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GENETICS, PERINATAL AND PAEDIATRICS - Coggle Diagram
GENETICS, PERINATAL AND PAEDIATRICS
GENETIC DISORDERS
NUMERICAL CHROMOSOME DISORDERS
MONOSOMY
Turner Syndrome (45, X)
due to anaphase lag during gametogenesis or early after fertilisation
clinical symptoms are due to haploinsufficiency
TRISOMY
Trisomy 13 - Patau syndrome
severe facial malformations - microphthalmia, cleft lip and palate
Trisomy 18 - Edward syndrome
rocker bottom feet
serious congential malformations
Trisomy 21 - Downs syndrome (47, XX/XY, +21)
over the age of 40, pathological changes characteristic of Alzheimer's can occur
possibly due to increased gene dosage of the amyloid precursor protein (APP)
recurrence risk for future pregnancies is increased
mainly due to non-disjunction, but can also be due to robertsonian translocation or mosaicsim
non-dysjunction carries a recurrence risk of 1%
robertsonian translocation carries a recurrence risk of 2.5% if the father is a carrier and 10% if the mother is a carrier
karyotype is carries out to confirm diagnosis and establish aetiology
a disorder of gene dosage and genes on chromosome 21 that are dose sensitive
prenatal screening for down syndrome has an 85% detection rate in the first trimester using chorionic villus sampling
prenetal screenign can also be done in the second trimester using amniocentesis, or PCR
Klinefelter syndrome (47, XXY)
males have 1 barr body
usually relatively asymptomatic with diagnosis because of infertility
Numerical errors are due to errors in fertilisation or cell division
SINGLE GENE DISORDERS
mutations
missense point mutation - a single nucleotide base change that results in different amino acids being formed e.g. sickle cell anaemia
nonsense point mutation - single nucleotide base change that results in a premature stop codon e.g. beta-thalassaemia
framesgift insertion/deletion - extra/missing bases that is not a multiple of 3 e.g. 35delG in connexin 26, a common cause of autosomal recessive congenital deafness
non-frameshift insertion/deletion - extra/missing bases that is a multiple of 3 e.g deltaF508 deletion, a common CF allele
autosomal inheritance
dominant - this is a disorder that is expressed ina heterozygote, i.e. a single mutant allele is sufficient to produce the disorder
an affected child usually has an affected parent
approximately half the children of an affected parent will be affected and the risk for each pregnancy is 1 in 2
both sexes are equally affected and can transmit the condition
examples:
Familial Hypercholesterolemia
formation of xanthomas (cholesterol deposits) in skin and tendons
haploinsufficiency of the LDL receptor leading to defective clearance of low density lipoprotein
LDL receptor gene on chromosome 19p
Marfan Syndrome
pleiotropic connective tissue dissorder that affects multiple areas within the body
clinical features include tall, long limbs, arachnodactyly, scoliosis, lens dislocation, risk of mitral prolapse/aortic dissection
FBN! gene on chromosome 15q that codes for fibrillin
most mutations are missense
15% of Marfan cases are due to spontaenoues de novo mutations
Achondroplasia
large head with prominent forehead and shortened limbs
80% of cases are spontaenous de novo mutations
missense mutation is in the fibroblast growth receptor 3 (FGFR3) gene on chromosome 4p
gain of function mutation
inhibition of cartilage proliferation and chondrocyte growth
Neurofibromastosis type 1
100% penetrance but has variable expressivity
clinical features include multiple neurofibromas dispersed anywhere on or in the body, distinct cafe au lait spots, and pigmented iris hamartomas (Lisch nodules)
NF-1 is a tumour suppressor gene on chromosome 17
complications in AD inheritance
penetrance - the probability that a gene will have phenotypic expression, i.e. there can be skipped generations
variable expressivity - severity of a disease is not constant
anticipation - this is where the severity of a disease increases over egenrations
mosaicism - this is where the ratio of mutatn to normal alleles alters severity
