USMLE Step 1 Quiz: Chromosomal Disorders
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Chromosomal DisordersQuestion 1 of 20

A 1-month-old infant has a high-pitched cry, microcephaly, and hypotonia. Karyotype shows 46,XY,del(5)(p15). The parents ask what type of chromosomal change this represents compared with trisomy 21. Which statement best explains the difference?

This disorder is due to a structural deletion, whereas trisomy 21 is usually a numerical gain
This disorder is due to monosomy X, whereas trisomy 21 is due to sex chromosome gain
This disorder is due to duplication of 5p, whereas trisomy 21 is due to deletion
This disorder is due to balanced translocation, whereas trisomy 21 is always balanced
This disorder is due to mitochondrial inheritance, whereas trisomy 21 is autosomal recessive
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USMLE Step 1 Quiz

USMLE Step 1 Quiz: Chromosomal Disorders

Practice Chromosomal Disorders in USMLE Step 1 with focused quiz questions that help you check what you know, review explanations, and build confidence with test-style prompts.

What this quiz covers

This quiz focuses on Chromosomal Disorders, giving you a quick way to practice the rules, question types, and explanations that matter most for USMLE Step 1.

How to use this quiz

Try each quiz question before looking at the correct answer. Use the explanations to review missed ideas, then come back to similar questions until the pattern feels familiar.

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Question 1

A 1-month-old infant has a high-pitched cry, microcephaly, and hypotonia. Karyotype shows 46,XY,del(5)(p15). The parents ask what type of chromosomal change this represents compared with trisomy 21. Which statement best explains the difference?

  1. This disorder is due to a structural deletion, whereas trisomy 21 is usually a numerical gain (correct answer)
  2. This disorder is due to monosomy X, whereas trisomy 21 is due to sex chromosome gain
  3. This disorder is due to duplication of 5p, whereas trisomy 21 is due to deletion
  4. This disorder is due to balanced translocation, whereas trisomy 21 is always balanced
  5. This disorder is due to mitochondrial inheritance, whereas trisomy 21 is autosomal recessive

Explanation: This question tests understanding of chromosomal disorders and their genetic mechanisms on the USMLE Step 1. Chromosomal disorders arise from numerical or structural abnormalities, such as trisomies or deletions, leading to various phenotypic manifestations. In this vignette, the patient's symptoms and lab findings suggest cri-du-chat syndrome, supported by the karyotype showing 46,XY,del(5)(p15). The correct choice is A, as it aligns with the clinical and genetic data provided, demonstrating understanding of chromosomal mechanisms. Choice B fails because it inaccurately associates symptoms with monosomy X, a common error when phenotypic traits overlap. To prepare, focus on understanding the genetic basis of common chromosomal disorders and recognize the clinical presentations they typically cause. Practice analyzing karyotypes and relating lab data to clinical findings.

Question 2

A 1-week-old male newborn has hypotonia and mild respiratory distress. He was born at 37 weeks to a 36-year-old mother. Physical exam shows upslanting palpebral fissures, epicanthal folds, flat nasal bridge, and a single palmar crease. Cardiac exam reveals a harsh holosystolic murmur. Echocardiogram shows an atrioventricular septal defect. CBC shows WBC 28.0 ×10^3/µL with circulating blasts; hemoglobin 16.8 g/dL; platelets 95 ×10^3/µL. Karyotype confirms trisomy 21 (47,XY,+21). The neonatologist explains the most likely hematologic complication associated with this chromosomal disorder.

  1. Increased risk of acute lymphoblastic leukemia and transient myeloproliferation (correct answer)
  2. Increased risk of chronic myelogenous leukemia due to t(9;22)
  3. Aplastic anemia due to bone marrow failure from monosomy X
  4. Severe neutropenia due to 5p deletion affecting granulopoiesis
  5. Polycythemia vera due to JAK2 mutation from extra X chromosome

Explanation: This question tests understanding of chromosomal disorders and their genetic mechanisms on the USMLE Step 1. Chromosomal disorders arise from numerical or structural abnormalities, such as trisomies or deletions, leading to various phenotypic manifestations. In this vignette, the patient's symptoms and lab findings suggest Down syndrome, supported by the karyotype showing trisomy 21 (47,XY,+21). The correct choice is A, as it aligns with the clinical and genetic data provided, demonstrating understanding of chromosomal mechanisms. Choice B fails because it inaccurately associates symptoms with chronic myelogenous leukemia, a common error when phenotypic traits overlap. To prepare, focus on understanding the genetic basis of common chromosomal disorders and recognize the clinical presentations they typically cause. Practice analyzing karyotypes and relating lab data to clinical findings.

