Modes of Inheritance
The Inheritance
 The inheritance trace the transmission of
genetically encoded traits, conditions or
diseases to offspring.
 There are several modes of inheritance:
 Single Gene or Mendelian
 Multifactorial
 Mitochondrial
Single Gene Inheritance
 Genetic condition is caused by a mutation in
a single gene follow predictable patterns of
inheritance within families.
 Single gene inheritance is also referred to as
Mendelian inheritance as that follow
transmission patterns J.G. Mendel observed
in his research on peas.
Laws of Mendel
 The law of unit of inhertitance – Inherited traits are
determined by genes. The allele is one form of the gene
 The law of dominance – the alleles occur in each individual in
the pair, but the effect of one allele can be overlapped by a
dominant effect of second allele
 The law of segregation – the alleles divide during
gametogenesis. Pairs of the allele resume during fertilization
 The law of free combination – the alleles of different genes
combine each other independently
Monogenic disorders
 Precise and well-established risks
can be given regarding its
occurrence in other family
members
 DNA analysis help in diagnostic
process
Monogenic diseases
 Typicaly in childhood- not exclusively!
 Less then10% manifest after puberty,
1% after reproductive age
 Incidence of monogenic disorders- 0,36%
Mendelian inheritance-types
There are four types of Mendelian
inheritance patterns:
Autosomal dominant
Autosomal recessive
X-linked recessive
X-linked dominant
Autosomal Dominant
 the gene responsible for the phenotype is
located on one of autosomes
 The sexes are involved equally
 Condition manifests in heterozygotes
 Affected individuals have one normal copy
of the gene and one mutant copy of the
gene
 each offspring has a 50% chance on
inheriting the mutant allele.
Pedigree AD inheritance
• the risk 50%
healthy
ill
AD - diseases
 Neurofibromatosis types I and II
 Achondroplasia
 Myotonic dystrophy
 Huntington disease
Neurofibromatoses
 member of the neurocutaneous syndromes (phakomatoses)
 NF type I
Café au lait spots,Neurofibromas, plexiform Neurofibromas
axillary and inguinary freckling, Iris Hamartomas(Lisch
nodules),MR 10-30%, skeletal symptoms
NF1 gene-neurofibromin(17q11.2)
 NF type II- central type-bilat.acoustic Neurinomas (Tumors of the
vestibulocochlear Nerve )-hearing loss, Meningiomas,
Ependymomas,Gliomas,Astrocytomas, juvenile cortical cataract
Retinal hamartoma ,no Lisch nodules
NF2 gene- merlin (22q12.2)
 Neoplasias
 Variation in expression
 50% new mutations.
Myotonic dystrophy I
 trinucleotide repeat expansion (CTG)n in the dystrophia
myotonica-protein kinase gene (DMPK) 19q13.32
 Myotonia (delayed muscle relaxation after contraction),
cataract,atrial arrythmias, hypogonadism, testicular atrophy
 congenital form(over 2000 repeats)-hypotonia, poor
feeding,severe mental retardation, prenatal polyhydramnios,
reduced fetal movement
 Myotonic dystrophy type 2 (DM2), also called proximal
myotonic myopathy (PROMM)-rarer than DM1 and
generally manifests with milder signs and symptoms.
 Specific defect -repeat of the CCTG tetranucleotide in the
ZNF9 gene (3q21.3).
Achondroplasia
Autosomal dominant with complete
penetrance
90% cases new mutations
100% of the mutations are G380R in FGFR3
Paternal age effect
Short-limb dwarfism identifiable at birth
Mean male adult height, 131 cm
mean female height, 124 cm
Frontal bossing ,megalencephaly
midface hypoplasia,low nasal bridge
Huntington disease
 a progressive disorder of motor, cognitive, and psychiatric
disturbances. The mean age of onset is 35 to 50 years and
the median survival time is 15 to 18 years after onset.
 The diagnosis of HD rests on positive family history,
characteristic clinical findings-Hyperreflexia ,Chorea ,Dementia
Bradykinesia ,Rigidity, psychiatric:depression,psychotic
symptoms, outbursts of aggression;
 expansion of 36 or more CAG trinucleotide repeats in HTT
(the huntingtin gene 4p16.3).
