Medical Genetics - V. M. Zaporozhan 2005

Monogenic Disorders
Review Questions for Chapter 6

1. Etiology AND Pathogenesis of monogenic disorders, population frequency.

2. Classification of monogenic diseases and syndromes. Genetic heterogeneity.

3. Clinical Features of monogenic disorders.

4. V. McKusick's catalog of genes and Genetic Disorders.

5. Monogenic diseases and syndromes with Autosomal dominant inheritance: Achondroplasia, Marfan Syndrome, acrocephalosyndactyly (Apert syndrome), Ehlers-Danlos syndrome. Clinical presentation, Diagnosis, patient management and Treatment, prenatal diagnosis, MEDICAL Genetic Counseling, genetic risk assessment.

6. Monogenic diseases and syndromes with Autosomal Recessive Inheritance: phenylketonuria, cystic fibrosis, galactosemia, hypothyroidism, adrenogenital syndrome.

7. Inherited Metabolic Disorders and their classification. Symptoms indicating an inherited metabolic disorder.

8. What are storage diseases? Glycogen Storage Diseases. Mucopolysaccharidoses. Sphingolipidoses.

9. What are peroxisomal disorders?

10. Monogenic diseases and syndromes with X-linked inheritance: Duchenne-Becker muscular dystrophy, fragile X syndrome, vitamin D-resistant Rickets (Phosphate Diabetes), hemophilia, anhidrotic ectodermal Dysplasia.

11. Examples of Mitochondrial Diseases. Inheritance patterns.

12. Diagnosis of Monogenic Disorders. Biochemical Methods. Selective and mass screening.

13. Prenatal Diagnosis of Monogenic Disorders. Principles of medical genetic counseling. Detection of heterozygous carriers of recessive pathogenic genes.

14. Principles of Treatment for Monogenic Disorders: symptomatic, pathogenetic, and etiological.

Self-assessment and study questions

Task 1

Choose one answer.

1. Which of the following is a storage disease?

A. Phenylketonuria

B. Cystic fibrosis

C. Hypothyroidism

D. Mucopolysaccharidosis

E. Adrenogenital syndrome

2. A healthy young couple, whose first child was born with cystic fibrosis, consulted a medical genetics center. What is the geneticist's most likely Conclusion regarding the recurrence risk of having another affected child?

A. Virtually 0%, as this is the result of a de novo mutation

B. 25 %

C. 50 %

D. 50 % of all sons

E. About 100 %

3. Name the type of inheritance of cystic fibrosis:

A. Autosomal recessive

B. Autosomal dominant

C. X-linked recessive

D. X-linked dominant

E. Multifactorial

4. Symptoms that should raise suspicion of enzymopathy in a patient include all of the following, except:

A. A history of unexplained early childhood deaths

B. Delayed psychomotor development

C. Unusual color or odor of urine and sweat

D. Congenital Heart defects

E. Hepatomegaly

5. Clinical manifestations appear from the first weeks of life in:

A. Phenylketonuria

B. Galactosemia.

C. Mucopolysaccharidosis

D. Sphingolipidosis

E. Wilson's disease

6. Phenylketonuria (PKU) is an inherited Amino acid METABOLISM disorder. Which statement is true for this condition?

A. PKU is an autosomal dominant disorder

B. Characteristic hyperpigmentation

C. Early dietary intervention (within the first month of life) helps prevent mental retardation

D. Congenital Malformations are frequently observed

E. Symptoms of the disease appear During the first day after birth

7. A 15-year-old boy presents with a "bird-like" face, high "gothic" palate, Pectus excavatum, joint hypermobility, and increased urinary excretion of hydroxyproline and glycosaminoglycans. What is your diagnosis?

A. Achondroplasia

B. Mucopolysaccharidosis

C. Klinefelter syndrome

D. Marfan syndrome

E. Edwards syndrome

8. A 12-year-old girl exhibits dwarfism due to shortening of the proximal segments of the limbs, isodactyly, lumbar lordosis, and Varus deformity of the lower extremities. This symptom complex is characteristic of:

A. Achondroplasia

B. Ectrodactyly

C. Down syndrome

D. Turner syndrome

E. Adrenogenital syndrome

9. A newborn girl presents with Hermaphroditism (clitoral hypertrophy), vomiting, dehydration, hyperkalemia, and hyponatremia. Which hereditary disorder is characterized by such a symptom complex?

A. Achondroplasia

B. Ectrodactyly

C. Down syndrome

D. Turner syndrome

E. Adrenogenital syndrome

10. A family consults a medical genetics center regarding mental retardation in their two sons. The family also has two healthy daughters. The boys have elongated faces, macrotia, and macroorhidism. What is the most likely diagnosis?

