Mod. 1 Genetic and Congenital Alterations Flashcards
Which of the following hallmark manifestations would be observed in a physical exam of a patient with Marfan syndrome?
A) Glaucoma
B) Inguinal hernia
C) Lens displacement
D) Mitral regurgitation
C) Lens displacement
Rationale: Marfan syndrome is a connective tissue disorder affecting the eyes, skeletal system, and cardiovascular system. Lens displacement (ectopia lentis) is a hallmark manifestation due to weakened zonular fibers.
Type 1 neurofibromatosis (NF1) results from a mutation on chromosome 17 affecting which tumor-suppressing protein?
A) Merlin
B) Albumin
C) Fibrillin-1
D) Neurofibromin
D) NeurofibrominRationale: NF1 gene mutations impair neurofibromin, a protein crucial for tumor suppression. Its dysfunction leads to excessive cell proliferation, forming neurofibromas.
Which of the following is a hallmark feature of Tay-Sachs disease?
A) Gradual improvement in neurological function
B) Presence of a cherry-red macula on retinal examination
C) Increased levels of phenylalanine in the blood
D) Defective neurofibromin production
B) Presence of a cherry-red macula on retinal examination
Rationale: Tay-Sachs disease is caused by a mutation in the HEXA gene, leading to hexosaminidase A deficiency. This results in lipid accumulation in neurons, with a cherry-red macula seen on eye examination.
True or False: Fragile X syndrome is generally more severe in males than females.
Answer: True
Rationale: Males only have one X chromosome, so the full mutation of FMR1 leads to more severe cognitive and behavioral impairments compared to females, who have a second X chromosome that may compensate.
Which of the following correctly describes phenylketonuria (PKU)?
A) X-linked disorder
B) Autosomal dominant disorder
C) Autosomal recessive disorder
D) Chromosomal disorder
C) Autosomal recessive disorderRationale: PKU is an autosomal recessive metabolic disorder caused by a deficiency of phenylalanine hydroxylase, leading to an inability to convert phenylalanine into tyrosine.
A newborn is diagnosed with Klinefelter syndrome (XXY). Which of the following findings would be expected?
A) Short stature and webbed neck
B) Simian crease and intellectual disability
C) Gynecomastia and sparse body hair
D) Horseshoe kidney and coarctation of the aorta
C) Gynecomastia and sparse body hair
Rationale: Klinefelter syndrome (47, XXY) presents with small testes, gynecomastia, sparse facial/body hair, and long limbs with a short trunk.
What is the primary cause of developmental delays in Down syndrome?
A) Trisomy 18
B) Single-gene mutation
C) Trisomy 21
D) X-linked mutation
C) Trisomy 21
Rationale: Down syndrome results from a trisomy of chromosome 21, leading to developmental delays, intellectual disability, and characteristic facial features.
Which of the following statements about Turner syndrome is correct?
A) It affects only males and is caused by an extra Y chromosome.
B) It results from a deletion or absence of one X chromosome in females.
C) Affected individuals present with gynecomastia and infertility.
D) It is an autosomal recessive disorder with intellectual disability.
B) It results from a deletion or absence of one X chromosome in females.
Rationale: Turner syndrome (45, X) is a chromosomal disorder affecting females, characterized by short stature, gonadal dysgenesis, and webbed neck.
Which of the following congenital disorders is considered multifactorial rather than single-gene or chromosomal?
A) Duchenne muscular dystrophy
B) Huntington’s disease
C) Cleft lip and palate
D) Cystic fibrosis
C) Cleft lip and palate
Rationale: Cleft lip and palate result from an interaction of genetic and environmental factors, making it a multifactorial disorder.
What is the primary diagnostic test for Down syndrome during pregnancy?
A) Amniocentesis
B) Serum phenylalanine test
C) HEXA enzyme activity test
D) X-linked gene sequencing
A) Amniocentesis
Rationale: Amniocentesis is used to analyze fetal chromosomes, making it the gold standard for prenatal Down syndrome diagnosis.
