Genetic Flashcards
(54 cards)
A 2-year-old boy presents with hypotonia, hyperphagia, obesity, short stature, and hypogonadism. Which of the following best explains the genetic mechanism of his disorder?
a) Maternal deletion on chromosome 15q11-q13
b) Paternal deletion on chromosome 15q11-q13
c) Trisomy 15
d) Uniparental isodisomy of paternal chromosome 15
Correct Answer: B
The child’s presentation—marked by hypotonia, hyperphagia, obesity, short stature, and hypogonadism—is characteristic of Prader-Willi syndrome. This disorder results from the absence of paternally expressed genes in the chromosome 15q11–q13 region. The most common cause (~70%) is a deletion on the paternal chromosome. Other mechanisms include maternal uniparental disomy (where both chromosome 15s are inherited from the mother) and imprinting defects. It is important to note that maternal deletion in this region leads to Angelman syndrome, not Prader-Willi syndrome. Trisomy 15 and paternal uniparental disomy are not typically associated with this presentation.
A newborn is noted to have micrognathia, cleft palate, glossoptosis (tongue falls backward), and respiratory distress.
Which of the following syndromes is most likely?
a) Treacher Collins syndrome
b) Pierre Robin sequence
c) DiGeorge syndrome
d) Beckwith-Wiedemann syndrome
Correct Answer: b
Pierre Robin sequence is characterized by a triad of micrognathia (small jaw), glossoptosis (posterior displacement of the tongue), and cleft palate. These features can lead to airway obstruction and feeding difficulties. It is considered a ‘sequence’ because one anomaly (micrognathia) leads to the subsequent problems during embryologic development. It may occur in isolation or be associated with syndromes like Stickler syndrome. Treacher Collins syndrome includes facial dysmorphism but also has ear anomalies and zygomatic hypoplasia. DiGeorge syndrome involves cardiac defects, thymic hypoplasia, and hypocalcemia. Beckwith-Wiedemann syndrome is associated with macroglossia, organomegaly, and an increased risk of tumors, not glossoptosis or cleft palate.
A newborn presents with hypotonia, poor feeding, upslanting palpebral fissures, a single transverse palmar crease, and a protruding tongue.
Which of the following is the most likely underlying chromosomal abnormality?
a) Trisomy 13
b) Trisomy 18
c) Trisomy 21
d) Monosomy X
Correct Answer: c
The described features—hypotonia, poor feeding, upslanting palpebral fissures, single palmar crease, and protruding tongue—are classic signs of Down syndrome, which is caused by trisomy 21. This is the most common chromosomal abnormality in live-born infants. Trisomy 13 (Patau syndrome) and Trisomy 18 (Edwards syndrome) also present with dysmorphic features but are associated with more severe malformations and a high early mortality. Monosomy X (Turner syndrome) occurs only in females and presents with short stature, webbed neck, and lymphedema.
A 14-year-old girl presents with short stature, primary amenorrhea, and a webbed neck. On examination, she has a broad chest with widely spaced nipples.
Which of the following is the most likely karyotype?
a) 45,X
b) 47,XXY
c) 46,XX
d) 47,XXX
Correct Answer: a
The clinical features described—short stature, primary amenorrhea, webbed neck, and broad chest—are characteristic of Turner syndrome, which is caused by monosomy X (45,X). This is a sex chromosome aneuploidy affecting females. Other features may include lymphedema, low hairline, and cardiac anomalies like coarctation of the aorta. 47,XXY describes Klinefelter syndrome, which affects males and presents with tall stature and small testes. 46,XX is a normal female karyotype, and 47,XXX females are often phenotypically normal or have only mild symptoms.
A child is diagnosed with cystic fibrosis. Genetic testing shows a mutation in the CFTR gene. What is the most likely mode of inheritance for this condition?
a) Autosomal dominant
b) Autosomal recessive
c) X-linked recessive
d) Mitochondrial
Correct Answer: b
Cystic fibrosis is inherited in an autosomal recessive manner. It is caused by mutations in the CFTR gene located on chromosome 7. Affected individuals inherit one defective allele from each parent. The most common mutation is ΔF508. Carriers (heterozygotes) are typically asymptomatic. Autosomal dominant inheritance is seen in conditions like Marfan syndrome, while X-linked recessive disorders include hemophilia A and Duchenne muscular dystrophy. Mitochondrial inheritance involves genes transmitted only through the maternal line.