 Treatment of manifestations: neuroleptics ,anti-parkinsonian
agents , psychotropic drugs or some antiepileptic drugs .
Supportive care with attention to nursing needs, dietary
intake, special equipment, and eligibility for state benefits.
HD- genetic counseling
 Predictive testing in asymptomatic adults at 50% risk is
possible but requires careful thought
 including pretest and post-test genetic counseling
 Asymptomatic at-risk individuals younger than age 18 years
should not have predictive testing.
 prenatal testing by molecular genetic testing is possible for
pregnancies at 50% risk. Prenatal testing for pregnancies at
25% risk cannot be performed because genetic status of the
at-risk parent can reveal. Linkage analysis can be used for
preimplantation genetic diagnosis
 Families may benefit from referral to a local HD support group
for educational materials and psychological support.
Autosomal Recesive
 Recessive conditions are clinically manifest
only when an individual has two copies of
the mutant allele.
 Females and males are affected equally
 When two carriers mate, each child has a
25% chance of being homozygous wild-type
(unaffected); a 25% chance of being
homozygous mutant (affected); or a 50%
chance of being heterozygous (unaffected
carrier).
Pedegree - AR inheritance
•The risk for
next child 25%
carriercarrier
healthy illcarrier
healthy
Consanguinity
 Consanguineous marriage is the union of individuals
having a common ancestor. It is categorized as 1st,
2nd and 3rd degree
 Consanguineous marriages increase the risk of
manifestation autosomal recesive diseases in
offsprings
 genetic consanguinity is expressed
with the coefficient of relationship- is defined as the
fraction of homozygous due to the consanguinity
under discussion
AR - diseases
 Cystic fibrosis
(frequency of heterozygotes CR- 1/26)
 Phenylketounria (1/40)
 Congenital adrenal hyperplasia (1/40)
 Spinal muscular atrophy (1/60-80)
Cystic fibrosis
 Localized on chromosome 7q
 CFTR gene
 Frequency of Cystic Fibrosis in the Czech
Republic: about 1/3000
 Frequency of heterozygots in the Czech
Republic about 1/25-1/29
 About 1900 mutations in CFTR gene were
identified
CF-ethnical differences
frequence of CF frequence of heterozygotes
Caucasians 1/3000 1/25
Hispanics 1/9000 1/46
Amer. Africans 1/15000 1/60
Asians 1/32000 1/90
Cystic fibrosis
 Chronic bronchopulmonary infection
Bronchiectasis ,Asthma ,Pseudomonas
colonization
 Pancreatic insufficiency in 80%, Biliary
cirrhosis, Meconium ileus in neonates
(10-15%) Distal intestinal obstruction
syndrome Rectal prolapse
 Male infertility (98%) due to congenital
bilateral absence of the vas deferens
(CBAVD) ,Female decreased fertility due
to thickened cervical secretions and
chronic lung disease
 Laboratory Abnormalities - High sweat
sodium and chloride
Hyponatremic dehydratation, rarely
Hypercalciuria
Abnormal nasal potential differences
High newborn serum levels of
immunoreactive trypsinogen
The reason for CFTR gene
analysis
 Suspition on Cystic
fibrosis in a patient
 Cystic fibrosis in the
family
 Partners of
heterozygots for Cystic
fibrosis
 Repeated fetal loss
 Sterility
 Relationship of the
partners
 Others
Most frequent CFTR mutations in
Czech population
Mutation Frequency in CR (%)
F508del 70,7
CFTRdele2,3(21kb) 6,4
G551D 3,7
N1303K 2,8
G542X 2,1
1898+1 GtoA 2,0
2143delT 1,1
R347P 0,74
W1282X 0,6
Congenital adrenal
hyperplasia- CAH
 Group of congenital enzymatic defects of adrenal
steroidogenesis
 most frequent- 21-hydroxylase deficiency(CYP21
deficiency, 6p21)
CAH-symptoms
 Due to inadequate mineralocorticoids:
vomiting due to salt-wasting leading to
dehydratation and death
 Due to excess androgens:
virilization ,ambiguous genitalia, in some females,
such that it can be initially difficult to determine
sex, early pubic hair and rapid growth in childhood,
precociosus puberty or failure of puberty,infertility
due to anovulation,enlarged clitoris and shallow
vagina
Phenylketonuria-PKU
 Phenylalanine hydroxylase (PAH) deficiency results in
intolerance to the dietary intake of the essential amino acid
phenylalanine and produces a spectrum of disorders including
phenylketonuria (PKU), non-PKU hyperphenylalaninemia (nonPKU
HPA), and variant PKU.
