GENETICS IN MEDICINE

Question 1

GENETIC COUNSELLING

Answer 1

process of communication with family focused on the problems of occurrence or recurrence risk of genetic diseases in family

Question 2

INDICATIONS FOR GENETIC COUNSELLING

Answer 2

-known or suspected genetic disease
-consanguinity
-male age over 50
-female age over 35
-chronic disease in woman
-familial occurrence or early onset of cancer
-repeated spontaneous abortions
-infertility
-atypical results of prenatal screening
-inborn defects or mental retardation
-exposure to teratogen during pregnancy

Question 3

MONOGENIC ORIGIN

Answer 3

mendelian heredity

Question 4

POLYGENIC ORIGIN

Answer 4

multifactorial

Question 5

CANCER DISEASE ORIGINS

Answer 5

somatic mutations

Question 6

METHODS OF DIGANOSIS AND PROGNOSIS

Answer 6

pedigrees
epidemiology stats
dysmorphology examination

Question 7

EXAMINATION TYPES

Answer 7

CYTOGENETICAL = karyotype, chromosomal aberrations, chromosomes of peripheral blood lymphocytes, AMC, CVS, fetal blood

BIOCHEMICAL = assessment of metabolites, concentration of metabolites, hormones, screening, enzyme activities

MOLECULAR GENETICS = detection of mutations

Question 8

INBORN DEFECTS

Answer 8

MALFORMATION = morphological defects resulting from abnormal development (monogenic, chromosomal and multifactorial))

DISRUPTION = breakdown or interferences with originally normal developmental process
(trauma, teratogen, thalidomide = sporadic or environmental)

DEFORMATION = abnormal form / shape / position caused by mechanical forces
(compression of fetus in oligohydramnion = low amnionic fluid during pregnancy)

DYSPLASIA = abnormal organization of cells into tissues (achronoplasia)

Question 9

MUTIPLE ANOMALIES EXAMPLE

Answer 9

SEQUENCE = multiple anomalies derived from a single anomaly

-POTTER SEQUENCE
renal agenesis -> oligohydramnion -> fetal compression -> flattened face -> abnormality of extremities -> pulmonary hyperplasia

Question 10

WHAT DOES TETERACYCLINE CAUSE?

Answer 10

disturbance in development of bones and teeth after 20th weel

Question 11

FETAL VALPROATE SYNDROME

Answer 11

craniofacial anomalies
cleft face defects
disturbance in neural tube development
inborn heart defects

CAUSED BY ANTICONVULSIVES

Question 12

FETAL HYDANTOINE SYNDROME

Answer 12

mental retardation
limb defects
cleft face defects
hypoplasia of middle face

CAUSED BY ANTICONVULSIVES

Question 13

INVASIVE PRENATAL SCREENING

Answer 13

AMC (AMNIOCENTESIS) = amniotic fluid cells examination after 16-18 weeks
-14 day cultivation
-cells grow in colonies on bottom of special bottle
-cytogenetical evaluation
-possibility of detection of trisomies and gonosomal abnormalities in 3 days

CVS (CHORIONIC VILLI CELLS) = chorionic villi cells examination between 10-12 weeks
-early method
-biopsy of tissue (fetal membranes)
-direct (surface cells) or indirect (integral) (cultivation) method

CORDOCENTESIS (FETAL BLOOD) = from umbilical cord after 20th week
-2 day cultivation

Question 14

INDICATOR FOR PRENATAL INVASIVE EXAMINATION

Answer 14

-advanced maternal age
-molecular diagnosis of disease
-abnormality on ultrasound or biochemical screen
-parent a carrier of balanced chromosomal aberration
-psychologic reasons

Question 15

NEONATAL SCREENING

Answer 15

sample of dry blood drop from newborns heel
-examination of mainly metabolic diseases

Question 16

PRESYMPTOMATIC SCREENING

Answer 16

detection of disease before its onset
-breast cancer / colon cancer in individuals with predisposition

Question 17

SYNDROME

Answer 17

multiples anomalies independent to each other, have a common cause (e.g. phenylketonuria)

Question 18

PHYSICAL TERATOGENS

Answer 18

DIAGNOSTIC IRRADIATION – X-ray till 10th day of more than 100mSv has lethal effect, after 10th causes inborn defects
o for examination outside uterus
§ <20mSv - without effect
§ >20mSv – consultation with radiologist
§ >100mSv – reason for ending gravidity, risk of inborn defects increases above 50%
o Examination with radioisotopes I
121 – spontaneous abortion, growth retardation, developmental disorders of the
CNS and eyes
o Ultrasound and MRI is okay, CT is not recommended

• HYPOTHERMIA - in first 6 weeks of gravidity
  o Hot bath, sauna - 3x higher risk of inborn defects
  o fever > 38.5oC lasting more than one day
  o spontaneous abortion, growth retardation, developmental disorder of the CNS, facial dysmorphia, hypotonia, hypertonia, neural tube defect (NTD)

-MECHANICAL CAUSES- uterus myomatosus – deformed uterus due to muscle tumours
o Amnial bands – premature breaking of the amniotic body, causes limb constriction – amputation)

Question 19

CHEMICAL TERATOGENS

Answer 19

FOOD / MEDS / DRUGS
- proved teratogens in 1rst trimester
o VITAMIN A – in high doses teratogenic, developmental defects of CNS, skull, earing apparatus, heart, limbs
o WARFARIN - anticoagulant, deformation of bones, cartilage and CMS
o CYTOSTATICS – stop cell proliferation, cardiopathy, osteopathy, spina bifida and other
o FAT SOLUBLE VITAMINES – stored in the body -> too much of anything is bad
o THALIDOMIDE – causes reduction defects in the limbs (mixture of thalidomide R a S)
- drugs
o SMOKES / COCAINE / LSD – risk of spontaneous abortion and growth retardation s
o CAFFEINE – more than 4 cups a day 4 – low birth weight, premature birth
o ALCOHOL – fetal alcohol syndrome, mental retardation, inborn heart defects, low birth weight, typical facial
dysmorphia (thin upper lip, no or slight groove between the lip and upper lip), wide nose root, short nose, short eyelids, small head circumference

Question 20

WHAT IS THE MAIN MATERNAL FACTOR TERATOGEN?

Answer 20

folic acid in high doses

Question 21

SECONDARY PREVENTION

Answer 21

-ultrasound
-biochemical screening
-methods of detection of inborn errors during pregnancy
-prenatal cytogenetic examination

Question 22

PRIMARY PREVENTION

Answer 22

-preconceptional care = starts before conception with the aim to prevent multifactorial/polygenic inborn errors
-prevention of the origin of an inborn error