A child is born with macrosomia, macroglossia, and omphalocele. Genetic testing reveals alterations in the 11p15 region.
Which of the following conditions is most likely?
a) Angelman syndrome
b) Beckwith-Wiedemann syndrome
c) Prader-Willi syndrome
d) DiGeorge syndrome
Correct Answer: b
Beckwith-Wiedemann syndrome (BWS) is characterized by macrosomia (large body size), macroglossia (large tongue), and abdominal wall defects such as omphalocele or umbilical hernia. It is associated with dysregulation of imprinted genes on chromosome 11p15. Children with BWS also have an increased risk of embryonal tumors, such as Wilms tumor and hepatoblastoma. Angelman and Prader-Willi syndromes are both related to chromosome 15q11–q13 but present with very different features. DiGeorge syndrome involves 22q11 deletion and features cardiac defects, thymic hypoplasia, and hypocalcemia, not overgrowth or omphalocele.
A 2-year-old boy presents with speech delay, ataxia, inappropriate laughter (happy puppet appearance), and seizures. Genetic analysis shows maternal deletion on chromosome 15q11–q13.
What is the most likely diagnosis?
a) Rett syndrome
b) Fragile X syndrome
c) Angelman syndrome
d) Prader-Willi syndrome
Correct Answer: c
Angelman syndrome is caused by the loss of function of the maternally inherited genes in the 15q11–q13 region. Clinical features include developmental delay, speech impairment, ataxia, seizures, and a characteristic ‘happy puppet’ appearance with frequent inappropriate laughter. In contrast, Prader-Willi syndrome involves paternal deletion in the same region and presents with hypotonia, obesity, and hypogonadism. Fragile X syndrome is the most common inherited cause of intellectual disability and includes macroorchidism and long face. Rett syndrome is an X-linked dominant disorder typically affecting girls, associated with regression, loss of purposeful hand use, and stereotypic hand movements.
A 5-year-old boy presents with long face, large ears, intellectual disability, and macroorchidism. He has a family history of similar findings in male relatives.
Which of the following is the most likely diagnosis?
a) Klinefelter syndrome
b) Fragile X syndrome
c) Angelman syndrome
d) Marfan syndrome
Correct Answer: b
Fragile X syndrome is the most common inherited cause of intellectual disability. It is caused by a CGG trinucleotide repeat expansion in the FMR1 gene on the X chromosome. Key features include a long face, large ears, macroorchidism (especially after puberty), and behavioral problems such as ADHD and autistic features. It follows an X-linked dominant pattern with variable expression, more severe in males. Klinefelter syndrome (47,XXY) presents with tall stature, small testes, and gynecomastia. Marfan syndrome affects connective tissue and is associated with long limbs, aortic root dilation, and lens dislocation. Angelman syndrome involves severe intellectual disability with ataxia and happy demeanor but not macroorchidism or family history in males.
A newborn with cleft lip and palate, polydactyly, microphthalmia, and holoprosencephaly is diagnosed shortly after birth.
What is the most likely chromosomal abnormality?
a) Trisomy 13
b) Trisomy 18
c) Trisomy 21
d) 45,X
Correct Answer: a
The clinical features described—cleft lip and palate, polydactyly, microphthalmia, and holoprosencephaly—are classic signs of Trisomy 13, also known as Patau syndrome. It is a severe chromosomal disorder often leading to death within the first year of life. Trisomy 18 (Edwards syndrome) presents with clenched fists, rocker-bottom feet, and cardiac anomalies. Trisomy 21 (Down syndrome) is associated with hypotonia, upslanting palpebral fissures, and a single palmar crease. 45,X (Turner syndrome) affects females and is characterized by short stature, webbed neck, and gonadal dysgenesis, not midline defects like holoprosencephaly.