 PAH gene 12q24
 Symptomes:intellectual disability and other serious health
problems -seizures, delayed development, behavioral
problems, psychiatric disorders are also common, lighter skin
and hair,eczemas
 Treatment elimination diet
 Diagnosis/testing. PAH deficiency can be diagnosed by
newborn screening
Spinal muscular atrophy-SMA
 Spinal muscular atrophy (SMA) is characterized by progressive
muscle weakness resulting from degeneration and loss of the
anterior horn cells ( lower motor neurons) in the spinal cord
and the brain stem nuclei. Onset ranges from before birth to
adolescence or young adulthood. Poor weight gain, sleep
difficulties, pneumonia, scoliosis, and joint contractures are
common complications.
 SMN1 gene(5q12.2-q13.3)- About 95%-98% of individuals
with SMA are homozygous for a deletion
 Clinical subtypes:
severe infantile acute SMA (Werdnig-Hoffman disease)
infantile chronic SMA
juvenile SMA,(Kugelberg-Welander disease)
adult-onset SMA.
X-linked Recesive
 traits are fully evident in males because they only
have one copy of the X chromosome.
 Females are not affected as severaly as males or are
not affected
 An affected male cannot transmit the trait to his sons,
because the trait is on X-chromosome, and the father
must necessarily transmit his Y-chromosome to a son
 All daughters of an affected male must be carriers,
because the only X-chromosome that the father can
give to a daughter contains the mutation
X-linked Recesive
 Risk for daughters of a carrier
mother- 50% for carrier
 Risk for sons of carrier mother
- 50% for disease
Pedigree
X- recesive inheritance
X
XY
XX
X
XY
XR - diseases
 Hemophilia A and B
 Duchenne and Becker muscular
dystrophy
Hemophilia
 Hemophilia A (clotting factor VIII
deficiency,F8,Xq28)- 80% cases
 Hemophilia B(factor IX deficiency, F9, Xq27)-20%
cases
 Characteristic symptoms vary with severity. In
general symptoms are internal or external bleeding
episodes
 Complication:deep muscle bleeding,haemarthrosis,intracranial
hemorrhage,adverse reaction to clotting factor
treatment,transfusion transmitted infection
Dystrophinopathies
 The dystrophinopathies include a spectrum of muscle disease caused
by mutations in DMD gene, which encodes the protein dystrophin-
Xp21.2
 Duchenne muscular dystrophy (DMD) usually presents in early
childhood by delays in sitting and standing independently. Proximal
weakness causes a waddling gait and difficulty climbing. DMD is
rapidly progressive, with affected children being wheelchair
dependent by age 12 years. Cardiomyopathy occurs in individuals
with DMD after age 18 years. Few survive beyond the third decade,
with respiratory complications and cardiomyopathy being common
causes of death.
 Becker muscular dystrophy (BMD) is characterized by later-onset
skeletal muscle weakness; individuals move independently into their
20s. Despite the milder skeletal muscle involvement, heart failure
from DCMP is a common cause of morbidity and the most common
cause of death in BMD. Mean age of death is in the mid-50s.
Duchenn/Becker muscular dystrophy
X linked-dominant
 The pattern may at first glance be mistaken for AD
inheritance, but if offspring of affected males are
considered,all sons are unafected,all daughters are
affected
 Sometimes the disorder is seen only in the
heterozygous females, the affected(hemizygous)
males being undetected or appearing as an excess
of spontaneous abortion
 Fragile X syndrome
 Rett syndrome
Fragile X syndrome
 most common form of inherited mental retardation developmental
delay, variable levels of mental retardation,
and behavioral and emotional difficulties.
