Internal medicine - Clinical genetics

Question 1

INT - 16.1
Among the following monogenic diseases predisposing for tumorigenesis which one is not autosomal dominantly inherited?
A) multiple endocrine neioplasia type 1

B) von Hippel–Lindau disease

C) ataxia teleangiectasia

D) multiple endocrine neioplasia type 2

E) neurofibromatosis type 1

Answer 1

ANSWER
C) ataxia teleangiectasia

EXPLANATION
The majority of monogenic tumor syndromes are autosomal dominantly inherited as multiple endocrine neoplasias type 1 and 2, von Hippel-Lindau disease and the most prevalent monogenic tumor syndrome, neurofibromatosis type 1. Ataxia teleangiectasia predisposes to lymphoma and cerebellar degeneration. The error of DNA repair enzymes leads to the formation of ataxia teleangiectasia, Bloom-syndrome, xeroderma pigmentosum, Fanconi-anaemia ataxia teleangiectasia all of which are autosomal recessively inherited.

Question 2

INT - 16.2
At which pregnancy age is amniocentesis recommended?
A) 4–6 weeks

B) 10–12 weeks

C) 15–17 weeks

D) 20–22 weeks

E) 24–26 weeks

Answer 2

ANSWER
C) 15–17 weeks

EXPLANATION
Amniocentesis is regularly performed at 15-17 weeks of pregnancy.

Question 3

INT - 16.3
Among the following chromosome abnormalities which one is the most frequent?
A) Turner-syndrome

B) Edwards-syndrome

C) Down-syndrome

D) Patau-syndrome

E) Williams-syndrome

Answer 3

ANSWER
C) Down-syndrome

EXPLANATION
Among the listed chromosome abnormalities Down syndrome is the most frequent with an incidence in live-borns of approximately 1:800. The other listed chromosome abnormalities are much rarer.

Question 4

INT - 16.4
What does the term penetrance mean?
A) the frequency of a genetic alteration

B) the frequency of a certain phenotype int he case of a certain genotype

C) a form of genetic regulation

D) the expression of small molecular weight RNAs

E) region of chromosomal regulation

Answer 4

ANSWER
B) the frequency of a certain phenotype int he case of a certain genotype

EXPLANATION
Penetrance means the ”power” of a certain genotype to produce a certain phenotype and show how frequent a certain phenotype is in case of a certain genotype. Some diseases are characterized by high penetrance (e.g. medullary thyroid cancer in the case of multiple endocrine neoplasia type 2 is present in approximately 100%) while other diseases have low penetrance (in the case of haemochromatosis only 1%).

Question 5

INT - 16.5
What proportion of the human genome is protein-coding?
A) 3%

B) 10%

C) 25%

D) 40%

E) 60%

Answer 5

ANSWER
A) 3%

EXPLANATION
The proportion of protein-coding regions in the human genome is only 3%. Previously, the rest 97% was considered ”junk DNA” not having any relevance in gene expression. However, recent data confirmed important regulatory regions within this 97% and utmost importance of the non-coding genome in species specificity and variability has been shown as well.

Question 6

INT - 16.6
Which one of the following diseases has the lowest penetrance?
A) multiple endocrine neoplasia type 1

B) multiple endocrine neoplasia type 2

C) neurofibromatosis type 1

D) cystic fibrosis

E) haemochromatosis

Answer 6

ANSWER
E) haemochromatosis

EXPLANATION
The penetrance of haemochromatosis is the lowest (under 1%), all of the others have higher penetrance (some components of multiple endocrine neoplasias, as medullary thyroid cancer in MEN2 or primary hyperparathyroidism in MEN1 are characterized with approximately 100% penetrance). Haemachromatosis may arise due to mutations in multiple genes (HFE, hepcidin, hemojuvelin), however in case of a mutation, only a fraction of patients presents symptoms. Therefore the genetic screening for haemochromatosis is not recommended.

Question 7

INT - 16.7
Which one of the following diseases does not predispose to pheochromocytoma?

A) von Hippel–Lindau disease

B) Gardner syndrome

C) multiple endocrine neoplasia type 2

D) neurofibromatosis type 1

E) inherited paraganglioma syndromes

Answer 7

ANSWER
B) Gardner syndrome

EXPLANATION
Interestingly, monogenic tumor syndromes are in the background of 25-30% of sporadically observed pheochromocytomas. Multiple endocrine neoplasia type 2, von Hippel-Lindau disease, neurofibromatosis type 1 and inherited paraganglioma syndromes all predispose to pheochromocytoma, with inherited paraganglioma syndromes specifically predispose to extraadrenal pheochromocytoma (paraganglioma). However, Gardner syndrome which predisposes to gastrointestinal polyposis does not predispose to pheochromocytoma.