Question 3

A 4-day-old newborn with hypotonia and facial features consistent with Down syndrome undergoes chromosomal testing. Karyotype shows 46,XX with three copies of chromosome 21 material due to a translocation. The genetic counselor asks about parental testing. Which parental finding would most increase recurrence risk in future pregnancies?

  1. One parent is a balanced Robertsonian translocation carrier involving chromosome 21 (correct answer)
  2. One parent has mosaic 45,X/46,XX with normal fertility
  3. One parent has 47,XXY with infertility and small testes
  4. One parent has a de novo 5p deletion with cat-like cry history
  5. One parent has 47,XYY with normal spermatogenesis

Explanation: This question tests understanding of chromosomal disorders and their genetic mechanisms on the USMLE Step 1. Chromosomal disorders arise from numerical or structural abnormalities, such as trisomies or deletions, leading to various phenotypic manifestations. In this vignette, the patient's symptoms and lab findings suggest Down syndrome due to translocation, supported by the karyotype showing 46,XX with three copies of chromosome 21 material due to a translocation. The correct choice is A, as it aligns with the clinical and genetic data provided, demonstrating understanding of chromosomal mechanisms. Choice B fails because it inaccurately associates symptoms with mosaic Turner syndrome, a common error when phenotypic traits overlap. To prepare, focus on understanding the genetic basis of common chromosomal disorders and recognize the clinical presentations they typically cause. Practice analyzing karyotypes and relating lab data to clinical findings.

Question 4

A phenotypically normal man has a history of two children with different partners, both of whom had multiple congenital anomalies and died in infancy. Karyotype analysis of the man reveals 46,XY,inv(3)(p25q21). His parents have normal karyotypes.

The chromosomal abnormality in this man increases the risk of abnormal offspring due to the potential for producing which of the following?

  1. Gametes with balanced genetic material
  2. Gametes with aneuploidy for chromosome 3
  3. Gametes with duplication and deletion of chromosome 3 segments (correct answer)
  4. Gametes with a ring chromosome 3

Explanation: The man has a pericentric inversion, which involves a segment of a chromosome that includes the centromere. During meiosis, if a crossover event occurs within the inverted segment, it can lead to the formation of recombinant chromosomes that have a duplication of one end and a deletion of the other. Fertilization with such a gamete results in an unbalanced karyotype and is often lethal or causes severe congenital anomalies.

Question 5

A male infant is born with ambiguous genitalia. Physical examination reveals hypospadias and bilateral undescended testes. Karyotype analysis is 46,XY. Further investigation reveals a deletion on the short arm of the Y chromosome.

Deletion of which of the following genes is the most likely cause of this infant's failure to develop normal male external genitalia?

  1. SRY (correct answer)
  2. DAZ
  3. SOX9
  4. WT1

Explanation: The SRY (Sex-determining Region on Y) gene, located on the short arm of the Y chromosome, is the primary genetic switch for male development. It encodes a transcription factor that initiates the differentiation of the gonads into testes. A deletion or mutation in the SRY gene in a 46,XY individual leads to gonadal dysgenesis, where the gonads fail to develop properly into testes. Without functional testes, there is insufficient testosterone and anti-Müllerian hormone production, resulting in the development of female or ambiguous external genitalia.

Question 6

A 6-month-old infant is evaluated for recurrent infections, including oral thrush and pneumonia. The mother reports that the infant has had several episodes of twitching and muscle spasms since birth. Physical examination reveals low-set ears, a small mouth, and a prominent nasal bridge. A chest x-ray shows an absent thymic shadow. Serum calcium is 6.8 mg/dL (normal 8.5-10.2).

The constellation of findings in this patient is best explained by a developmental failure of which embryologic structures due to a chromosomal microdeletion?

  1. First and second pharyngeal arches
  2. Third and fourth pharyngeal pouches (correct answer)
  3. Neural crest cells migrating to the heart
  4. Somites of the axial skeleton

Explanation: This patient presents with features of DiGeorge syndrome (CATCH-22: Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia). This syndrome is caused by a microdeletion at chromosome 22q11.2. The developmental failure of the third and fourth pharyngeal pouches is responsible for the thymic hypoplasia (leading to T-cell immunodeficiency and recurrent infections) and parathyroid hypoplasia (leading to hypocalcemia and tetany).