- characteristic physical traits-macrocephaly,coarse facies
,large forehead,long face,prominent jaw ,large ears.
Macroorchidism-postpubertal
 Generally, males are affected with moderate mental
retardation and females with mild mental retardation.
 FMR1 gene- FRAXA (Xq27.3)
 a trinucleotide (CGG)n repeat expansion of greater than 200
repeats.
Genetic risks in cancer
Cancer- genetic connection
The second most common cause of death
Every third person has risk of tumour
 80% sporadic cancers
 10% common cancers - familial
 5-10% - hereditary tumour syndromes
following mendelian inheritance
Hereditary tumour syndromes
 2 or more cases of occurrence in the family
 Particularly young age at onset
 Combination of certain types of cancer(breast and
ovarian cancer, uterine and colorectal ca)
 Any evidence of more then one of the rare tumour
in family
 Bilateral occurrence in paired organs
 Multiple cancers in a single individual
 Strong family history of a single form of cancer
 Mendelian inheritance, usually AD
Common cancers
 2 or more cases of occurrence in the
family
 Incidence in later life(older age)
 unclear inheritance (random
occurrence, environmental factors,
genetic factors - genes with low
penetrance, polygenic inheritance)
Familial tumour syndromes with
folloving AD inheritance- examples
 Breast cancer ( BRCA 1,2 )
 Lynch syndrome ( HNPCC) ( MMR genes,
MLH1, MSH2, PMS1, PMS2, MLH6)
 FAP ( APC gene)
 Li Fraumeni syndrome - P53 gene
 Von Hippel Lindau syndrome (VHL gene)
 MEN 1 a 2 (Ret oncogene)
 Retinoblastoma- ( Rb gene)
 Neurofibromatosis 1,2 - gene NF1,2
 Wilms´ tumour (WT1gene)
 Cowden disease (PTEN)
The Aim of genetic testing
 Is in the family genetic predisposition?
 To identify persons at risk
 To ensure molecular genetic testing as
possible
 Predictive testing of relatives at risk
 To ensure primary and secondary
prevention in cooperation with
oncologists and other specialists
Primary prevention
 Reduce pollutants- no smoking, alcohol…
 diet with reduced fat, meat, spicy dishes, sausages
 enough fiber, at least 4 to 5 portions of fruit and
vegetables a day
 stress prevention
 prevention of sunburn
 adequate physical activity
Secondary prevention
 Specific procedures for monitoring or
preventive treatments given at
different syndromes with regard to the
amount of risk and patient age
Hereditary Breast and Ovarian
Cancer Syndrome
 BRCA1, BRCA2
 High risks of breast and ovarian ca
 Other:carcinoma of the uterus,
prostate, stomach,colorectal, pancreas
 Secondary prevention: selfmonitoring,
UZ, mammography,NMR,tumor markers,
occult blood test, colonoscopy, gastroscopy,
mastectomy and ovariectomy
HNPCC-Lynch syndrome
 MMR genes, MLH1, MSH2, PMS1,
PMS2, MLH6)
 High risk of colorectal ca
 Other: ca of uterine, stomach,
liver, kidneys, brain tu
 Secondary prevention: colonoscopy,
gastroduodenoscopy, gynecology(vaginal
US), abdominal US, tu markers, urological
ex., MMG,
FAP
 APC gene
 Multiple adenomatous polyps
 Age: 7-35
 High risk of colorectal ca, other:
meduloblastoma, thyreoid
ca,hepatoblastoma, ca of pancreas,
stomach
 Secondary prevention: colonoscopy, gastroscopy,
protecticve bowel resection
Von Hippel-Lindau
syndrome
 Gene VHL
 Retinal hemangioblastomas,
hemangioblastomas of CNS, multiple
renal, pancreatic or hepatal cysts,
pheochromocytoma,
 Secondary prevention:
ophtalmology,neurology,endocrinology
, CT,NMR,US
Li-Fraumeni syndrome
 geneTP53
 breast cancer, soft tissue sarcoma,
osteosarcoma, brain tumors, adrenal
tumors, leukemia,melanoma, gastric,
pancreatic, colorectal ca, etc.