Question 8

INT - 16.8
By definition, what is the frequeny of a mutation?
A) < 1%

B) < 5 %

C) < 10%

D) < 20%

E) < 30%

Answer 8

ANSWER
A) < 1%

EXPLANATION
By definition the frequency of a mutation in the population is under 1%

Question 9

INT - 16.9
What does the term compound heterozygosity mean?
A) More mutations are responsible for a certain disease in autosomal dominantly inherited syndrome.

B) The importance of Y chromosome alterations in sex-linked inheritance.

C) In the case of autosomal recessively inherited disease, different mutations on different allelles of the same gene are jointly responsible for the develeopment of the disease.

D) A rare regulatory mechanism in the case of X-linked dominant inheritance

E) The emergence of different pheotypes due to different mutations int he case of autosomal recessively inherited diseases.

Answer 9

ANSWER
C) In the case of autosomal recessively inherited disease, different mutations on different allelles of the same gene are jointly responsible for the develeopment of the disease.

EXPLANATION
In the case of compound heterozygosity two different mutaions are present on the two different alleles of the same gene. It occurs in cases of autosomal recessively inherited diseases. As with homozygote mutants, both alleles harbor disease-causing mutations, however the mutations differ. In the case of compound heterozygosity blood relations between the parents are not likely.

Question 10

INT - 16.10
Which pattern of inheritance is characteristic to blood relation between parents?
A) autosomal dominant

B) autosomal recessive

C) X-linked dominant

D) X-linked recessive

E) polygenic

Answer 10

ANSWER
B) autosomal recessive

EXPLANATION
In the case of blood relation between parents the chance of presence of two rare, recessively inherited alleles of the same gene is higher than in the general population. Therefore, blood relation between parents is more common in cases of autosomal recessively inherited diseases.

Question 11

INT - 16.11
What is the chance of the emergence of an autosomal recessively inherited disease in the offspring of two heterozygote carriers?
A) 10%

B) 25%

C) 40%

D) 50%

E) 60%

Answer 11

ANSWER
B) 25%

EXPLANATION
In the case of autosomal recessive inhertiance, the possibility of the inheritance of the mutant allele from two healthy heterozgote parents is 50-50%. The possibility of the inheritance of two mutant alleles is 0.5×0.5 = 0.25 = 25%. Therefore, statistically in one quarter of the offspring will the disease emerge.

Question 12

INT - 16.12
What is the chance of emergence of an autosomal dominantly inherited disease in one child of an affected heterozygote individual?
A) 10%

B) 25%

C) 40%

D) 50%

E) 60%

Answer 12

ANSWER
D) 50%

EXPLANATION
A heterozygote individual passes over the mutant allele with 50% chance to the offspring. Since in the case of autosomal dominantly inherited disease the presence of only one damaged allele is enough for the emergence of the disease, the inheritance of the disease is 50% as well.

Question 13

INT - 16.13
For which mode of inheritance is the following statement true: of the offspring of an affected male and a healthy female, all sons are healthy and all daughters are affected?
A) X-linked recessive

B) X-linked dominant

C) autosomal recessive

D) autosomal dominant

E) polygenic

Answer 13

ANSWER
B) X-linked dominant

EXPLANATION
The affected male passes his Y chromosome only to his sons, while passes his X chromosome only to his daughters. Therefore, in the case of X-linked dominant inheritance, all sons are healthy, while, due to the inheritance of the damaged X chromosome, all daughters are affected.

Question 14

INT - 16.14
Among the following diseases, in which case does genomic imprinting not constitute to the pathogenesis?
A) Prader–Willi syndrome

B) Angelman syndrome

C) Beckwith–Wiedemann syndrome

D) cystic fibrosis

Answer 14

ANSWER
D) cystic fibrosis

EXPLANATION
In the case of genomic imprinting, paternal and maternal alleles operate differently on certain gene loci. Genomic imprinting possesses role in the pathogenesis of Prader-Willi syndrome, Angelman syndrome and Beckwith-Wiedemann syndrome, however it does not constitute to the pathogenesis of cystic fibrosis.