A 15-year-old female presents to the clinic with short stature, webbed neck, widely spaced nipples, and delayed puberty. She has a history of recurrent ear infections and was found to have coarctation of the aorta on echocardiogram. Based on these findings, which of the following diagnostic tests would confirm the suspected diagnosis?
A) Serum estrogen and FSH levels
B) Karyotyping
C) Skeletal X-ray
D) Bone marrow biopsy
B) Karyotyping
Rationale: Turner syndrome results from the complete or partial absence of one X chromosome (45, X). Karyotyping confirms the diagnosis. Patients typically present with short stature, webbed neck, cardiovascular anomalies (e.g., coarctation of the aorta), and ovarian dysgenesis, leading to delayed puberty and infertility.
A 22-year-old male visits a fertility clinic due to difficulty conceiving with his partner. On physical exam, he has tall stature, long limbs, sparse facial and body hair, gynecomastia, and small, firm testes. Laboratory findings reveal decreased testosterone and increased FSH and LH levels. What is the most likely underlying diagnosis?
A) Fragile X syndrome
B) Klinefelter syndrome
C) Turner syndrome
D) Marfan syndrome
B) Klinefelter syndrome
Rationale: Klinefelter syndrome (47, XXY) is a sex chromosome aneuploidy characterized by hypogonadism, tall stature, gynecomastia, and infertility. The hallmark is testicular atrophy, leading to decreased testosterone and increased gonadotropins (FSH, LH). Diagnosis is confirmed by karyotyping.
A 17-year-old male presents to the emergency department after a sudden onset of severe chest pain radiating to the back. He is tall and thin, with long fingers and hypermobile joints. An aortic murmur is noted on auscultation. Which of the following is the most likely life-threatening complication?
A) Pulmonary embolism
B) Myocardial infarction
C) Aortic dissection
D) Cardiac tamponade
C) Aortic dissection
Rationale: Marfan syndrome is an autosomal dominant disorder affecting connective tissue due to a mutation in the FBN1 gene on chromosome 15. It is associated with skeletal abnormalities, lens dislocation, and cardiovascular complications, particularly aortic root dilation, which can lead to life-threatening aortic dissection.
A pregnant woman at 14 weeks gestation undergoes a prenatal screening test, which reveals an increased nuchal translucency and low maternal serum alpha-fetoprotein (AFP). Which additional finding is most likely to be seen on a fetal ultrasound?
A) Horseshoe kidney
B) Congenital heart defect
C) Hypertonia
D) Hypoplastic nasal bone
D) Hypoplastic nasal bone
Rationale: Trisomy 21 (Down syndrome) is characterized by specific ultrasound markers, including increased nuchal translucency, hypoplastic nasal bone, and congenital heart defects (e.g., atrioventricular septal defect). Maternal serum screening often shows decreased AFP and increased beta-hCG.
A 4-year-old boy is brought to the pediatrician due to delayed speech and hyperactivity. His mother reports that he frequently bites his hands when frustrated. On physical exam, he has a long face, large ears, and a prominent jaw. His older brother has a similar condition. Genetic testing reveals an increased number of CGG trinucleotide repeats on the FMR1 gene. Which of the following best describes the inheritance pattern of this disorder?
A) Autosomal dominant
B) Autosomal recessive
C) X-linked dominant
D) X-linked recessive
C) X-linked dominant
Rationale: Fragile X syndrome is caused by an expansion of CGG trinucleotide repeats in the FMR1 gene on the X chromosome, leading to intellectual disability and autistic behaviors. It follows an X-linked dominant inheritance pattern, with males more severely affected due to having only one X chromosome.
A 6-year-old child presents with multiple café-au-lait spots, axillary freckling, and soft, non-tender nodules on the skin. Ophthalmologic exam reveals Lisch nodules (pigmented iris hamartomas). What is the most likely diagnosis?