recessive - a disorder that is only expressed in a homozygote for the mutant allele, in a heterozygote the normal allele masks the effect of the mutatn allele
features:
disease is only expressed when a mutated allele is received from each parent
there is equal frequency and severity in both sexes
usually consist of disorders that affect metabolic pathways
children with a rare autosomal recessive disorder are more likely to have related parents - consanguinity
examples:
Cystic Fibrosis
disorder in epithelial transport affecting fluid secretion in exocrine glands and the epithelial lining of the respiratory, gastrointestinal, and reproductive tracts which leads to abnormally viscid secretions, obstructing organs
10% present at birth with an intestinal obstruction - meconium ileus
pancreatic insufficiency
chronic lung disease with recurrent pulmonary infections
most males are infertile
diagnosis is through molecular testing, newborn screening, and the sweat test
possible Kalydeco treatment for G551D mutations
mutation in the CFTR gene on chromosome 7q, which normally is an ion channel that regulates lipid volume on epithelial surfaces through chloride secretion and inhibition of sodium absorption
Phenylketonuria
disorder of amino acid metabolism
clinical signs include hyperactivity, irritability, voluntary purposeless repetitive motions
screened for here with Guthrie's heel prick test
mutation in the gene coding for phenylalanine hydroxylase (PAH) on chromosome 12
Hereditary Haemochromatosis
iron storage disease characterised by excessive accumulation of iron from the diet with consequent tissue injury and irreversible organ damage
type 1 HH often due to mutations in the HFE gene on chromosome 6p
majority of cases are homozygous for the C282Y missense mutation in exon 4, or the H6eD mutation less commonly
if a condition is truly dominant, there is equal severity in the homo and heterozygous case but most are no like this
pseudodominance is where the inheritance of an AR condition mimics an AD pattern
50% of offspring are affected possibly due to one heterozygous and one homozygous parent, loss of genetic material, or deletion and deficiency mutations
Sex-linked Inheritance
X-Linked recessive inheritance
features:
disorders are more common in males
diseases are transmitted by phenotypically normal heterozygous females to their sons
an unaffected male does not transmit the disorder
affected males pass the mutatn gene on to all of their daughters and none of their sons
carrier females have a 50% chance of an affected son and a 50% chance of a carrier daughter
examples:
Duchenne Muscular Dystrophy
early onset (<5years)
progressive proximal muscle wasting with calf pseudohypertrophy
delayed walking and Gower's sign
wheelchair bound by 10years, bedridden by 15, and death usually occurs by early 20s from respiratory or cardiac failure
biomarker can show an increase in cretine kinase
PCR/FISH are used to confirm diagnosis and identify carriers and prenatal risk
mutations are seen in the dystrophin gene on chromosome Xp
Becker's Muscular Dystrophy
milder related ford of duchenne muscular dystophy, with same muscle groups affected
later onset (>11yrs), slower progression, less severe calf pseudohypertrophy
chair bound by 25, but usally live into their 50s
MULTI-FACTORIAL GENETIC DISORDERS
conditions that show familial clustering that does not fit with mendelian inheritance
to determine nature vs nurture, we use Family studies, adoption studies, and twin studies
factors affecting recurrence risk
increased amongst close relatives of the index case
increased if multiple family members are affected
increased with increased severity of the defect
increased if the index case is of the lesser affected sex
examples of congenital malformations that are multifactorial disorders
cleft lip and palate
club foot
neural tube defects
congenital dislocated hip
pyloric stenosis
congenital heart disease
examples of common adult diseases that are multifactorial disorders
diabetes
type 1 has a strong association with the human leukocyte antigen (HLA) loci on chromosome 6 and the majority have HLA DR3 and/or HLA DR4
coronary heart disease
epilepsy
hypertension
mental retardation
schizophrenia