Question 15

INT - 16.15
Over what frequency of occurrence in the general population is a genetic variant considered a polymorphism?
A) 1%

B) 7%

C) 10%

D) 15%

E) 20%

Answer 15

ANSWER
A) 1%

EXPLANATION
A genetic variant is considered a genetic polymorphism if its occurrence is over 1% in the general population

Question 16

INT - 16.16
The trisomy of which chromosome is the most frequent in live-born new-borns?
A) 13

B) 17

C) 19

D) 21

E) 22

Answer 16

ANSWER
D) 21

EXPLANATION
The most frequent trisomy in live-born new-borns is the trisomy of chromosome 21 (Down syndrome).

Question 17

INT - 16.17
Which chromosomal abnormality affecting the sex chromosomes has the highest incidence?
A) Turner syndrome

B) Klinefelter syndrome

C) Triple X sydrome (superfemale)

D) 46XX male

E) 46XY female

Answer 17

ANSWER
B) Klinefelter syndrome

EXPLANATION
The incidence of Klinefelter syndrome is 1:500 male live-borns. This is the most fequent chromosomal abnormality affecting the sex chromosomes.

Question 18

INT - 16.18
For which listed chromosome abnormality are the following symptoms characteristic: immunodeficiency, hypoparathyroidism, congenital heart defect?
A) Cri du chat syndrome

B) DiGeorge syndrome

C) Down syndrome

D) Turner syndrome

E) Prader–Willi syndrome

Answer 18

ANSWER
B) DiGeorge syndrome

EXPLANATION
Upon the damage of chromosome 22 (22q11 deletion) do the symptoms representative of DiGeorge syndrome (congenital heart defects e.g. tetralogy of Fallot and pulmonal atresia, hypoparathyroidism, and immunodeficiency due to thymic aplasia) emerge.

Question 19

INT - 16.19
Which one of the following symptoms is not characteristic to Turner syndrome?
A) short stature

B) streak gonad

C) primary amenorrhea

D) asthma bronchiale

E) coarctation of the aorta

Answer 19

ANSWER
D) asthma bronchiale

EXPLANATION
Short stature, primary amenorrhea due to streak gonad, congenital heart defect are characteristics of Turner syndrome, while asthma bronchiale is not.

Question 20

INT - 16.21
Amog the following diseases which one is not autosomal dominantly inherited?
A) Marfan syndrome

B) cystic fibrosis

C) Huntington’s disease

D) familial adenomatosus polyposis

E) hereditary retinoblastoma

Answer 20

ANSWER
B) cystic fibrosis

EXPLANATION
Cystic fibrosis is autosomal recessively inherited while Marfan syndrome, Huntington’s disease, familial adenomatosus polyposis and hereditary retinoblastoma are autosomal dominantly inherited.

Question 21

INT - 16.22
Which statement is false for phenylketonuria?
A) autosomal recessively inherited

B) it is the consequence of mutations of the gene encoding phenylalanine hydroxylase

C) the main symptoms are diarrhea and secondary malabsorption

D) elevated phenylalanine levels cause severe neurological symptoms

E) it is screened routinely in new-borns

Answer 21

ANSWER
C) the main symptoms are diarrhea and secondary malabsorption

EXPLANATION
Phenylketonuria is a autsomal recessively inherited disease which develops due to mutations of the gene encoding phenlyalanine hydroxylase. All new-borns are screened for this disease. Without treatment, severe neurological symptoms develops, while diarrhea and secondary malabsorption are not characteristics of the disease.

Question 22

INT - 16.23
Which one of the following hereditary metabolic diseases affect purine metabolism?
A) Tay–Sachs disease

B) Niemann–Pick disease

C) Hurler syndrome

D) Rett syndrome

E) Lesch–Nyhan syndrome

Answer 22

ANSWER
E) Lesch–Nyhan syndrome

EXPLANATION
Lesch-Nyhan syndrome affect the purine metabolism due to mutations of the gene encoding hypoxanthine-guanine phosphoribosyltransferase. Tay-Sachs disease is the consequence of mutations of the hexosaminidase A. Niemann–Pick disease is a kind of sphingolipidosis, while Hurler syndrome is a mucopolysaccharidosis. Rett syndrome is a severe neurological disease emerging as the consequence of MEPC2 mutations. MEPC2 possesses an important role in the creation of the metilation signature.

Question 23

INT - 16.24
Which one of the following statements is false for cystic fibrosis?
A) the most common fatal autosomal recessive disorder among Caucasian race

B) the frequency of carriers is 1/25

C) the frequency of carriers is 1/500

D) it is the consequence of mutations of a protein involved in the transport of chloride ions.

E) ΔF508 is the most common mutation.