Question 7

A fetus is diagnosed with Down syndrome via amniocentesis. The karyotype is 47,XY,+21. The parents wish to understand the origin of the extra chromosome. Analysis of polymorphic DNA markers shows that the child inherited two different homologous chromosomes 21 from the mother and one from the father.

This finding indicates that the nondisjunction event occurred during which of the following stages?

  1. Maternal meiosis I (correct answer)
  2. Maternal meiosis II
  3. Paternal meiosis I
  4. An early mitotic division after fertilization

Explanation: The child inherited two different homologous chromosomes from the mother. This means that the mother's homologous pair of chromosome 21 failed to separate during meiosis I. This failure of separation (nondisjunction) resulted in a gamete containing both homologous chromosomes. If nondisjunction had occurred in meiosis II, the gamete would have contained two identical sister chromatids.

Question 8

A newborn male is noted to have a single transverse palmar crease, upslanting palpebral fissures, and a flattened facial profile. On physical examination, a loud holosystolic murmur is heard best at the left lower sternal border. An echocardiogram confirms a complete atrioventricular septal defect. Cytogenetic analysis is performed.

Which of the following is the most likely underlying genetic mechanism responsible for this infant's condition?

  1. Maternal meiotic I nondisjunction (correct answer)
  2. Paternal meiotic II nondisjunction
  3. Post-zygotic mitotic nondisjunction
  4. Balanced Robertsonian translocation in a parent

Explanation: The infant's features are classic for Down syndrome (Trisomy 21). The most common cause of trisomy 21, accounting for over 90% of cases, is nondisjunction of chromosome 21 during maternal meiosis I. This risk increases significantly with advanced maternal age due to the prolonged arrest of primary oocytes in prophase I.

Question 9

A buccal smear from a 25-year-old woman with normal intelligence and fertility is examined under a microscope. The analysis reveals that 30% of her interphase cells contain two Barr bodies. Karyotype analysis is likely to confirm her genetic makeup.

Which of the following karyotypes is most likely in this patient?

  1. 45,X
  2. 46,XX
  3. 47,XXX (correct answer)
  4. 47,XXY

Explanation: A Barr body is an inactivated X chromosome. The number of Barr bodies in a cell is equal to the number of X chromosomes minus one (n-1 rule). A normal female (46,XX) has one Barr body. A patient with two Barr bodies per cell would have three X chromosomes. The karyotype is therefore 47,XXX (Triple X syndrome). Many individuals with this condition have a normal phenotype or mild features like tall stature and learning disabilities.

Question 10

A 28-year-old man and his 26-year-old wife present for genetic counseling after experiencing three consecutive first-trimester miscarriages. Both partners are phenotypically normal. A karyotype analysis of the wife reveals 45,XX,der(14;21)(q10;q10). The husband's karyotype is normal.

This woman is a carrier of a balanced translocation. If she conceives a child with Down syndrome, what is the most likely karyotype of the affected child?

  1. 47,XX,+21
  2. 46,XX,der(14;21)(q10;q10),+21 (correct answer)
  3. 45,XX,-14,-21,+der(14;21)
  4. 46,XX,t(14;21)

Explanation: The mother has a balanced Robertsonian translocation involving chromosomes 14 and 21. During meiosis, she can produce gametes that result in an offspring with translocation Down syndrome. Such a child would inherit her translocated chromosome (der(14;21)) as well as a normal chromosome 21 from her and a normal chromosome 14 and 21 from the father. This results in 46 total chromosomes but three effective copies of the long arm of chromosome 21, leading to the phenotype of Down syndrome. The karyotype is written as 46,XX,der(14;21)(q10;q10),+21.

Question 11

A 16-year-old girl is evaluated for primary amenorrhea and short stature. Her height is below the 3rd percentile. Physical examination reveals a broad chest with widely spaced nipples, a low posterior hairline, and a webbed neck. Cardiovascular examination is notable for a systolic ejection murmur and blood pressure that is 145/90 mmHg in her arms and 100/60 mmHg in her legs.

This patient's condition is most commonly associated with which of the following karyotypes?

