Medical Genetics - V. M. Zaporozhan 2005

Chromosomal Diseases
Review questions for Chapter 5

1. What is The Significance of chromosomal and genomic Mutations in ontogeny?

2. What are Chromosomal Disorders? Population frequency.

3. Classification of chromosomal disorders: complete and mosaic forms, inherited and sporadic forms.

4. Characterize the Pathogenesis of chromosomal disorders.

5. Name the general symptoms of chromosomal disorders caused by Changes in the number and Structure of autosomes.

6. Polyploidy: karyotype, Clinical presentation, prognosis, MEDICAL Genetic Counseling for the family.

7. Down syndrome: karyotype, population frequency, correlation with maternal age. Clinical CHARACTERISTICS OF THE syndrome across different age periods, genetic risk calculation.

8. What is the clinical and cytogenetic profile of chromosomal disorders associated with changes in the number and structure of autosomes: Patau, Edwards, and cri-du-chat syndromes?

9. What are the distinctive Features of the Clinical presentation of chromosomal syndromes caused by alterations in the number of sex Chromosomes?

10. Clinical and cytogenetic characterization of Turner syndrome, X polysomy, Y polysomy, and Klinefelter syndrome.

11. What are microcytogenetic syndromes? Clinical Features and Examples of syndromes.

12. Angelman and Prader–Willi syndromes. The significance of Genomic Imprinting.

13. Diagnosis of chromosomal disorders. Cytogenetic Methods.

14. Principles of medical genetic counseling.

Control and study questions

Task 1

Choose one single answer.

1. A Robertsonian translocation can be the cause of:

A. Down syndrome

B. Turner syndrome

C. Cri-du-chat syndrome

D. Marfan Syndrome

E. Prader–Willi syndrome

2. Microcytogenetic syndromes include:

A. Down syndrome

B. Patau syndrome

C. Turner syndrome

D. Klinefelter syndrome

E. Prader — Willi syndrome

3. A 4-year-old boy with intellectual disability is diagnosed with Down syndrome. Indicate the correct karyotype formula for Down syndrome:

A. 46,XY, del 5p-

B. 47,XX,+13

C. 47,XX, + 18

D. 47,XY,+21

E. 45,X

4. A cytogenetics laboratory is analyzing the karyotype of a girl with symptoms of Turner syndrome. Which karyotype will confirm the diagnosis?

A. 47,XXY

B. 47,XY,+13

C. 47,XX, + 18

D. 46,XY, del 5p-

E. 45,X

5. A boy with intellectual disability and underdevelopment of secondary sex characteristics is diagnosed with Klinefelter syndrome. Indicate the correct karyotype formula for this syndrome:

A. 45,X

B. 47,XXX

C. 47,XYY

D. 47,XXY

E. 47,XY,+18

6. Which karyotype is characterized by a combination of microcephaly, moon face, antimongoloid slant of the eyes, epicanthus, and a specific cry?

A. 46,XXY

B. 47,XY,+18

C. 47,XY, + 13

D. 46,XX, del 5p-

E. 46,XY, del 4p-

7. A 15-year-old boy presents with tall stature, eugunoid body proportions, gynecomastia, and reduced testicular size. A buccal smear reveals a single Barr body (sex Chromatin clump). What is your diagnosis?

A. Down syndrome

B. Patau syndrome

C. Marfan syndrome

D. Klinefelter syndrome

E. Y-polysomy syndrome

8. A newborn girl exhibits microcephaly with scalp Skin defects (congenital aplasia cutis), cleft lip and palate, CNS malformations, and polydactyly. This symptom complex is characteristic of:

A. Down syndrome

B. Cri-du-chat syndrome

C. Patau syndrome

D. Edwards syndrome

E. Turner syndrome

9. A newborn girl presents with lymphedema of the hands and feet, a short webbed neck, antimongoloid slant of the eyes, and epicanthus. What is your diagnosis?

A. Down syndrome

B. Patau syndrome

C. Edwards syndrome

D. Cri-du-chat syndrome

E. Turner syndrome

10. A 14-year-old girl is referred to a medical genetics center. She is 139 cm tall, weighs 40 kg, and presents with an antimongoloid slant of the eyes, epicanthus, webbed neck, shield chest, widely spaced nipples (hypertelorism), cubitus valgus, multiple nevi, absence of secondary sexual characteristics, infantile habitus, and a left Kidney malformation; she is an A-grade student. What is your preliminary diagnosis?

A. X-polysomy syndrome

B. Angelman syndrome

C. Prader-Willi syndrome

D. Cri-du-chat syndrome

E. Turner syndrome

11. In the 1970s, population studies were conducted in Western Europe, the USA, and Canada to determine the frequency of chromosomal disorders caused by changes in the number and Structure of Sex chromosomes. It was established that one of these syndromes can present with normal physical and mental development; thus, the syndrome was discovered as an incidental cytogenetic finding in practically healthy individuals. Which syndrome is being referred to?