Answer 23

ANSWER
C) the frequency of carriers is 1/500

EXPLANATION
Cystic fibrosis is the most common fatal autosomal recessive disorder among Caucasian race. The frequency of carriers is 1/25. The disorder is the consequence of of mutations of a protein involved in the transport of chloride ions (CFTR), among which ΔF508 is the most common.

Question 24

INT - 16.25
Which one of the following symptoms is not characteristic of cystic fibrosis?
A) chronic obstructive pulmonary disease

B) deficiency of the exocrine pancreas

C) diabetes mellitus

D) meconium ileus in new-borns.

E) male infertility due to absence of vas deferens

Answer 24

ANSWER
C) diabetes mellitus

EXPLANATION
Although one main symptom of cystic fibrosis is exocrine pancreas deficiency, endocrine pancreas is not affected, therefore diabetes mellitus is not a characteristic of the disease. Important manifestations include chronic obstructive pulmonary disease, meconium ileus in new-borns and the absence of vas deferens.

Question 25

INT - 16.26
Which one of the following is false regarding Duchenne muscular distrophy?
A) X-linked recessive inheritance

B) it is the consequence of mutations of the largest human protein, dystrophin

C) one manifestation is the pseudohypertrophy of the calves

D) weakness of the muscles begins in adulthood

E) elevated serum levels of creatine kinase

Answer 25

ANSWER
D) weakness of the muscles begins in adulthood

EXPLANATION
Duchenne muscular distrophy follows X-linked recessive inheritance and is the consequence of mutations of the gene encoding the largest human protein, dystrophin. Although the calves seem to be muscular, however instead of muscle it is mainly connective tissue (pseudohypertrophy). The disease start sin the childhood and due muscle damage, serum creatine kinase levels arises.

Question 26

INT - 16.27
Which of the following statements is false for Huntington’s disease?
A) it belongs to trinucleotide repeat disorders

B) it follows autosomal dominant inheritance

C) the disease manifestates in adulthood, usually after 40 years of age

D) one manifestation is severe hypertension

E) during familial inheritance, the first symptoms presents at earlier age in the offspring of the affected father (anticipation)

Answer 26

ANSWER
D) one manifestation is severe hypertension

EXPLANATION
Huntington’s disease is a trinucleotide repeat disroder inherited in autosomal dominant manner. The disease amnfiestates at adulthood, usually after 40 years of age. During familial inheritance, the first symptoms presents at earlier age in the offspring of the affected father (anticipation). However, hypertension is not a manifestation of Huntington’s disease.

Question 27

INT - 16.28
Which of the following disorder is not a trinucleotide repeat disorder?
A) fragile X syndrome

B) myotonic dystrophy

C) Huntington’s disease

D) Friedreich’s ataxia

E) Rett syndrome

Answer 27

ANSWER
E) Rett syndrome

EXPLANATION
Four main disorders constitue the trinucleotide repeat disorders: fragile X syndrome, myotonic dystrophy, Huntington’s disease and Friedreich’s ataxia. Rett syndrome, a severe neurological disease emerging as the consequence of MEPC2 mutations is not a trinucleotide repeat disorder.

Question 28

INT - 16.29
Which one of the following is not characteristic to diseases of the mitochondrial DNA?
A) they can be inherited from the mother and from the father

B) by a main rule, they can be inherited only from the mother

C) main characteristics include the disorders of the nervous system (including the sensory nervous system) and the muscle system

D) there may be wide phenotype variability

E) heteroplasmy is one of the main reasons of phenotype variability

Answer 28

ANSWER
A) they can be inherited from the mother and from the father

EXPLANATION
Generally, mitochondria originate from the oocyte, therefore disorders of the mitochondrial DNA can only be inherited maternally. Main characteristics include the disorders of the nervous system (including the sensory nervous system) and the muscle system and phenotype variability is very common. Heteroplasmy indicates the homogeneity of mitochondria within a cell. In the case of homoplasmy, all mitochondria carries identical genetic information, while in the case of heteroplasmy, mitochondria within the cell carries different genetic information.

Question 29

INT - 16.30
Which following characteristic is false for acute intermittent porphyria?
A) autosomal dominant inheritance

B) high penetrance

C) mutations of porphobilinogen deaminase are responsible for the disease

D) severe abdominal pain which cannot be explained by organic reasons

E) vegetative nervous system is often affected

Answer 29

ANSWER
B) high penetrance

EXPLANATION
Acute intermittent porphyria presents important differential diagnostic challange in the diagnosis of recurring severe abdominal pain which cannot be explained by organic reasons. It is inherited in autosomal dominant manner, however the penetrance is low, therefore many porphobilinogen deaminase mutation carrier does not present symptoms. In acute intermittent porphyria the vegetative nervous system is often affected.