A couple with one child affected by an autosomal recessive disorder wants to know the recurrence risk for future children. What is the chance that their next child will also be affected?
a) 0%
b) 25%
c) 50%
d) 100%
Correct Answer: b
In autosomal recessive inheritance, both parents are typically carriers (heterozygous). With each pregnancy, there is a 25% chance the child will be affected (inherits both mutant alleles), a 50% chance the child will be a carrier (inherits one mutant allele), and a 25% chance the child will inherit two normal alleles. Therefore, the recurrence risk for an affected child is 25% in each pregnancy, regardless of previous outcomes.
A neonate is diagnosed with DiGeorge syndrome. Which of the following findings is NOT commonly associated with this condition?
a) Hypocalcemia
b) Conotruncal heart defects
c) Immunodeficiency due to thymic hypoplasia
d) Macroglossia
Correct Answer: d
DiGeorge syndrome (22q11.2 deletion syndrome) typically presents with hypocalcemia (due to parathyroid hypoplasia), conotruncal heart defects (e.g., tetralogy of Fallot, truncus arteriosus), and immunodeficiency due to thymic hypoplasia or aplasia. Macroglossia is not a feature of DiGeorge syndrome—it is a characteristic finding in Beckwith-Wiedemann syndrome. Other features of DiGeorge may include facial dysmorphism, cleft palate, developmental delay, and psychiatric disorders in later life.
Which of the following genetic testing methods is best suited for detecting microdeletions such as 22q11.2 in DiGeorge syndrome?
a) Karyotyping
b) Fluorescence in situ hybridization (FISH)
c) Polymerase chain reaction (PCR)
d) Whole-exome sequencing
Correct Answer: b
FISH (Fluorescence In Situ Hybridization) is the preferred method for detecting specific microdeletions, such as the 22q11.2 deletion in DiGeorge syndrome. It uses fluorescent probes that bind to specific DNA sequences, allowing direct visualization of the deletion under a microscope. Karyotyping detects larger chromosomal abnormalities (>5 Mb) but often misses microdeletions. PCR is useful for detecting known small mutations or repeat expansions, not for structural deletions. Whole-exome sequencing focuses on coding regions but may miss structural variations unless paired with copy number analysis.
A newborn girl has hypotonia, high forehead, long philtrum, thin upper lip, and a smooth philtrum. Mother consumed alcohol heavily during pregnancy.
What is the most likely diagnosis?
a) Smith-Lemli-Opitz syndrome
b) Fetal alcohol syndrome
c) Cornelia de Lange syndrome
d) Williams syndrome
Correct Answer: b
Fetal alcohol syndrome (FAS) is caused by prenatal alcohol exposure and is characterized by facial dysmorphism (smooth philtrum, thin upper lip, short palpebral fissures), growth restriction, and central nervous system abnormalities such as microcephaly, intellectual disability, and hypotonia. It is one of the most common preventable causes of intellectual disability. Smith-Lemli-Opitz syndrome involves cholesterol biosynthesis defects. Cornelia de Lange presents with limb anomalies and synophrys (unibrow). Williams syndrome features elfin facies and hypercalcemia.
Which of the following inheritance patterns is most consistent with a disorder affecting only males, transmitted from carrier mothers, and skipping generations?
a) Autosomal dominant
b) Autosomal recessive
c) X-linked recessive
d) Mitochondrial
Correct Answer: c
X-linked recessive inheritance typically affects males more than females because males have only one X chromosome. Carrier mothers (heterozygous) can transmit the mutated gene to 50% of their sons, who will be affected. The disorder often appears to ‘skip generations’ through carrier females. Examples include hemophilia A, Duchenne muscular dystrophy, and red-green color blindness. Autosomal dominant and recessive patterns affect both sexes equally, and mitochondrial inheritance is exclusively maternal.
A child with intellectual disability has a deletion on chromosome 7q11.23. He exhibits a friendly personality, supravalvular aortic stenosis, and elfin facies.