alcoholism
manic depression
late onset familial alzheimer disease shows an associated with the apolipoprotein E (apoE) encoded byt the APOE gene on chromosome 19 that plays a central role in cholesterol transport
STRUCTURAL CHROMOSOMAL ABNORMALITIES
Structual abnomalities are due to breakage, either at a characteristically fragile point, or a random break point
MUTATIONS
LOSS OF FUNCTION MUTATIONS
GAIN OF FUNCTION MUTATIONS
HAPLOINSUFFICIENCY
MITOCHONDRIAL INHERITANCE
TRINUCLEOTIDE EXPANSION DISORDERS
Huntington's disease
autosomal dominant
late onset, but more repeats means earlier onset
100% penetrance and is ultimately fatal
physical symptoms include changes in coordination, involuntary movement, prolonged muscular contraction of face, neck and back, trouble with blanace and walking, bradykinesia, serious weight loss, and the inability to walk, speak, or swallow
mental symptoms include aggression, anxiety, apathy, depression, and issues with memory, awareness, and communication
features an expansion in the CAG repeat in exon 1 of the Huntingtin gene (HTT) on chromosome 4p
more than 35 copies shows increased risk (premutation), and more than 40 copies of the CAG repeat results in full penetrance
Myotonic Dystrophy
(DM1)
autosomal dominant disorder that usually presents in adults but severe congenital forms can occur also
symtpoms:
difficulty in relaxing contracted muscles
muscle wasting and weakness
facial muscle weakness that can result in an expressionless face
endocrine changes can lead to cataracts, hypogonadism and frontal baldness in males
mental deterioration
cardiac arrhythmia
mutation is through CTG expansion in the myotonin kinase (DMPK) on chromosome 19q
the CUG repeat results in the interference with normal splicing
DM2 is clinically very similar to DM1 but does not have a congenital form
mutation is teranucleotide repeat (CCTG) in the ZNF9 gene of intron 1 on chromosome 3q
Fragile X Syndrome
most common cause of inherited mental retardation
expansion CGG repeat (>200 copies) on the FMR1 gene of the X chromosome associated with hypermethylation of DNA and gene splicing
symptoms result from improper protein translation in neurons due to a lack of FMRP
it involves atypical inheritance
Sherman paradox - pattern is not consistent with X-linked recessive disorders
risk increases with each generation
males can carry and transmit the disease
it was then discovered that the gene has to undergo 2 seperate mutations, a premutation and full mutation, for clinical symptoms to appear
clinical features:
males have very low IQs, macro-orchidism, are tall with a large head, long face, and prominent ears
females are more likely to have behavioural changes such as shyness and poor eye contact
most common single gene cause of autism spectrum disorders
fragile X premutation carrier phenotypes: due to a toxic gain of function mechanism in carriers of the premutation
premature ovarian failure
fragile X associated tremor and ataxia (FXTAS syn.)
DISORDERS OF GENOMIC IMPRINTING
Prader-Willi Syndrome / Angelman Syndrome
On chromosome 15q, the maternal copy of the SNRPN gene is imprinted, so if the paternal copy is deleted, the child will have Prader-Willi syndrome
On chromosome 15q, the paternal copy of the UBE3A gene is imprinted (silenced), and so if the maternal copy is deleted, the child will have Angelman syndrome
PWS features: hypotonia, mental retardation, polyphagia, hypogonadism and obesity
AS features:severe mental retardation, movement disorder, seizures, paroxysmal laughter, microcephaly and absent speech
Beckwith Wiedemann Syndrome / Sporadic Syndrome
overgrowth
macroglossia
visceromegaly
exomphalos (large hole in the abdomen)
hemi hypertrophy
ear creases
omphalocoele (umbilical hernia)
hypoglycemia
1000x increased risk of childhood tumours e.g. Wilm's
caused by paternal trisomy of Chr 11p15.5 region, paternal unipaternal disomy of chromosome 11, paternal duplication of Chr11p15.5 region, or translocations/mutations involving the maternal 11p15.5
PERINATAL AND PAEDIATRIC DISORDERS
PATHOLOGY OF PREGNANCY
specific to pregnancy:
Early pregnancy disorders:
spontaneous abortion/miscarraige