Question 30

INT - 16.31
Which apolipoprotein E allele is linked to Alzheimer’s disease?
A) APOA

B) APOC

C) APOE1

D) APOE2

E) APOE4

Answer 30

ANSWER
E) APOE4

EXPLANATION
APOE4 allele is linked to Alzheimer’s disease.

Question 31

INT - 16.32
Which of the following vitamin’s deficiency has been mostly associated with the development of neural tube defects?
A) vitamin B1

B) vitamin B2

C) folic acid

D) vitamin C

E) vitamin A

Answer 31

ANSWER
C) folic acid

EXPLANATION
Neural tube defects has been associated with folic acid deficiency.

Question 32

INT - 16.33
Which hereditary tumor syndrome does not predispose to breast cancer?
A) Li-Fraumeni syndrome

B) mutations of BRCA1 gene

C) mutations of BRCA2 gene

D) von Hippel–Lindau disease

E) Cowden syndrome

Answer 32

ANSWER
D) von Hippel–Lindau disease

EXPLANATION
Li-Fraumeni syndrome, caused by mutations of p53 and Cowden syndrome, caused by mutations of PTEN predisposes to breast cancer. BRCA1 (breast cancer 1) and BRCA2 (breast cancer 2) mutations also predispose to breast cancer. Main characteristics of von Hippel-Lindau disease are renal cancer, pancreatic cysts and cancer, retinal and cerebellar hemangioblastomas, however breast cancer is usually not associated.

Question 33

INT - 16.34
Which of the following syndromes is not associated with chromosomal instability arising from deficient DNA repair?
A) neurofibromatosis type 1

B) ataxia teleangiectasia

C) Bloom syndrome

D) xeroderma pigmentosum

E) Fanconi anemia

Answer 33

ANSWER
A) neurofibromatosis type 1

EXPLANATION
Chromosomal instability as the consequence of deficient DNA repair constitute to the pathogenesis of the autosomal recessively inherited ataxia teleangiectasia, Bloom syndrome, xeroderma pigmentosum and Fanconi anemia. However it does not play a role in the pathogenesis of neurofibromatosis type 1, the most common tumor syndrome which is associated with the altered activity of Ras signaling.

Question 34

INT - 16.35
At which pregnancy age is chorionic villus sampling recommended to be performed?
A) 4–6 weeks

B) 10–12 weeks

C) 14–16 weeks

D) 18–20 weeks

E) 24–26 weeks

Answer 34

ANSWER
B) 10–12 weeks

EXPLANATION
Chorionic villus sampling is regularly performed at 10-12 weeks of pregnancy.

Question 35

INT - 16.36
When is prenatal diagnostical procedures recommended?
A) advanced maternal age

B) de novo chromosome abnormality in the previous child

C) one parent carries structural chromosomal alteration

D) in all three of the previous cases

E) none of the previous cases

Answer 35

ANSWER
D) in all three of the previous cases

EXPLANATION
Prenatal diagnostical procedures are recommended in all three of the cases: advanced maternal age, de novo chromosome abnormality in the previous child and if one parent carries structural chromosomal alteration

Question 36

INT - 16.37
Which of the following disorders cannot be detected by fetal utrasound imaging?
A) holoprosencephaly

B) neural tube defects

C) omphalocele

D) Huntington’s disease

E) cystic hygroma

Answer 36

ANSWER
D) Huntington’s disease

EXPLANATION
Symptoms of Huntington’s disease develop only in adulthood, therefore cannot be detected on fetal ultrasound imaging. However, prenatal molecular genetics diagnostics can detect disease causing alteration of the HTT gene.

Question 37

INT - 16.38
Which two chromosomes are affected by translocation in the case of Philadelphia chromosome?
A) 9 and 22

B) 8 and 14

C) 9 and 14

D) 8 and 22

E) 10 and 14

Answer 37

ANSWER
A) 9 and 22

EXPLANATION
Philadelphia chromosome which is usually observed in chronic myeloid leukemia results from the reciprocal translocation of chromosomes 9 and 22 creating a fusion gene called BCR-ABL.