  1. 45,X (correct answer)
  2. 47,XXX
  3. 47,XXY
  4. 46,XX with a deletion on the X chromosome

Explanation: The patient's presentation of short stature, primary amenorrhea, webbed neck, and coarctation of the aorta (indicated by the blood pressure differential between arms and legs) is characteristic of Turner syndrome. The most common karyotype for Turner syndrome is 45,X, resulting from the absence of one X chromosome.

Question 12

A male infant is born at 36 weeks gestation to a 22-year-old mother. The infant has multiple anomalies, including microcephaly, a cleft lip and palate, cutaneous scalp defects (cutis aplasia), and polydactyly. Ophthalmic examination reveals micropthalmia. The infant has a poor prognosis and dies within the first week of life.

Karyotyping of this infant would most likely reveal which of the following?

  1. Trisomy 13 (correct answer)
  2. Trisomy 18
  3. Trisomy 21
  4. Triploidy (69,XXY)

Explanation: This constellation of findings, including midline defects (cleft lip/palate), microcephaly, cutis aplasia, polydactyly, and micropthalmia, is classic for Patau syndrome, which is caused by Trisomy 13. Trisomy 18 presents with clenched hands and rocker-bottom feet, while Trisomy 21 has characteristic facial features and often congenital heart disease.

Question 13

A newborn female is evaluated for dysmorphic features. She has a prominent occiput, micrognathia, low-set ears, and clenched fists with overlapping fingers (index over middle, fifth over fourth). She also has rocker-bottom feet. A cardiac murmur is present, and an echocardiogram reveals a ventricular septal defect.

This infant's condition is most likely caused by which chromosomal abnormality?

  1. Trisomy 13
  2. Trisomy 18 (correct answer)
  3. Deletion of chromosome 5p
  4. Deletion of chromosome 22q11

Explanation: The clinical presentation, particularly the clenched fists with overlapping fingers, rocker-bottom feet, micrognathia, and prominent occiput, is highly characteristic of Edwards syndrome, which is caused by Trisomy 18. Trisomy 13 (Patau syndrome) has midline defects, while cri-du-chat (5p deletion) has a cat-like cry. 22q11 deletion syndrome has features like cardiac defects, abnormal facies, and hypocalcemia.

Question 14

A 2-week-old infant is brought to the pediatrician due to a high-pitched, mewing cry that sounds like a cat. The infant was born at term but was small for gestational age. Physical examination reveals microcephaly, a round face, and wide-set eyes (hypertelorism). The parents are concerned about the infant's poor feeding and weak suck.

This infant's syndrome is caused by which of the following genetic alterations?

  1. Microdeletion of chromosome 7q
  2. Terminal deletion of the short arm of chromosome 5 (correct answer)
  3. Paternal deletion of chromosome 15q
  4. Trisomy of chromosome 13

Explanation: The distinctive cat-like cry (cri du chat) is the hallmark feature of cri-du-chat syndrome. This condition is caused by a terminal or interstitial deletion of a portion of the short arm (p arm) of chromosome 5.

Question 15

A 19-year-old man presents to his primary care physician for a routine physical. He is noted to be tall and thin, with disproportionately long arms and legs. Physical examination reveals small, firm testes and gynecomastia. Laboratory studies are ordered to evaluate for suspected hypogonadism.

Which of the following sets of laboratory findings is most consistent with the underlying chromosomal disorder?

  1. Low testosterone, low LH, low FSH
  2. High testosterone, high LH, high FSH
  3. Low testosterone, high LH, high FSH (correct answer)
  4. Normal testosterone, low LH, normal FSH

Explanation: The patient's phenotype is classic for Klinefelter syndrome (47,XXY). The extra X chromosome leads to testicular dysgenesis, resulting in primary hypogonadism. The damaged Leydig cells produce insufficient testosterone (low testosterone), and the damaged seminiferous tubules produce insufficient inhibin. The lack of negative feedback from testosterone and inhibin on the pituitary and hypothalamus leads to elevated levels of both LH and FSH (hypergonadotropic hypogonadism).

Question 16

A 5-year-old girl is brought to a developmental pediatrician due to severe intellectual disability and frequent, unprovoked episodes of laughter. Her parents note she has a stiff, jerky gait and flaps her hands. She has minimal speech development. Pregnancy and birth history were unremarkable. Physical examination reveals microcephaly and a wide mouth.