What is the most likely diagnosis?
a) Noonan syndrome
b) Williams syndrome
c) Smith-Magenis syndrome
d) Cornelia de Lange syndrome
Correct Answer: b
Williams syndrome is caused by a microdeletion at chromosome 7q11.23. It is characterized by intellectual disability, distinctive ‘elfin’ facial features, a gregarious personality, and cardiovascular abnormalities, most notably supravalvular aortic stenosis. Noonan syndrome involves short stature, webbed neck, and pulmonary stenosis. Smith-Magenis syndrome involves self-injurious behavior, sleep disturbance, and intellectual disability. Cornelia de Lange syndrome includes growth retardation, limb abnormalities, and synophrys.
A 3-year-old girl presents with developmental delay, seizures, and hand-wringing movements. She had normal development until 6 months of age.
Which of the following is the most likely diagnosis?
a) Rett syndrome
b) Fragile X syndrome
c) Angelman syndrome
d) Tuberous sclerosis
Correct Answer: a
Rett syndrome is a neurodevelopmental disorder that primarily affects girls and is caused by mutations in the MECP2 gene on the X chromosome. It typically presents after a period of normal early development followed by regression, loss of purposeful hand skills, development of stereotypic hand movements (hand-wringing), seizures, and intellectual disability. Fragile X syndrome has more consistent delays from early life. Angelman syndrome is also associated with seizures and a happy demeanor, but not regression or hand-wringing. Tuberous sclerosis involves hypopigmented macules, facial angiofibromas, and hamartomas, along with seizures.
A male infant presents with fair skin, blue eyes, intellectual disability, and a musty odor. Which of the following metabolic disorders is most likely?
a) Maple syrup urine disease
b) Homocystinuria
c) Phenylketonuria
d) Tyrosinemia type I
Correct Answer: c
Phenylketonuria (PKU) is an autosomal recessive disorder caused by deficiency of phenylalanine hydroxylase, leading to accumulation of phenylalanine. Clinical features include intellectual disability, hypopigmentation (fair skin, light hair, blue eyes), eczema, and a characteristic musty or mousy body odor. Early diagnosis via newborn screening and dietary management can prevent neurologic damage. Maple syrup urine disease presents with sweet-smelling urine and encephalopathy. Homocystinuria is associated with Marfanoid habitus and thromboembolic risk. Tyrosinemia type I typically presents with liver failure and a cabbage-like odor.
A newborn presents with hypotonia, feeding difficulties, and a high-pitched cat-like cry. Genetic testing reveals a deletion on chromosome 5p.
Which of the following syndromes is most likely?
a) Cri-du-chat syndrome
b) Smith-Magenis syndrome
c) Prader-Willi syndrome
d) Williams syndrome
Correct Answer: a
Cri-du-chat syndrome (5p deletion syndrome) is caused by a deletion on the short arm of chromosome 5. It presents with a high-pitched, cat-like cry, hypotonia, microcephaly, intellectual disability, and distinctive facial features. Smith-Magenis syndrome involves a deletion on chromosome 17p11.2 and is associated with sleep disturbances and behavioral problems. Prader-Willi syndrome involves chromosome 15q11–q13 with hypotonia and hyperphagia, but not the cat-like cry. Williams syndrome involves chromosome 7q11.23 and is characterized by elfin facies and cardiovascular anomalies.
A 7-year-old boy presents with progressive muscle weakness, calf pseudohypertrophy, and Gowers’ sign. His maternal uncle had similar symptoms and died in his teens.
Which of the following best explains the inheritance pattern of this condition?
a) Autosomal dominant
b) Autosomal recessive
c) X-linked recessive
d) Mitochondrial
Correct Answer: c
The clinical presentation is consistent with Duchenne muscular dystrophy (DMD), a severe X-linked recessive disorder caused by mutations in the dystrophin gene. It affects males, and carrier females can pass the mutation to their sons. Key signs include Gowers’ sign (use of hands to rise from the floor), progressive proximal muscle weakness, and calf pseudohypertrophy. Autosomal dominant or recessive inheritance would affect both sexes equally, and mitochondrial inheritance is maternal and affects all children of affected mothers.