Question 38

INT - 16.39
Which one of the following is not a characteristic of the fragile X syndrome?
A) it causes moderate mental retardation in affected boys and mild mental retardation in affected girls

B) it belongs to trinucleotide repeat disorders

C) enlarged testicles is a characteristic of the disease in affected boys

D) congenital heart defects are fequently observed

E) the disease is the consequence of FMR1 gene mutations

Answer 38

ANSWER
D) congenital heart defects are fequently observed

EXPLANATION
Fregile X syndrome causes moderate mental retardation in affected boys and mild mental retardation in affected girls. Being an important cause for mental retardation, fragile X syndrome is caused by mutations of FMR1 gene. The disease belongs to trinucleotide repeat disorders. Interestingly, enlarged testicles is a characteristic of the disease in affected boys. However, congenital heart defects are not associated to fragile X syndrome.

Question 39

INT - 16.40
Which one of the following is not a characteristic of glucose-6-phosphate dehydrogenase deficiency?
A) X-linked recessive inheritance

B) frequently observed in Mediterranean countries

C) predisposes to hemolytic anemia in homozygotes

D) mental retardation is frequent

E) heteroygosity may have a protective effect against malaria

Answer 39

ANSWER
D) mental retardation is frequent

EXPLANATION
Glucose-6-phosphate dehydrogenase deficiency is inherited in a X-linked recessive manner. It is frequent in Mediterranean countries and heterozygosity probably has a protective effect against malaria. In homozygotes, it predisposes to hemolytic anemia. However, mental retardation is not a characteristic of glucose-6-phosphate dehydrogenase deficiency

Question 40

INT - 16.41
Which of the following diseases is inherited in autosomal dominant manner?
A) multiple andocrine neoplasia type 1

B) neurofibromatosis type 1

C) von Hippel–Lindau disease

D) all three of them

E) neither of them

Answer 40

ANSWER
D) all three of them

EXPLANATION
All three mentioned hereditary tumor syndrome (multiple andocrine neoplasia type 1, neurofibromatosis type 1 and von Hippel–Lindau disease) are inherited in autosomal dominant manner.

Question 41

INT - 16.42
Which chromosome is affected in Prader-Willi syndrome?
A) 3

B) 12

C) 15

D) 17

E) 19

Answer 41

ANSWER
C) 15

EXPLANATION
Alterations of chromosome 15 (15q11-13) are responsible for Prader-Willi syndrome. Moreover, genomic imprinting is involved.

Question 42

INT - 16.43
Which of the following is false for Tay-Sachs disease?
A) lysosomal storage disease

B) Lisch nodules of the iris is a characteristic

C) cherry-red spot on the retina is a characteristic

D) neurodegenerative disease

E) hexosaminidase A deficiency plays a role int he pathogenesis

Answer 42

ANSWER
B) Lisch nodules of the iris is a characteristic

EXPLANATION
Tay-Sachs disease is a lysosomal storage disease, for which mutations in hexosaminidase A gene are responsible. It is a severe neurodegenerative disease. One of the characteristics is cherry-red spot on the retina. However, Lisch nodules of the iris is not present in Tay-Sachs disease, being a characteristic of neurofibromatosis type 1.

Question 43

INT - 16.44
Which of the following is the most severe manifestation of thalassaemia?
A) HbH disease

B) hydrops fetalis

C) hemolytic anemia

D) cerebral infarction

E) extramedullary hematopoiesis

Answer 43

ANSWER
B) hydrops fetalis

EXPLANATION
The most severe clinical manifestation of thalassaemia is hydrops fetalis.

Question 44

INT-16.46-16.50
Associate the following symptoms with the appropriate monogenic disease!
A) Marfan syndrome

B) cystic fibrosis

C) haemophilia (A and B)

D) Duchenne muscular dystrophy

E) Huntington’s disease

INT - 16.46 - hemorrhagic diatheses, hemarthrosis, decisively boys are affected

INT - 16.47 - manifestates in adulthood, severe neurodegenerative disease, autosomal dominantly inherited

INT - 16.48 - Severe muscle weakness, pseudohypertrophy of the calves, mild mental retardation, X-linked inheritance

INT - 16.49 - Chronic obstructive pulmonary disease, pancreatic deficiency, meconium ileus in new-borns, infertility secondary to the atresia of the vas deferens

INT - 16.50 - tall, dysmorphic stature, alterations of the skeletal structure, ectopic eyepiece, mitral valve prolapse, dilation and rupture of the aorta

Answer 44

ANSWER
INT - 16.46 - hemorrhagic diatheses, hemarthrosis, decisively boys are affected- C)