A. Klinefelter syndrome

B. Trisomy X ("superfemale")

C. Polysomy Y ("supermale")

D. Turner syndrome

12. Inheritance of a microdeletion on the long arm of chromosome 15 from the mother leads to Angelman syndrome, whereas inheritance from the father results in a different syndrome (Prader-Willi). This is explained by:

A. Incomplete Gene penetrance

B. Variable expressivity

C. Genomic imprinting

D. Complementary gene action

E. Pleiotropy

13. Which of the following is most characteristic of chromosomal disorders?

A. Delayed psychomotor development in early childhood, intellectual disability in older age

B. Impaired physical development, changes in urine color and odor

C. Systemic involvement

D. Impaired intellectual development, multiple congenital anomalies, and microanomalies

E. Cataracts, hepatosplenomegaly, developmental delay

14. A newborn boy presents with hypoplasia, dolichocephalic Skull shape, microgenia, low-set and malformed auricles, rocker-bottom feet, Heart defects, and Central Nervous system abnormalities. What is your diagnosis?

A. Down syndrome

B. Patau syndrome

C. Marfan syndrome

D. Klinefelter syndrome

E. Edwards syndrome

15. A newborn infant presents with brachycephaly, microcephaly, upward-slanting palpebral fissures, epicanthic folds, macroglossia, and a flat facies. Which chromosomal syndrome is this symptom complex most characteristic of?

A. Edwards syndrome

B. Patau syndrome

C. Down syndrome

D. Turner syndrome

E. Cri-du-chat syndrome

16. Chromosomal disorders in newborns can result from any alterations in chromosome number and structure, except for:

A. Nullisomy

B. Trisomy

C. Inversion

D. Monosomy

E. Duplication

17. Indicate the incidence of chromosomal disorders in newborns:

A. 1 in 700

B. 5 per 1,000

C. 0.1 %

D. 1 %

E. 5 %

18. At what maternal age does the probability of giving birth to children with chromosomal disorders increase sharply:

A. 20–25 years

B. 25–30 years

C. 30–35 years

D. 35 years and older

E. Independent of age

19. A 9-year-old boy presents with obesity, muscular hypotonia, acromicria (small hands and feet), hypogonadism, intellectual disability, and a microdeletion of the long arm of chromosome 15. What is your diagnosis?

A. Cri-du-chat syndrome

B. Angelman syndrome

C. Prader-Willi syndrome

D. Patau syndrome

E. Marfan syndrome

20. The combination of prenatal hypoplasia, microcephaly, microphthalmia, cleft lip and palate, and polydactyly is characteristic of:

A. Down syndrome

B. Cri-du-chat syndrome

C. Patau syndrome

D. Turner syndrome

E. Edwards syndrome

21. Indicate the Indications for Cytogenetic Diagnostics:

A. Mental retardation, minor developmental anomalies, and Congenital Malformations

B. Hepatosplenomegaly, cataract, mental retardation

C. Food intolerance, hemolytic crises

D. Neurological manifestations (seizures, decreased or increased Muscle tone, spastic paresis)

E. Unusual urine odor

22. Clinical manifestation during Puberty is characteristic of:

A. Down syndrome

B. Klinefelter syndrome

C. Turner syndrome

D. Cri-du-chat syndrome

E. Prader-Willi syndrome

Task 2

Analyze the following clinical scenarios.

1. A 26-year-old woman gave birth to a baby boy weighing 2,600 g, presenting with microcephaly, moon face, hypertelorism, epicanthus, high-arched palate, and low-set auricles. The child's cry resembles a kitten's meow.

What is your provisional diagnosis? Which laboratory methods will confirm the diagnosis?

2. A 4-month-old girl presents with a round HEAD and flattened occiput, mongoloid slant of the eyes, broad nasal bridge, epicanthus, low-set small auricles, and macroglossia. Her hands are broad and short with a single palmar crease and clinodactyly of the fifth fingers. There is marked muscular hypotonia and a "frog-leg" posture.

What is your provisional diagnosis? What is your examination plan?

3. A 30-year-old man presents with feminine-type fat distribution on the thighs, gynecomastia, and facial hairlessness. His Penis is of normal

size; his Testes are reduced in size, soft, and non-tender. Oligospermia is present.

What is your provisional diagnosis? What is your examination plan?

4. The proband is a 28-year-old woman who came to a medical genetics clinic regarding her two-month-old daughter's condition. The child is from her fourth Pregnancy. The First and Second pregnancies ended in spontaneous first-trimester abortions; the third resulted in a baby girl who died at the age of two days from multiple congenital malformations. The proband's husband is healthy, aged 32. The proband's sister and brother are healthy, and her parents are healthy; however, the maternal aunt had a child with mental retardation who died at the age of 15. The husband's brother, mother, and father are healthy. The husband's brother is married and has a healthy son and daughter. Phenotypically, the proband's daughter has been diagnosed with Down syndrome.

Draw the pedigree. Which genetic method will confirm the diagnosis in the proband's daughter? Which cytogenetic variant of Down syndrome might be suspected in this family? Which family members require genetic counseling?