Genetically Inherited Diseases Flashcards
What are the three points of the etiology triangle of disease?
100% environmental
Single gene
Polygenic
What are some diseases typically associated with genes?
Duchenne Muscular Dystrophy
Haemophilia
Osteogenesis imperfecta
What are some diseases typically associated with the environment?
Tuberculosis and Scurvy
What are some diseases typically associated with both genes and the environment?
Spina bifida
Pyloric stenosis
What are some features of more genetic diseases?
Unifactorial
Rare
Mendelian - so high recurrence rate
What are some features of more environmental diseases?
Still genes involved but more polygenic
Multifactorial
Common
Low recurrence rate
What does it mean if a disease is multifactorial?
Caused by genes and the environment (drugs, infections) - variation in genes causing alteration of function - one organ system affected
What does it mean if a disease is single gene?
One mutation - normally loss of function - dominant/recessive pedigree patterns - can affect structural proteins, enzymes, receptors and transcription factors
What does it mean if a disease is chromosomal
Whole stretched of genome deleted (thousands of genes involved) (can be seen with cytogenically down a microscope) - chromosomal imbalance which causes alteration in gene dosage - affects multiple organ systems affected at multiple stages in gestation; can be inherited in rare cases
What does it mean if a disease is mitochondrial?
Mutation in the mitochondrial DNA
What does it mean if a disease is germline?
Still single cell mutations but more infrequent - sporadic mutations in onca and tumour genes
What are some of the impacts of childhood genetic disorders?
50% deafness/blindness/sever MR
25% in patient visits
40-50% deaths
What are some of the impacts of adult genetic disorders?
5% disorders/diseases
10% common cancers
Describe how metaphase spread works?
Stained with giesma
Dark region show dense bunched up DNA
Pale regions show less condensed DNA
What are acrocentric chromosomes?
P arm is much smaller than Q arm
What is a syndrome?
A disorder with a collection of features
What causes Down’s syndrome?
Trisomy of chromosome 21
What are some of the collective features of Down’s syndrome?
Round face Protruding tongue Up-slanting palpebral fissures Epicanthic folds of eye Developmental delay
How can Down’s syndrome be diagnosed?
Can be diagnosed in utro prenatally so is screened for in pregnancy
What features can be seen on the ultrasound?
Short femurs Nuchal translucency Echogenic bowel Choroid plexus cyst Sandal gap, single palmar crease
What are the three different patterns of chromosomes that can cause Down’s syndrome?
- 95% people have three separate copies of chromosome 21
- 4% have extra copy of chromosome 21 because of Robertsonian translocation
- 1% have mosaicism with normal and trisomy 21 cell lines (and usually have much milder features because of the presence of normal cells) – occurs post zygotically
What causes Patau syndrome?
Trisomy of chromosome 13
Compare Patau syndrome to Down’s syndrome
More severe
What are some collective features of Patau syndrome?
Affects midline structures: Incomplete lobation of the brain Cleft palate Congenital heart disease (arterial septal defect) Inguinal hernia Postaxial polydactyly
What is the prognosis for Patau syndrome?
Poor prognosis - majority of babies die within first few weeks of life; if baby survives severe mental retardation
Why do trisomies occur?
When there is no disjunction (correct segregation) in meiosis, disomic and nullisomic gametes are formed. If a disomic gamete was to fuse with a monosomic gamete (spermatocyte and oocyte) a trisomy would form.
What are numerical chromosome abnormalities?
Gain or loss of complete chromosomes
What are the results of numerical chromosome abnormalities?
Serious, often lethal consequences (particularly autosomal) - MCA/MR syndromes
Name four microdeletion syndromes
DiGeorge syndrome
William’s syndrome
Prader-Willi syndrome
Cat Eye Syndrome
What causes DiGeorge Syndrome?
22q11.2 microdeletion
What are the features of DiGeorge Syndrome?
Small mouth Prominent nose Congenital heart defects Abnormal facies Thymic aplasia Cleft palate Hypocalcaemia/Hypoparathyroidism
What causes William’s Syndrome?
7q11.23 microdeletion (about 26 genes from long arm of chromosome 7)
What are the features of William’s syndrome?
Bright eyes Stellate irises Wide mouth Upturned nose Long philtrum Flattened nasal bridge Heart defects Inappropriately sociable
What causes Prader-Willi syndrome?
15q13 microdeletion
What are the features of Prader-Willi syndrome?
Hypotonia and abnormal neurological function
Hypogonadism
Developmental and cognitive delays
Hyperphagia
Obesity
Short stature
Behavioural and psychiatric disturbances
Constant, extreme, ravenous insatiable appetite
Marked skill in completing jigsaw puzzles
What causes Cat eye syndrome?
22 inverted duplication 22q11
What are the features of Cat eye syndrome?
Iris coloboma Anal atresia Ear tags and/or ear pits Heart defects Kidney malformations Marked variability
What is a pedigree?
Short hand to record a family tree
Why is diagnostic testing?
Part of clinical management. Confirm/refute clinical diagnosis. Assess carrier status
Who is diagnostic testing for?
Test an individual with a family history of the illness or other clinical indication. If early diagnosis reduces morbidity or mortality.
What is a karyotype?
Represents the cytogenetic characteristics of the individual - stained with giemsa for G banding
Which specimen contain spontaneously proliferating cells?
Bone marrow
Lymph nodes
Solid tumours
Chorionic villi (CVS)
Which specimens are routinely cultured in the laboratory?
Blood lymphocytes
Tissue biopsies (fibroblasts from skin etc)
Amniotic fluid samples
Long term CVS