INT - 16.47 - manifestates in adulthood, severe neurodegenerative disease, autosomal dominantly inherited- E)

INT - 16.48 - Severe muscle weakness, pseudohypertrophy of the calves, mild mental retardation, X-linked inheritance- D)

INT - 16.49 - Chronic obstructive pulmonary disease, pancreatic deficiency, meconium ileus in new-borns, infertility secondary to the atresia of the vas deferens- B)

INT - 16.50 - tall, dysmorphic stature, alterations of the skeletal structure, ectopic eyepiece, mitral valve prolapse, dilation and rupture of the aorta -A)

Question 45

INT-16.51-16.55
Associate the following symptoms with the appropriate monogenic tumor syndrome!
A) multiple endocrine neoplasia 2A

B) neurofibromatosis type 1

C) von Hippel–Lindau disease

D) Li–Fraumeni syndrome

E) multiple endocrine neoplasia type 1

INT - 16.51 - clear cell renal cell carcinoma, pheochromocytoma, retinal and cerebellar hemangioblastoma, pancreatic cysts and neuroendocrine tumor

INT - 16.52 - parathyroid hyperplasia, endocrine pancreatic tumors, pituitary adenoma

INT - 16.53 - medullary thyroid cancer, pheochromocytoma, hyperparathyroidism

INT - 16.54 - neurofibroma, neurofibrosarcoma, brain tumor, pheochromocytoma

INT - 16.55 - breast cancer, brain tumor, adrenocortical cancer, sarcomas, leukemia

Answer 45

ANSWER
INT - 16.51 - clear cell renal cell carcinoma, pheochromocytoma, retinal and cerebellar hemangioblastoma, pancreatic cysts and neuroendocrine tumor- C)

INT - 16.52 - parathyroid hyperplasia, endocrine pancreatic tumors, pituitary adenoma- E)

INT - 16.53 - medullary thyroid cancer, pheochromocytoma, hyperparathyroidism- A)

INT - 16.54 - neurofibroma, neurofibrosarcoma, brain tumor, pheochromocytoma- B)

INT - 16.55 - breast cancer, brain tumor, adrenocortical cancer, sarcomas, leukemia- D)

Question 46

INT-16.56-16.60
Associate the following symptoms with the appropriate chromosomal diseases!
A) Prader–Willi syndrome

B) Turner syndrome

C) Down syndrome

D) Klinefelter syndrome

E) Edwards syndrome

INT - 16.56 - Mental retardation, severe developmental disorder, congenital heart defects, prominent occiput, abnormally small jaw, low-set, malformed ears, affected individuals rarely survive beyond childhood

INT - 16.57 - mental retardation, short stature, brachycephaly, flat nape, epicanthic fold, congenital heart defects

INT - 16.58 - Primary hypogonadism, infertility, tall stature, gynecomastia

INT - 16.59 - hypotonia and poor feeding during infancy, which turns to hyperphagia and extreme obisity during childhood, disproportionally smaller hands and toes, cognitive disturbancies, reproductive sterility

INT - 16.60 - Short stature, shield chest, webbed neck, streak gonad, cardiovascular malformations

Answer 46

ANSWER
INT - 16.56 - Mental retardation, severe developmental disorder, congenital heart defects, prominent occiput, abnormally small jaw, low-set, malformed ears, affected individuals rarely survive beyond childhood - E)

INT - 16.57 - mental retardation, short stature, brachycephaly, flat nape, epicanthic fold, congenital heart defects- C)

INT - 16.58 - Primary hypogonadism, infertility, tall stature, gynecomastia- D)

INT - 16.59 - hypotonia and poor feeding during infancy, which turns to hyperphagia and extreme obisity during childhood, disproportionally smaller hands and toes, cognitive disturbancies, reproductive sterility- A)

INT - 16.60 - Short stature, shield chest, webbed neck, streak gonad, cardiovascular malformations- B)

Question 47

INT-16.61-16.65
Associate the following patterns of inheritance with the characteristics!
A) autosomal recessive

B) autosomal dominant

C) X-linked recessive

D) X-linked dominant

E) polygenic, multifactorial inheritance

INT - 16.61 - From the relationship of affected males and healthy females all daughters are affected, while all sons are healthy. 50% of an affected female’s children may inherit the disease irrespective of the child’s sex.

INT - 16.62 - Familial history of the disease is a characteristic, however the pattern of inheritance does not follow monogenic Medelian inheritance. Emergence of the disease is more common in closer than further relatives of an affected individual.

