents with micrognathia, downward slanting palpebral fissures, malformed ears and cleft palate, but normal intelligence. Which disorder is most consistent with these findings?
- A Turner syndrome
- B Treacher Collins syndrome
- C Down syndrome
- D Prader–Willi syndrome
Correct answer: Treacher Collins syndrome
Treacher Collins syndrome is an autosomal dominant craniofacial disorder characterized by mandibulofacial dysostosis — normal intelligence but ear, cheekbone, jaw, palate and ear anomalies.
Which of the following is a common complication in children with Down syndrome that warrants early cardiac evaluation?
- A Hypertrophic cardiomyopathy
- B Atrioventricular septal defect
- C Tetralogy of Fallot without cyanosis
- D Marfan-type aortic root aneurysm
Correct answer: Atrioventricular septal defect
AVSD is the most frequent congenital heart defect in Down syndrome, occurring in a large proportion of affected infants — early detection is crucial for management.
Which feature differentiates a chromosomal disorder from a single-gene disorder in genetic disease classification?
- A Chromosomal disorders always show autosomal recessive inheritance
- B They involve abnormalities of chromosome number or structure
- C Single-gene disorders never affect metabolic pathways
- D Chromosomal disorders are invariably lethal
Correct answer: They involve abnormalities of chromosome number or structure
Chromosomal disorders arise from numerical or structural abnormalities (e.g., extra chromosome, deletion, translocation) that impact many genes simultaneously, whereas single-gene disorders are due to mutations in a single gene.
Which of the following syndromes is an example of a non-Mendelian, imprinting or uniparental disomy disorder rather than classic autosomal or chromosomal abnormality?
- A Cystic fibrosis
- B Prader–Willi syndrome
- C Turner syndrome
- D Sickle cell disease
Correct answer: Prader–Willi syndrome
Prader–Willi syndrome typically arises from lack of paternal allele expression on chromosome 15 — either by paternal deletion or maternal uniparental disomy — an imprinting disorder distinct from classic Mendelian inheritance.
Which pediatric genetic disease is characterized by progressive destruction of motor neurons leading to muscle weakness, often inherited in an X-linked pattern?
- A Tay–Sachs disease
- B Duchenne muscular dystrophy
- C Cystic fibrosis
- D Down syndrome
Correct answer: Duchenne muscular dystrophy
Duchenne muscular dystrophy is an X-linked recessive disorder causing loss of dystrophin, leading to progressive muscle degeneration and weakness. Males are primarily affected due to X-linked inheritance.