 Difficult prevention
Presymptomatic testing
 Specific
 Protocol procedures
 Up to 18 years (exception-FAP, MEN, VHL, Rb,WT, NF-where
can offer prevention in children)
 completely voluntary
 Genetic consultation before testing-meaning informed
consent, follow-up information
 Genetic consultation after notification of the result of testresulting
risks, prevention (surveillance, surgery,
chemoprevention)
 Transmission contact to specialist –doctors providing
preventive monitoring, including a psychologist
Problemes
 Ethical: we can not eliminate tumor formation
difficult prevention in some syndromes
 Psychological: high risks lifetime
high risks for children
division of family members on healthy x ill
 Social: risk of discrimination such as commercial insurers,
employers
Preconception counseling
 Birth control
 Monitoring of spontaneous
chromosomal aberrations
 cryopreservation of gametes
 monitoring risk pregnancies
 Prenatal diagnosis,
 IVF-PGD
Mitochondrial inheritance
 Mitochondrias are organelles found in the
cytoplasm of cells and they have multiple copies of
a circular chromosome- mitochondrial DNA
 Because only egg cells contribute mitochondria to
the developing embryo, only mothers can pass on
mitochondrial conditions to their children- maternal
inheritance
 The primary function of mitochondria is conversion
of molecule into usable energy. Thus many
diseases transmitted by mitochondrial inheritance
affect organs with high-energy use such as the
CNS,heart, skeletal muscle, liver, and kidneys.
Mitochondrial diseases
 Mitochondrial Myopathy,Encephalopathy
,Lactic acidosis and Stroke-like Episodes
MELAS
 Leber hereditary optic Neuropathy- LHON
 Myoclonic Epilepsy associeted with raggedred
Fibers- MERRF
 Neuropathy, Ataxia and Retinitis pigmentosa
NARP
Pedigree- not unusual
situation
Molecular genetic testing
 Detection of mutations
 Search asymptomatic carriers
 Prenatal diagnosis, PGD
 Predictive testing of diseases with onset
in adulthood
 Onkogenetic -diagnosis, predictive
testing
 Paternity and relationship testing
Diseases with a single
causative mutation
 Huntington disease
 Myotonic dystrophy
 Fragile X syndrome
 DNA analysis can confirm or
exclude disease
DNA diagnosis difficult
 Large genes
 Private-unique mutations
 disease with multiple genes responsible
Multifaktorial –polygenic
inheritance
Charakterization
 disease with multifactorial inheritance
includes not mendelian types of
inheritance
 diseases exhibit familial aggregation,
because the relatives of affected
individuals more likely than unrelated
people to carry diseases predisposing
genetic changes
Charakterization
 in the pathogenesis of the disease
play an important role non-genetic
factors
 disease is more common among
close relatives and in distant
relatives is becoming less frequent
 risk of recurrence can be determined
empirically
Empirical risk
 The risk of recurrence of the disease
observed in similar families and
relatives of the same degree of
kindship
Monogenic x multifactorial inheritance
Monogenic
 In early age
 No enviromental
influence
 Typicaly inheritance
patterns sometimes
according the gender
 High penetrance
 Low frequency
Multifactorial
 In later age
 Combination genetic
and enviromental
factors
 No typical patterns of
inheritance
 Incomplete penetrance
 High frequency
Examples
 Congenital heart defects (VCC) 4-8/1000
 Cleft lip and palate (CL/P) 1/1000
 Neural tube defects (NTD, anencephaly, spina
bifida,..) 0,2-1/1000
 Pylorostenosis
 Congenital hip dislocation
 Diabetes mellitus – most types
 Ischemic heart desease
 Esential epilepsy
Common congenital defects
Congenital heart defects
 Incidence-0,5 - 1% in liveborn infants
population
 etiology not known mostly
 about 3% - chromosomal syndromes
(+21,+13,+18, 45,X, 18q-, 4p-, del
22q11- DiGeorge sy)
 some mendelian syndromes associated
with congenital heart disease (HoltOram,
Williams, Noonan, Ivemark...