fetal causes:
defective implantation
genetic abnormalities e.g. aneuploidy, trisomy 18, trisomy 16
acquired e.g. TORCH infection, mycoplasma, listeria
maternal causes: (less understood)
inflammatory disease
uterine abnormalities
possibly trauma, although this is rare
ectopic pregnancy (commonest site is the fallopian tube)
predisposing conditions
pelvic inflammatory disease
peritubal adhesions
endometriosis
tubal ligation
clinical features
sever abdominal pain at approximately 6 weeks
cardiovascular shock - a medical emergency
diagnosis:
serum beta hCG
ultrasound scan
laparotomy/laparoscopy
treatment:
surgical
medical - methotrexate (although rare)
gestational trophoblastic disease (Molar pregnancy)
complete hyatidiform mole
women present with:
uterus large for corresponding pregnancy dates
hyperemesis
1st trimester vaginal bleeding
symtpoms of thyrotoxicosis
theca lutein cysts
partial hydatidiform mole
triploid karyotype
choriocarcinoma
responds well to chemotherapy
presents with PV spotting
markedly elevated levels of beta hCG
features widespread metastasis
Late Pregnancy disorders
disorders of placentation
disorders of implantation
placenta praevia
implantation of the placenta over the internal cervical os
risk factors: prior c-section, pregnancy termination, intrauterine surgery, smoking, multiple births, increased age
complications: abnormal lie, antepartum haemorrhage, difficulty in delivery, postpartum haemorrhage, DIC, foetal exsanguination
placenta creta (accreta/percreta)
chorionic villi are immediately adjacent to or penetrate the myometrium to a varying degree
main risk is antenatal and postnatal bleeding
disorders of seperation
placental abruption/RPH
complications:
antepartum haemorrhage
uterine rupture
disseminated intravascular coagulation
foetal demise
clinical presentation:
bleeding
abdominal pain
hard uterus on palpatation
placental inflammation (due to TORCH infections)
villitis
chorioamnionitis
placental vascular disorders
fetal artery thombosis
placental infarct
haemangioma
pre-eclampsia/eclampsia
PET is characterised by hypertension, proteinuria and oedema
usually occurs in the last trimester and in primiparous women
caused by placental ischaemia and decreased uteroplacental perfusion induces stimulation of vasoconstrictor substances and inhibits vasodilator substances
induction and delivery is the only treatment for established PET or eclampsia
complications of PET:
Eclampsia - CNS involvement with convulsions and eventual coma
HELLP syndrome - Haemolysis, Elevated Liver snzymes, Low platelets
IUGR - intra-uterine growth restriction
amniotic fluid embolism
characterised by:
sudden, severe, shortness of breath
cyanosis
hypotensive shock followed by seizures and a coma
classic findings:
foetal squamous cells
mucin
vernix caseosa
lanugo hair
complication of labour and immediate postpartum caused by amniotic infusion into the maternal circulation
conditions exacerbated by pregnancy:
thrombo-embolic disease
leading cause of maternal mortality
pregnancy is itself a hypercoaguable state
commonly seen in the peurperium
increased risk after caesarean section
malignancies
all chemotherapeutic drugs cross the placenta
breast cancer > Hodgkin's Lymphoma > Melanomas > Cervical Carcinoma
auto-immune diseases
in general, we see an improvement in symptoms
SLE is associated with an increased incidence of miscarraige and pregnancy can cause a flare-up but is usually not severe
cardiac diseases
onset of cardiac failure with no identifiable cause
associated with older mums, multiple gestations, people of colour, prolonged use of tocolytics
high mortality within two weeks of delivery
aortic dissection, rare but associated with PET, coarctation or Marfan's syndrome
TERATOGENESIS
types of abnormalities that result from teratogen exposure
malformation - anomaly during structure formation e.g. cleft palate
disruption - alteration of already formed structures e.g. amniotic bands
deformation - mechanical forces acting on formed structures e.g. club foot
syndrome - spectrum of anomalies resulting from a common cause e.g. fetal alcohol syndrome
association - apectrum of anomalies from an unknown cause that frequently occur together