A. Phenylketonuria

B. Down syndrome

C. Klinefelter syndrome

D. Fragile X syndrome

E. Marfan syndrome

11. A 14-year-old boy presents with hypotrichosis, oligodontia, peg-shaped Teeth, dry Skin, and palmoplantar hyperkeratosis. This phenotype is characteristic of:

A. Fragile X syndrome

B. Duchenne muscular dystrophy

C. Anhidrotic ectodermal dysplasia

D. Phenylketonuria

E. Cystic fibrosis

12. Progressive virilization, accelerated somatic development, and elevated adrenal cortex hormone levels are characteristic of:

A. Cystic fibrosis

B. Adrenogenital syndrome

C. Klinefelter syndrome

D. Marfan syndrome

E. Acrocephalosyndactyly

13. Coarse facial features, kyphoscoliosis, sternal deformity, joint stiffness, cataract, and increased urinary excretion of glycosaminoglycans are characteristic of:

A. Mucopolysaccharidosis

B. Achondroplasia

C. Fragile X syndrome

D. Phenylketonuria

E. Neurofibromatosis

14. A man presents with Infertility and azoospermia. Which monogenic disorder may present with such symptoms?

A. Phenylketonuria

B. Cystic fibrosis

C. Mucopolysaccharidosis

D. Duchenne muscular dystrophy

E. Glycogen storage diseases

15. A child presents with recurrent Pneumonia, voluminous foul-smelling stools, and growth failure. This symptom complex is characteristic of:

A. Phenylketonuria

B. Cystic fibrosis

C. Hypothyroidism

D. Adrenogenital syndrome

E. Marfan syndrome

16. The diagnosis of Duchenne muscular dystrophy is established on The basis of:

A. Determination of Na and Cl ion concentration in sweat

B. Characteristic neurological symptoms and determination of serum creatine phosphokinase levels

C. Results of histological examination

D. Characteristic phenotype and determination of glycosaminoglycan levels in the patient's urine

E. Genealogical study and Determination of Amino acid concentrations in the patient's urine and Blood

17. A 9-month-old blue-eyed, fair-haired infant presents with a musty odor of urine and sweat, and delayed psychomotor development. Which of the following is most characteristic of this condition?

A. High chloride concentration in sweat

B. High hydroxyproline concentration in urine

C. High glycosaminoglycan concentration

D. Positive ferric chloride test

E. Reducing substances in urine

18. The urine of patients with phenylketonuria has the odor of:

A. Boiled ROOT vegetables

B. Maple syrup

C. Musty

D. Acetone

E. Sauerkraut

19. A 14-year-old boy presents with tall stature, asthenic build, joint hypermobility, pectus excavatum, Spontaneous pneumothorax, and increased urinary excretion of hydroxyproline and glycosaminoglycans. His karyotype is 46,XY. What is your diagnosis?

A. Galactosemia

B. Phenylketonuria

C. Cystic fibrosis

D. Marfan syndrome

E. Klinefelter syndrome

20. An indication for biochemical genetic testing is:

A. Hypogenitalism, hypogonadism, infertility

B. Intellectual disability, congenital malformations

C. Recurrent cases of chromosomal rearrangements

D. Multiple congenital malformations

E. Psychomotor retardation combined with hypopigmentation and unusual urine odor

21. Indications for biochemical genetic testing include all of the following EXCEPT:

A. Seizures, hyperexcitability, psychomotor retardation

B. Chronic pneumonia, intestinal malabsorption, hypotrophy

C. Cataracts, hepatosplenomegaly, developmental delay

D. Microcephaly, Hypertension, hypopigmentation, delayed motor and speech development

E. Congenital malformations

22. Which of the following methods are used to diagnose fragile X syndrome?

A. Syndromological Diagnostics, karyotyping

B. Syndromological diagnostics, biochemical methods, DNA diagnostics

C. Genealogical method, portrait diagnostics

D. Karyotyping, DNA diagnostics, syndromological diagnostics

E. Syndromological diagnostics, biochemical method, karyotyping

23. A medical genetics center is evaluating an 8-year-old child with growth retardation, kyphoscoliosis, short neck ("bull neck" appearance), scaphocephaly, joint stiffness, camptodactyly, cataracts, and Hearing loss. Intelligence is relatively preserved. Large amounts of glycosaminoglycans (keratan sulfates) are excreted in the urine. What is the most likely diagnosis?

A. Mucopolysaccharidosis

B. Sphingolipidosis

C. Glycogen storage disease

D. Marfan syndrome

E. Achondroplasia

24. A 1-month-old boy presents with vomiting, tachycardia, signs of dehydration, hyperpigmentation of the areolar region and genitalia, hyponatremia, hyperkalemia, and a 46,XY karyotype. What is your provisional diagnosis?

A. Pyloric stenosis

B. Galactosemia

C. Cystic fibrosis

D. Adrenogenital syndrome

E. Phenylketonuria

25. A 6-year-old girl with developmental delay, chest deformity, asymmetrical trunk, kyphoscoliosis, scaphocephaly, hepatosplenomegaly, and coarse Hair has a provisional diagnosis of mucopolysaccharidosis. Which tests will be most informative to confirm the diagnosis?

A. Funduscopy

B. Determination of glycosaminoglycan excretion

C. Determination of Aminoaciduria

D. Ferric chloride test

E. Karyotyping

Task 2

The table presents clinical scenarios. Indicate which of the listed genetic terms best defines each of them.