Congenital heart disease genetic
risks
condition 1 aff.
sibling
1 aff.
parent
Ventricular septal def. 3% 4%
Patent ductus art. 3% 4%
Atrial septal defect 2,5% 2,5%
Tetralogy of Fallot 2,5% 4%
Pulmonic stenosis 2% 3,5%
Koarctation of aorta 2% 2%
Congenital heart disease
genetic risks
Risk in %
More than two affected
firstdegree relatives
50
Sib of isolated case 2 - 3
Second-degree relatives 1 – 2
Offsprin- affected father 2 - 3
Offsprin – affected mother 5
Two affected sibs 10
Cleft lip and palate
 Population incidence CLP 1/500-1/1000
 Multifactorial mostly
 With chromosomal trisomies (+13,+18)
 Syndromes associated with CL/CP/CLP
 (van der Woude sy, EEC sy, Pierre
Robin sequence…)
 Prenatal diagnosis by ultrasonography
not sure
Cleft lip and palate- genetic
risks
Relationship to index case CLP CP
Sibs (overall risk) 4% 1,8%
Sib (no other affected) 2.2%
Sib(2 affected sibs) 10% 8%
Sib and parent affected 10%
Children 4,3% 3%
Second-degree relatives 0,6%
Neural tube defects
 Multifactorial inheritance (risk for I.
degree relatives about 2 - 4%)
 Maternal serum AFP screening
 Prenatal diagnosis by ultrasonography
 Raised AFP levels in amniotic fluid
 Primary prevention in pregnancies by
folic acid
 Risk populations - probably related to
nutritional status
Teratogens
Teratogens
 teratogen is a substance whose by
effect on embryo or fetus may cause
abnormal development
action may be direct or through the
maternal organism
Human Teratogens
 Physical (radiation, heat (fever),
mechanical impact)
 Chemical (chemicals, drugs)
 Biological (infectious agents...)
 Metabolic imbalance (disease mother)
The effect of teratogens depends on :
 dose
 length of the action
 contact time
 genetic equipment of the fetus and
the mother
Critical period
 14.-18. day after conception – the rule
„all or nothing “
 18.-90. day – organogenesis
 The most sensitive period for the
emergence of developmental defects
 between 5. to 7. week of pregnancy is the
most sensitive period for individual organs
Critical periods
 3th to 6th week - CNS, heart
4th to 7th week - limbs and eyes
6th to 8th week - teeth
late 6th - to 12th week – palate
7th-12th week - external genitalia
4th to 12th week - ears
X-ray
 mutagenic effect
teratogenic effects
 growth retardation, major congenital
malformations ,fetal death
border dose - 0.6 Gy
teratogenic dose - 2.0 Gy
conventional X-ray examination. dose of 0.01 Gy
 calculation of radiation doses-Institute
of Nuclear safety
Drugs
 Distribution of medicines in
practice into categories
 A
 B
 C
 D
 X
 Food and Drug Administration, 1980
A
 in controlled studies have shown no
evidence of risk to the fetus in
the first trimester of fetal
development or influence in the
next period of pregnancy
product appears to be safe
B
 Animal reproduction studies have
shown adverse effect, but in
controlled studies in women it have
not been confirmed
product appears to be relatively
safe
C
 Animal studies confirm the teratogenic
embryotoxic or other adverse effects on the
fetus,
 non-controlled studies in women
 lack of studies in animals and humans
The product should be administered with
caution and only in cases where the benefit
for the woman of its administration exceeds
the potential risk to the fetus
D
 risk to the human fetus is known
 medicine may be administered in a
situation where its use for a
woman needed (lifesaving)
 no other safer drug is available
X
 studies in animals and in humans
clearly demonstrate a teratogenic
effect
 drugs absolutely contraindicated in
pregnancy
Drugs with teratogenic effect
 Thalidomid
 Hydantoin
 Valproic acid
 Anti coagulans - Warfarin
 Trimetadion
 Aminopterin
 Methotrexat
 Cyklophosphamid
Drugs with teratogenic effect
 Retinoids
 Lithium
 Thyreostatic drugs
 Androgens
 Penicilamin
 Enelapril, Captopril
 Antituberkulotics-Streptomycin
Thalidomide
 congenital heart defects
 limb reduction anomalies
 Other congenital defects
(gastrointestinal, urogenital tract
orofacial – ears anomalies, CNS
defects..)