A) Trisomy 21
B) Neurofibromatosis type 1
C) Turner syndrome
D) Fragile X syndrome
B) Neurofibromatosis type 1
Rationale: NF1 is caused by a mutation in the NF1 gene on chromosome 17, leading to decreased tumor suppression and uncontrolled nerve tissue growth. Classic findings include café-au-lait spots, axillary freckling, Lisch nodules, and neurofibromas.
Treatment: Symptom management, surgical removal of neurofibromas if needed, and monitoring for malignant transformation.
A 14-year-old male presents with tall stature, long limbs, pectus excavatum, and hypermobile joints. He also has aortic root dilation on echocardiogram. What is the most likely diagnosis?
A) Marfan syndrome
B) Turner syndrome
C) Fragile X syndrome
D) Klinefelter syndrome
A) Marfan syndrome
Rationale: Marfan syndrome is an autosomal dominant disorder caused by mutations in the FBN1 gene, affecting connective tissue. Patients often present with tall stature, long limbs, pectus deformities, hypermobility, and cardiovascular complications like aortic root dilation.
Treatment: Beta-blockers, lifestyle modifications to reduce cardiovascular strain, and surgical intervention if aortic dilation progresses.
A newborn presents with hypotonia, upward-slanting palpebral fissures, a single transverse palmar crease, and a congenital heart defect. The mother was 42 years old at the time of delivery. Which genetic abnormality is most likely responsible?
A) 47,XXY
B) 45,X
C) Trisomy 21
D) 46,XY with FMR1 expansion
C) Trisomy 21
Rationale: Down syndrome (Trisomy 21) presents with hypotonia, distinct facial features, Simian crease, and congenital heart defects. Maternal age >35 increases the risk of nondisjunction leading to Trisomy 21.
Treatment: Supportive care, early intervention programs, and monitoring for congenital heart disease, thyroid disorders, and developmental delays.
A 25-year-old male presents with tall stature, gynecomastia, small testes, and sparse facial hair. He reports difficulty with learning and social interactions. Genetic testing confirms the presence of an extra X chromosome. What is the most likely diagnosis?
A) Fragile X syndrome
B) Klinefelter syndrome
C) Turner syndrome
D) Marfan syndrome
B) Klinefelter syndrome
Rationale: Klinefelter syndrome (47,XXY) occurs due to an extra X chromosome in males. It presents with tall stature, gynecomastia, small testes, and learning difficulties.
Treatment: Testosterone replacement therapy, fertility treatments if needed, and speech/educational support.
A 16-year-old female presents with short stature, widely spaced nipples, a webbed neck, and primary amenorrhea. Physical exam reveals coarctation of the aorta. What is the most likely diagnosis?
A) Trisomy 21
B) Turner syndrome
C) Klinefelter syndrome
D) Marfan syndrome
B) Turner syndrome
Rationale: Turner syndrome (45,X) occurs due to complete or partial loss of an X chromosome. It affects only females and presents with short stature, broad chest, webbed neck, and congenital heart defects like coarctation of the aorta.
Treatment: Growth hormone therapy, estrogen replacement therapy, and management of cardiac and renal anomalies.
A 3-year-old male presents with developmental delays, impulsive behavior, and a long face with large ears and a prominent jaw. Genetic testing reveals over 200 CGG repeats on the FMR1 gene of the X chromosome. Which of the following is the most likely diagnosis?
A) Klinefelter syndrome
B) Turner syndrome
C) Fragile X syndrome
D) Marfan syndrome
C) Fragile X syndrome
Rationale: Fragile X syndrome is caused by a trinucleotide repeat expansion (>200 CGG repeats) in the FMR1 gene, affecting synaptic development. It is more severe in males due to having only one X chromosome.
Treatment: Behavioral therapy, special education programs, speech therapy, and medications for ADHD or anxiety.