known teratogens
drugs
alcohol
fetal alcohol syndrome - affects neurodevelopment, growth, and craniofacial formation
thalidomide
foilc acid
retinoic acid
anticonvulsants e.g valproic acid can cause fetal valproate syndrome - this can induce facial malformations, spina bifida, low IQ, autism
anti-cancer agents e.g. methotrexate can terminate early stage pregnancy
anticoagulants e.g. warfarin can cause fetal warfarin syndrome
chemicals
mercury
Minamata disease
lead
polychlorinated biphenyls (in collants)
pesticides
physical agents
ionising radiation
hyperthermia
metabolic conditions
diabetes
obesity
phenylketonuria
thyroid disease
infection
rubella
cytomegalovirus
varicella zoster virus
herpes simplex
toxoplasma gondii
treponema pallidum
zika virus
SARS-CoV-2
PERINATAL PATHOLOGY
PREMATURITY
Risk factors for prematurity:
hypertension
maternal age extremes
short cervix
uterine malformations
maternal diabetes
infection
previous history
multiple pregnancies
tobacco and alcohol/illegal drugs
pre-eclampsia
Complications of prematurity:
neurological
apnoea of prematurity
hypoxic ischaemic encephalopathy
intracranial haemorrhage
retionpathy of prematurity
dvelopmental disability
cardiovascular
patent ductus arteriosus
respiratory
respiratory distress syndrome - the leading cause of morbidity and mortality in premature infants
lining cells of fetal alveoli do not differentiate into type I and type II pneumocytes until late pregnancy
when surfactant is inadequate, alveoli collapse on exhalation and resist expansion on a second breath
hypoxia can occur as a result
prevention using antenatal maternal glucocorticoids
bronchopulmonary dysplasia
due to oxygen toxicity superimposed upon respiratory distress syndrome
gastrointestinal/metabolic
hypoglycaemia
feeding difficulties
rickets of prematurity
hypocalcaemia
inguinal hernia
necrotising enterocolitis
possibly due to ischaemia of the intestinal mucosa and subsequent bacterial colonisation
haematologic
anaemia of prematurity
thrombocytopaenia
jaundice
liver immaturity results in deficiency in glucuronyl transferase resulting in unconjugated bilirubin that can cross the BBB and can injure the brain by interfering with mitochondrial function and kernicterus (loss of startle reflex and development of atheroid movements
treatment is with phototherapy, or in extreme cases, exchange transfusion
infectious
FETAL GROWTH RESTRICTIONS
causes of IUGR
disorders impairing maternal health and nutrition
disorders interfering with placental circulation and function
disorders that disturb the growth and development of the foetus
symmetrical fetal growth restriction is where the foetus has developed slowly throughtout pregnancy and their head circumference is in proportion to the rest of the body
assymmetrical fetal growth restriction is where the foetus has grown normally for the first two trimesters but encounters difficult in the third, resulting in a disparity in their length and head circumference when compared to birth weight
BIRTH INJURIES
common injuries:
clavicular fracture
facial nerve injury
brachial plexus injury
intracranial injury - intracranial haemorrhage is the most common important birth injury
humeral fracture and lacerations
CONGENITAL ABNORMALITIES
causes:
sporadic
genetic - chromosomal abnormalities or single gene mutations
envrionmental - teratogens (viruses, drugs and chemicals, irradiation)
multifactorial - complex interaction between mutliple minor genetic abnormalities with environmental risk factors
RHESUS DISEASE OF THE NEWBORN
hydrops fetalis is where there is oedema of the foetus and this can be divided into immune hydrops (Rhesus disease) and non immune hydrops
Rhesus disease severity ranges from mild haemolysis to fatal anaemia, and in utero death or kernicterus encephalopathy can also occur
treatment is usually through phottherapy and exchange transfusions to help keep the maximum serum bilirubin levels at an acceptable level
can be prevented with the administation of human anti-D immunoglobulin within 72 hours of delivery
INFECTIONS
transcervical (ascending) perinatal infections
mainly bacteria