Hydantoins
 are used to treat a wide range of seizures
types.
 Atypicaly face, growth retardation, mild
mental retardation, behavioral problems,
hypoplastic nails and fingers
Aminopterin a Methotrexat
 folic acid antagonist
facial dysmorphias, cleft lip and/or
palate, small mandible, ears
anomalies, hydrocephaly, growth
and mental retardation,
miscarriages
Warfarin
 coumarin antikoagulans
 facial dysmorphias – nasal cartilage
hypoplasia, CNS - defects
Retinoids
 Cleft lip and palate, mikrognatia, eyes
anomalies, ears dysplasia
 Defects of CNS
 Thymus hypoplasia
 Limb defects
Infection
 Toxoplasmosis
 Rubella
 Cytomegalovirus
 Herpesvirus
 Others (parvovirus, antropozoonosis,
chlamydia..)
 TORCH
Consequences of
Infections
 direct infection of the fetus and its consequences
 infection of the placenta-failure of the exchange of
oxygen and nutrients
 prolonged high fever mother may affect fetal
development, even without direct infection
 infection of the membranes can cause premature
labor or miscarriage otherwise healthy fetus
 Some developmental disorders can cause by
infection treatment
Toxoplasmosis
 chorioretinitis
 hydrocephaly or microcephaly
 intracranial calcification, mental retardation
 icterus, hepatosplenomegalia, carditis
 prematurity
 positiv IgM in the mother – treatment with
Rovamycin
 Prenatal dg.: serology, DNA-PCR
Rubella
 hearing and vision impairment (cataract,
glaucoma, mikroftalmia, blidness)
 mental retardation
 Cong. heart defects
 icterus, hepatosplenomegalia
 prevention- vaccination
Cytomegalovirus
 Intrauterin growth retardation
 mikrocephaly, cacification in the
brain, mental retardation,
 hepatosplenomegaly
 Repeated maternal infection is
possible
 Prenatal dg.: serology,DNA-PCR
Varicella zoster
 Skin lesions and defects
 Brain damage, mental retardation
 Eye defects
 Prenatal dg. - serology, DNA-PCR
Metabolic dysbalance
 Fetal alcohol syndrome (FAS)
 Maternal Phenylketonuria
 Maternal Diabetes mellitus
 Maternal Hypothyreosis
Fetal alcohol syndrom
 Hypotrophy, growth retardation, mental
retardation
 facial dysmorphism
 Congenital heart defects
 Limb defects
 Abuse of 60g pure alcohol / day
(longterm)
 Combine with malnutrition, folic acid
deficiency, inadequate health care...
Maternal Phenylketonuria
 Low birth weith
 hypertonia
 mikrocefaly, mental retardation
 Cong. heart defects
 hyperaktivity
Diabetes mellitus
 risk of congenital malformations to the
fetus 2-3x higher
CNS - anencephaly, microcephaly
cardiovascular and genitourinary
anomalies
skelet - caudal regression syndrome
face - cleft palate, eye involvement
Prevention - preconception
compensation
Hypothyreosis
 coarse facial features, macroglossia,
inverted nose
brachycephalia
dry skin, sleepiness, constipation
delayed bone maturation, short stature,
oligophrenia, hearing loss, disruption hips
(duck walk)
 Hyperthyreosis - rather risk SA
Genetic consulting
 Primary prevention (pre-conception advice,
based on the history of an optimal
procedure)
 Secondary prevention (to adjust therapy
during pregnancy, to ensure specific
prenatal. diagnosis)
Extreme solutions – possibility of medical
termination of pregnancy
Medical termination of pregnancy
 until the end of 24th. week of
pregnancy in Czech Republic- of law
 (governed by the Act and the Decree
of the Ministry of Health in CR)
 It indicates only a clinical geneticist!