GENETICS IN MEDICINE Flashcards
GENETIC COUNSELLING
process of communication with family focused on the problems of occurrence or recurrence risk of genetic diseases in family
INDICATIONS FOR GENETIC COUNSELLING
-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
MONOGENIC ORIGIN
mendelian heredity
POLYGENIC ORIGIN
multifactorial
CANCER DISEASE ORIGINS
somatic mutations
METHODS OF DIGANOSIS AND PROGNOSIS
pedigrees
epidemiology stats
dysmorphology examination
EXAMINATION TYPES
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
INBORN DEFECTS
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)
MUTIPLE ANOMALIES EXAMPLE
SEQUENCE = multiple anomalies derived from a single anomaly
-POTTER SEQUENCE
renal agenesis -> oligohydramnion -> fetal compression -> flattened face -> abnormality of extremities -> pulmonary hyperplasia
WHAT DOES TETERACYCLINE CAUSE?
disturbance in development of bones and teeth after 20th weel
FETAL VALPROATE SYNDROME
craniofacial anomalies
cleft face defects
disturbance in neural tube development
inborn heart defects
CAUSED BY ANTICONVULSIVES
FETAL HYDANTOINE SYNDROME
mental retardation
limb defects
cleft face defects
hypoplasia of middle face
CAUSED BY ANTICONVULSIVES
INVASIVE PRENATAL SCREENING
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
INDICATOR FOR PRENATAL INVASIVE EXAMINATION
-advanced maternal age
-molecular diagnosis of disease
-abnormality on ultrasound or biochemical screen
-parent a carrier of balanced chromosomal aberration
-psychologic reasons
NEONATAL SCREENING
sample of dry blood drop from newborns heel
-examination of mainly metabolic diseases
PRESYMPTOMATIC SCREENING
detection of disease before its onset
-breast cancer / colon cancer in individuals with predisposition
SYNDROME
multiples anomalies independent to each other, have a common cause (e.g. phenylketonuria)
PHYSICAL TERATOGENS
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)
CHEMICAL TERATOGENS
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
WHAT IS THE MAIN MATERNAL FACTOR TERATOGEN?
folic acid in high doses
SECONDARY PREVENTION
-ultrasound
-biochemical screening
-methods of detection of inborn errors during pregnancy
-prenatal cytogenetic examination
PRIMARY PREVENTION
-preconceptional care = starts before conception with the aim to prevent multifactorial/polygenic inborn errors
-prevention of the origin of an inborn error