acquired in utero
leads to pneumonia, sepsis and meningitis
transplacental (haematogenous) perinatal infections
mostly parasites and viruses
access the foetal blood stream via chorionic villi
occur any time during gestation or at delivery
PERINATAL MORTALITY
NEWBORN SCREENING
Irish newborn screening programme disorders:
Phenylketonuria
Classic homocysteinuria
Maple Syrup urine disease
Classical galactosaemia
hypothyroidism
Cystic Fibrosis
Glutaric aciduria type I
Medium Chain Acyl-Co-A dehydrogenase
adenosine deaminase severe combined immunodeficiency
CONGENITAL INFECTIONS
most common cause is primary maternal infection during the pregnancy
TORCH congential infections
Toxoplasma gondii
protozoal infection usually acquired from eating inadequately cooked meat, contaminated foods or contact with infected cat faeces
classical triad at birth: hydrocephalus, chorioretinits, intracranial calcification
Others e.g. Parvovirus, Varicells, Syphilis, Zika virus
Parvovirus B19 aka slapped cheek syndrome, can result in miscarraige during the first trimester or profound anaemia and hydrops fetalis if infection occurs during the second trimester
Zika virus with microcephaly, and other cerebral, ocular and neurological anomalies and contractures
Rubella
Cytomegalovirus
most common congenital infection
Herpes simplex virus (although usually perinatal infection)
results of congenital infections:
foetal loss - spontaenous miscarraige or stillbirth
intrauterine growth retardation
fetal anomalies
long term consequences despite infection not being apparent at birth
Prevention of Congenital Infection:
ANTENATAL SCREENING
universal (rubella, HIV, Hep B, syphillis) and targeted (TORCH screen)
VACCINATION
Rubella vaccination given before pregnancy or after delivery, hepatitis B vaccination, Varicella vaccination
ANTIMICROBIAL AND IMMUNOGLOBULIN TREATMENT
syphilis, toxoplasma, varicella, CMV
FOOD SAFETY
prevention of toxoplasmosis
MOSQUITO PROTECTION
ZIKA
SEXUAL PROTECTION
STIs and Zika
SUDDEN INFANT DEATH SYNDROME
Explained sudden infant death:
upper airway obstruction - petechiae on the surface of lungs
myocarditis
congenital aortic stenosis
endocardial fibroelastosis
anomalous origin of the left coronary artery
primary hypertrophic cardiomyopathy
tuberous sclerosis with cardiac rhabdomyomas
long QT syndrome
Histiocytoid cardiomyopathy
congenital heart block
arrhythmogenic right ventricular dysplasia
non-compaction of the left ventricle
respiratory - pneumonia/bronchiolitis
metabolic disorders - MCAD
Current risk factors for SIDS:
smoking environment
sleeping environment
overheating/overwrapping
prone sleeping
any illness since birth
blunted arousal system in the infant
Triple risk theory/model:
vulnerable infant
critical time in development
environmental stress
Non-accidental injury (Shaken Baby)
Pathology findings:
acute encephalitis and cerebral oedema
subdural haemorrhage
retinal haemorrhage
diffuse axonal injury in CNS white matter
inappropriate history
other injuries e.g. old fractures
diseases that can mimic NAI:
accidental injury
osteogenesis imperfecta
transient osteoporosis
rickets
reduced sensation
birth trauma
menkes
normal variants
HEREDITARY METABOLIC DISORDERS
Classification of inborn errors of metabolism:
COMPLEX MOLECULES
distrurbances in synthesis or catabolism of complex molecules
examples: fatty acid disorders, glycogen storage diseases, ketogenesis defects, mitochondrial disorders
diagnosis with enzyme assays, substrate measurement, and molecular analysis
treatment involves enzyme replacement therapy, chaperones, substrate reduction
ENERGY DEFICIENCY
deficiency in energy production or utilisation
examples: lysosomal/peroxismal disorders, cholesterol synthesis defects, congenital disorders of glycosylation
INTOXICATION
acute progressive accumulation of toxic compounds
examples: aminoacidopathies, urea cycle defects, maple syrup urine disease, organic acidurias
clinical signs of intoxication:
acute: reduced GCS, vomiting, liver failure, DVTs/Strokes
chronic: developmental delay/intellectual disability
treatment:
toxin removal through dietary manipulation, medication, dialysis
when do we investigate?