This patient's condition is most likely caused by a genetic defect inherited from which parent?

  1. Maternal deletion on chromosome 15 (correct answer)
  2. Paternal deletion on chromosome 15
  3. Maternal deletion on chromosome 5
  4. Paternal deletion on chromosome 7

Explanation: The clinical presentation of inappropriate laughter, jerky movements (ataxia), seizures, and severe intellectual disability is characteristic of Angelman syndrome. This condition is caused by a loss of function of the UBE3A gene on chromosome 15. Due to genomic imprinting, the paternal copy of this gene is normally silenced in the brain. Therefore, the disease occurs when the maternal copy is deleted or mutated.

Question 17

A 4-year-old boy is evaluated for developmental delay and an insatiable appetite. He was born with severe hypotonia and had difficulty feeding as an infant. He is now obese, with small hands and feet. Genetic testing is performed and confirms a diagnosis of Prader-Willi syndrome. Further analysis reveals that the patient has two copies of the maternal chromosome 15 and no paternal chromosome 15.

Which of the following genetic mechanisms best describes the cause of this patient's condition?

  1. Maternal uniparental disomy (correct answer)
  2. Paternal uniparental disomy
  3. Microdeletion of the maternal chromosome 15
  4. An imprinting center defect on the paternal chromosome

Explanation: Prader-Willi syndrome results from the loss of function of genes on the paternal chromosome 15, which are normally expressed while the maternal copies are silenced (imprinted). While the most common cause is a paternal deletion, this patient's case is caused by maternal uniparental disomy, where both copies of chromosome 15 are inherited from the mother. With no paternal chromosome 15 present, the necessary genes are not expressed, leading to the syndrome.

Question 18

A 7-year-old boy is referred for evaluation due to learning difficulties and a cheerful, overly friendly demeanor. He is highly verbal and social with strangers. Physical examination shows a flattened nasal bridge, a long philtrum, and a wide smile with widely spaced teeth. A cardiology consultation reveals supravalvular aortic stenosis.

This patient's condition is most likely caused by a microdeletion on which of the following chromosomes?

  1. Chromosome 4
  2. Chromosome 7 (correct answer)
  3. Chromosome 17
  4. Chromosome 22

Explanation: The combination of distinctive 'elfin' facial features, an unusually friendly personality, intellectual disability, and supravalvular aortic stenosis is characteristic of Williams syndrome. This condition is caused by a microdeletion on the long arm of chromosome 7 (7q11.23), which includes the gene for elastin.

Question 19

A couple is undergoing counseling for infertility. Karyotype analysis is performed. The man's karyotype is 46,XY. The woman's karyotype is 46,X,i(Xq). She has some features of Turner syndrome, including short stature and premature ovarian failure, but lacks others, such as a webbed neck or coarctation of the aorta.

The formation of the abnormal chromosome in this woman is best explained by which of the following mechanisms?

  1. Transverse division of the centromere during meiosis (correct answer)
  2. Fusion of the ends of a chromosome after loss of telomeres
  3. Nondisjunction of homologous chromosomes
  4. Breakage and rejoining of two non-homologous chromosomes

Explanation: The notation i(Xq) indicates an isochromosome of the long arm of the X chromosome. An isochromosome is a mirror-image chromosome consisting of two copies of either the short arm (p) or the long arm (q). It forms when the centromere divides transversely (horizontally) instead of longitudinally (vertically) during meiosis II or mitosis, leading to loss of one arm and duplication of the other.

Question 20

A 17-year-old boy is evaluated for behavioral issues and severe cystic acne. He is noted to be very tall for his family, at the 98th percentile for height. He has a history of learning disabilities and has been diagnosed with an impulse control disorder. His parents have normal karyotypes.

This patient's condition most likely resulted from a nondisjunction event during which of the following processes?

  1. Maternal meiosis I
  2. Maternal meiosis II
  3. Paternal meiosis I
  4. Paternal meiosis II (correct answer)

Explanation: The patient's presentation of tall stature, severe acne, and behavioral problems suggests a 47,XYY karyotype. This aneuploidy results from the fertilization of a normal ovum (X) by a sperm carrying two Y chromosomes (YY). A YY sperm is formed as a result of nondisjunction of the sister chromatids of the Y chromosome during paternal meiosis II.