A 6-year-old girl presents with short stature, webbed neck, widely spaced nipples, and lymphedema of the hands and feet. Which of the following additional features is most commonly associated with her likely diagnosis?
a) Renal agenesis
b) Coarctation of the aorta
c) Polycystic kidney disease
d) Ventricular septal defect
Correct Answer: b
The described features are classic for Turner syndrome (45,X), which presents with short stature, webbed neck, lymphedema, and widely spaced nipples. One of the most common associated cardiovascular anomalies is coarctation of the aorta. Other common features include bicuspid aortic valve and horseshoe kidney. Renal agenesis and polycystic kidney disease are not typical. VSDs are more common in trisomies such as Down syndrome.
A newborn with ambiguous genitalia has 46,XX karyotype, elevated 17-hydroxyprogesterone, and salt-wasting crisis. Which of the following enzyme deficiencies is most likely?
a) 11β-hydroxylase deficiency
b) 17α-hydroxylase deficiency
c) 21-hydroxylase deficiency
d) Aromatase deficiency
Correct Answer: c
21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia (CAH). It results in cortisol and aldosterone deficiency with excess androgen production. In 46,XX infants, it causes virilization of the external genitalia (ambiguous genitalia). The salt-wasting form presents with life-threatening hyponatremia, hyperkalemia, and hypovolemia. Elevated 17-hydroxyprogesterone is a key diagnostic marker. 11β-hydroxylase deficiency can also cause virilization but leads to hypertension. 17α-hydroxylase deficiency leads to sexual infantilism and hypertension. Aromatase deficiency affects estrogen synthesis and maternal virilization during pregnancy.
A newborn presents with hypotonia, poor feeding, and weak cry. Genetic testing confirms spinal muscular atrophy (SMA) type 1. Which gene is most commonly mutated in this condition?
a) DMD
b) SMN1
c) MECP2
d) FMR1
Correct Answer: b
Spinal muscular atrophy (SMA) type 1 is caused by mutations or deletions in the SMN1 (Survival Motor Neuron 1) gene. It is an autosomal recessive neuromuscular disorder and the most severe form of SMA, characterized by profound hypotonia, tongue fasciculations, and progressive muscle weakness from infancy. DMD is associated with Duchenne muscular dystrophy, MECP2 is mutated in Rett syndrome, and FMR1 is the gene responsible for Fragile X syndrome.
A couple has a child with cleft lip and palate. There is no family history. They ask about recurrence risk in the next child.
Which of the following statements is most accurate?
a) Risk is negligible unless both parents are carriers
b) Risk is higher if a sibling is affected
c) Risk is always 50% due to dominant inheritance
d) Cleft lip is always syndromic
Correct Answer: b
Cleft lip and palate are often multifactorial in origin, involving both genetic and environmental factors. When one child is affected, the recurrence risk in subsequent children is higher compared to the general population. If multiple siblings or a parent is affected, the risk increases further. It does not follow a simple Mendelian pattern unless it is part of a syndrome. Not all cases are syndromic—most are isolated. Therefore, the risk is not always 50% or negligible but depends on family history and severity.
A female neonate has ambiguous genitalia, normal internal female organs, and hypertension. Labs show low renin and low aldosterone.
Which enzyme deficiency is most likely?
a) 21-hydroxylase deficiency
b) 11β-hydroxylase deficiency
c) 17α-hydroxylase deficiency
d) Aromatase deficiency
Correct Answer: b
11β-hydroxylase deficiency is a form of congenital adrenal hyperplasia that leads to excess androgen production (causing virilization in 46,XX individuals) and accumulation of 11-deoxycorticosterone, a mineralocorticoid that causes hypertension, low renin, and low aldosterone. 21-hydroxylase deficiency causes virilization but is usually associated with hypotension and salt-wasting. 17α-hydroxylase deficiency causes under-virilization and hypertension, but not ambiguous genitalia in females. Aromatase deficiency leads to maternal virilization and affects estrogen synthesis.