children of any age with unexplained encephalopathy - dysmorphic features
progressive neurological disease
acid/base imbalance or hypoglycaemia
confirmed lactic acidosis
unexplained multi organ disease
diagnostic tests for infant with suspected IEM
FBC
urinalysis
blood gas
serum electrolytes
blood glucoseplasma ammonia
urine ketones
urine organic acids
plasma amino acids
plasm lactate or lactate profiling
acylcarnitine profile
CHILDHOOD INFECTIONS
causes of maculopapular rash:
measles
highly infectious systemic infection through airborne or contact transmission
clinical features:
incubation period 8-13 days
high fever, cough, conjunctival inflammation, runny nose
koplik's spots
rash that appears on day 3-4 of illness and starts at the hariline behind the ears and then spreads down the body and begins to fade within a week
complications:
secondary bacterial complications - otitis media, pneumonia
post measles acute encephalitis
death from respiratory and neurological complications
sub-acute sclerosing panencephalitis
rubella
moderately infectious systemic viral infection with rash that is spread via droplets and direct contact
clinical presentation:
IP = 14-23 days
mild fever
rash appears on day 2-3
lymphadenopathy
older patients can have arthralgia
complications
congenital infection
thrombocytopenic purpura
encephalitis
parvovirus B19
infectious systemic viral infection aka slapped cheek syndrome and is transmitted from person to person through respiratory droplets and direct contact
clinical manifestations:
IP= 1-3 weeks
mild fever
rash initially on face and then reticular rash appears on body as the facial rash disappears
arthralgia - more common in adults
complications:
can result in aplastic crisis - in patients with preexisting haematologic abnormality
congenital infection
scarlet fever (streptococcus pyogenes)
rash appears 1-2 days after initial pharyngitis
human herpes virus 6 (roseola)
causes of vesicular rashes
varicella (chicken pox)
fluid filled vesicles, itchy, rash appears in crops
patient is infectious until all lesions have crusted
complications:
pneumonia
congential and perinatal infections
Shingles - reactivation of varicella infection that does not cross midline
herpes simplex
gingivostomatitis
others - hand, foot and mouth
enteroviruses - coxsackie viruses and echo viruses
mumps
complications:
CNS effects - aseptic meningitis and encephalitis
orchitis
pancreatitis
respiratory tract infections of childhood:
bacterial
pertussis - whooping cough
features paroxysms of coughing
complications:
cyanosis and apnoeic attackes
intracranial haemorrhages
secondary bacterial pneumonia
aspiration pneumonia
bordetella pertussis
epiglottitis
haemophilus influenza type b
viral
bronchiolitis
caused by respiratory syncitial virus
features significant mortality with preterm infants, chronic lung disease, and congenital heart disease
croup
parainfluenzae viruses 1, 2 or 3
IMMUNISATION
types of antigens: T cell dependent and T cell independent antigens
T cell dependent show long term immunity and a booster response
Vaccines in current use:
PERTUSSIS
acellular vaccine
whole-cell pertussis vaccine
POLIOMYELITIS
liver oral polio vaccine
inactivated polio vaccine
HAEMOPHILUS INFLUENZAE TYPE B
MMR VACCINE
PNEUMOCOCCAL VACCINE
polysaccharide pneumococcal vaccine
pneumococcal conjugate vaccine
INFLUENZA
inactivated whole virus vaccine
subvirion or split-virus vaccine
surface antigen vaccine
HEPATITIS B VACCINE (PEP)
BCG
live attenuated strain derived from Mycobacterium bovis and is most consistently effective against tuberculous meningitis and miliary tuberculosis
HPV
COVID-19
EBOLA
MOLECULAR DIAGNOSTIC TECHNIQUES
TOOLS OF MOLECULAR GENETICS
POLYMERASE CHAIN REACTION
SEQUENCING
HYBRIDISATION
MOLECULAR AND CYTOGENIC DIAGNOSIS
CYTOGENETICS
GENOMICS IN MEDICINE
GENETIC COUNSELLING
INTRODUCTION TO GENETIC COUNSELLING