INT - 16.63 - The disease is much more common in males. All daughters of an affected male will be carrier, while all sons will be healthy. Heterozygote females are usually healthy, however manifestations to some extent may be present.

INT - 16.64 - Typically, affected individuals are present in all generations. Every child of an affected individual has 50% chance to inherit the disease irrespective of sex. These diseases are less likely to alter life expectancy.

INT - 16.65 - These diseases are usually severe. Some generations do not have affected individuals. Blood relations are common in the family history of the affected families. Males and females are affected in the same frequency.

Answer 47

ANSWER
INT - 16.61 - From the relationship of affected males and healthy females all daughters are affected, while all sons are healthy. 50% of an affected female’s children may inherit the disease irrespective of the child’s sex.- D)

INT - 16.62 - Familial history of the disease is a characteristic, however the pattern of inheritance does not follow monogenic Medelian inheritance. Emergence of the disease is more common in closer than further relatives of an affected individual.- E)

INT - 16.63 - The disease is much more common in males. All daughters of an affected male will be carrier, while all sons will be healthy. Heterozygote females are usually healthy, however manifestations to some extent may be present.- C)

INT - 16.64 - Typically, affected individuals are present in all generations. Every child of an affected individual has 50% chance to inherit the disease irrespective of sex. These diseases are less likely to alter life expectancy.- B)

INT - 16.65 - These diseases are usually severe. Some generations do not have affected individuals. Blood relations are common in the family history of the affected families. Males and females are affected in the same frequency. - A)

Question 48

INT-16.66-16.72
Associate the following therapeutical approaches to the following genetic diseases!
A) dietary restrictions

B) enzyme replacement therapy

C) hormone replacement therapy

D)inhibitor administration

E) replacement of a specific protein (not enzyme)

INT - 16.66 - congenital hypothyroidism

INT - 16.67 - haemophilia A and B

INT - 16.68 - familial hypercholesterolemia

INT - 16.69 - Gaucher’s disease (glucocerebrosidase deficiency)

INT - 16.70 - α-1 antitrypsin deficiency

INT - 16.71 - phenylketonuria

INT - 16.72 - galactosemia

Answer 48

ANSWER
INT - 16.66 - congenital hypothyroidism- C)

INT - 16.67 - haemophilia A and B - E)

INT - 16.68 - familial hypercholesterolemia- D)

INT - 16.69 - Gaucher’s disease (glucocerebrosidase deficiency) - B)

INT - 16.70 - α-1 antitrypsin deficiency- E)

INT - 16.71 - phenylketonuria- A)

INT - 16.72 - galactosemia- A)

Question 49

INT-16.73-16.76
Associate the following sexual developmental disorders with the characteristics!
A) testicular feminization (Morris syndrome)

B) 21-hidroxylase deficiency (congenital adrenal hyperplasia)

C) Turner syndrome

D) Klinefelter syndrome

INT - 16.73 - Classical forms are associated with 45X0 kariotype.

INT - 16.74 - Disease is due to mutations of the androgen receptor.

INT - 16.75 - Serum levels of 17α-hydroxyprogesterone are elevated.

INT - 16.76 - The most frequent disorder affecting sex chromosomes.

Answer 49

ANSWER
INT - 16.73 - Classical forms are associated with 45X0 kariotype.- C)

INT - 16.74 - Disease is due to mutations of the androgen receptor.- A)

INT - 16.75 - Serum levels of 17α-hydroxyprogesterone are elevated.- B)

INT - 16.76 - The most frequent disorder affecting sex chromosomes.- D)

Question 50

INT-16.77-16.80
Associate the chance of the birth of affected child with the folowing cases (assume maximal penetrance)!
A) 25%

B) 50%

C) 100%

D) 0%

INT - 16.77 - In the daughters of an affected male and a healthy female in X-linked dominant inheritance

INT - 16.78 - In the relationship of two heterozygote in autosomal recessive inheritance

INT - 16.79 - In the relationship of an affected heterozygote and a healthy individual in autosomal dominant inheritance

INT - 16.80 - In the sons of an affected male and a healthy female in X-linked recessive inheritance

Answer 50

ANSWER
INT - 16.77 - In the daughters of an affected male and a healthy female in X-linked dominant inheritance- C)

INT - 16.78 - In the relationship of two heterozygote in autosomal recessive inheritance- A)

INT - 16.79 - In the relationship of an affected heterozygote and a healthy individual in autosomal dominant inheritance- B)

INT - 16.80 - In the sons of an affected male and a healthy female in X-linked recessive inheritance.- D)