Genetics Flashcards
Name 5 autosomal recessive disease
Cystic fibrosis CAH (21 hydroxylase deficiency) Thalassemia Sickle cell anaemia Wilson disease
Name 6 autosomal dominant diseases
ADPKD Huntington’s Neurofibromatosis BRCA gene breast ca Von Willebrand Hereditary spherocytosis
Name 3 x linked recessive diseases
Duchenne
Haemophilia
G6PD
What does autosomal recessive mean
If BOTH parents arriers
25% child affected
50% to be carrier
Def of autosomal dominant
If 1 parent affected -
= 50% chance child to be affected
25% chance grandchild to be affected
Def of x linked recessive
If mother is carrier
50% chance male child is affected
If father affected
0% chance male child affected
100% chance of female carrier
Features of cystic fibrosis
AR mutation in CFTR gene
= cystic fibrosis transmembrane conductance regulator gene
== increased viscosity and thickness of body secretions
Salty skin, finer clubbing
Recurrent reproductive cough - sputum , chest infections
Long term - thick secretions block pancreatic duct - decreased protein and fat absorption - failure to thrive + fat containing stool (steatorrhoea)-DM1 from pancreatic damage
CF in males usually associated with
Congenital absence of Vas Deferens = infertility
Complication of CF early after birth
Meconium ileus
- meconium might no pass due to thickness
Long term complications of Cystic fibrosis
Diabetes
Cirrhosis
Respiratory failure
Bronchiectasis
Dx of cystic fibrosis + neonatal screening
NS - Guthrie test
- heel prick when baby is 7-10 days old
If +ve - confirm by sweat test and genetic testing for CFTR gene
If not dx as neonate
Sweat test , genetic testing for CFTR
Treatment of cystic fibrosis
No cure , ease symptoms
Azithromycin - long term lung infections
Inhaled hypertonic saline/ salbutamol
Lung transplant
Pancreatic enzyme replacement + fat soluble vitamins
Chest physio - short term benefits
Life expectancy in CF
42-50 YO
80% death due to lung problems
Common in Northern European ancestry
Chance of children to be affected in Cystic fibrosis
CF - autosomal recessive
Children -
25% affected
50% carriers
Important association of polycystic kidney disease
Cerebral aneurysm
- if ruptures can cause SAH
Chance of child to be affected with Polycystic kidney disease if 1 parent has the disease
50%
Features of ADPKD
Abdominal/flank/back pain
Hematuria
HTN - common early manifestation
Assoc with cerebral aneurysm
Blood pressure control in ADPKD
ACEi or ARBs
45 XO =
Turners syndrome
Female
Features of turners syndrome
Learning difficulties Infertility - ovarian dysgenesis / ovarian failure - 1ry amennorrhoea Short stature Short webbed neck Widely spaced nipples Impaired pubertal growth Bicuspid aortic valve.
What is NOT a RF for Turner’s syndrome
Advanced maternal age
What is used during childhood of person with turner’s syndrome
Growth hormone -to increase height
Oestrogen replacement therapy - enhance breast and hip development ad prevent osteoporosis
Deletion of some paternal chromosome 15 genes
Prader Willi syndrome
Prader willi syndrome
Features
- neonatal
-childhood
Neo - floppy baby , almond shaped eyes, short extremities, thin upper lip and downturned mouth
Child - excessive eating (hyperphagia), obese and short, learning difficulties, self injurious behaviour, growth abnormality
Inheritance pattern of DMD
X linked recessive
Features of DMD incl age group
4-8Y , boy Starts walking late (>/=18 months ) normal is @ 12 mo Growers sign Proximal muscle weak was, waste Waddling gait , can’t run Raised CK , ALT AST \+- resp/cardiac manifestations
Initial test for DMD
CK - creatine kinase
Investigations for dx of DMD
CK
Muscle biopsy
Genetic testing = obligatory after +ve muscle biopsy
Where is the mutation defect in DMD
Striated muscle - dystrophin protein mutation defect
What is Patau syndrome
Features
Trisomy 13
Cleft lip and palate
Small head and eyes
Polydactyly
What is Edward syndrome
Features
Trisomy 18
Rocker bottom feet - prominent calcaneous
Small head and jaw
Hands clenched into fists w/ overriding fingers
Trisomy 21 features
= down’s Duodenal atresia Single palmar crease Space b/w 1st and 2nd toe Upward slanting eyes + depressed nasal bridge Abnormal ear shape Small mouth ; large tongue Joint laxity
Congenital adrenal hyperplasia
Inheritance pattern
Most common form
Autosomal recessive
21 hydroxylase deficiency
Features of CAH
Classic presentations
Cortisol deficiency +- aldosterone deficiency +- androgen excess
Ambiguous genitalia - in females
Hirsutism, early pubarche, oligomenorrhoea
Penile enlargement, hyperpigmentation - males
Salt wasting - infant males (aldosterone def)
Vomiting, wt loss, lethargy, dehydration, hypoNa, HypERkalemia
= 11 beta hydroxylase deficiency
Cause of hirsutism early pubarche and oligomenorrhoea
In CAH
17 hydroxyprogesterone
- converted into androgens, testosterone, androstenedione
Klinefelter syndrome
Features
47 XXY males
G FELTER
Gynecomastia Facial hair - low Estrogen high ;Low testosterone Long limbs Tall, slim Elevated FSH, LH Rage - aggressive behaviour
Hypogonadism = small testes - azospermia - male infertility
Best diagnosis of klinefelter
Karyotyping
= chromosomal analysis
47 XXY
Features of Marfans syndrome
Tall thin boy Spontaneous pneumothorax Long extremities Scoliosis Flexible joints Myopia
Absent thymic shadow seen in
DiGeorge syndrome
Huntington’s disease
Inheritance pattern
Early signs
Late signs
AD with anticipation
= sx appears earlier and earlier in next generations
Early - personality changes, self neglect, clumsiness
Progressive cognitive impairment
Later - chorea, dystocia, rigidity, dementia
Investigating potential genetic disease
- before pregnancy
Pre-implantation genetic diagnosis (PGD)
- fertilisation in vitro in the lab - embryos tested for genetic abnormalities
1 or 2 unaffected embryos implanted into uterus
Genetic investigation of week 11-14 of pregnancy
Chorionic villous sampling
- small placental sample tested
Week 15-20 of pregnancy - what test done for investigation of genetic
Amniocentesis
Diagnostic criteria for NF
- 6 or more cafe au lait macules
- >.5cm in children , >1.5cm in adults - 2 or more cutaneous/subcutaneous NF or 1 plexiform neurofibroma
- Axillary or groin freckling
- Optic pathway glioma
- 2 or more Lisch nodules (iris hamartoma on slit lamp)
- Bony dysplasia (sphenoid wing dysplasia, bowing of long bone +- pseudoarthrosis)
- 1st degree relative with NF1
NF1 vs NF2
NF1 - more skin lesions
= cafe au lait, axillary, groin freckles, scoliosis,
NF2 - more CNS tumours
- bilateral acoustic neuroma, multiple intracranial schwannoma, meningiomas
What should be done for a woman with strong family history (1st /2nd degree) of ovarian ca
(3)
Do pelvic US
If Unremarkable - genetic counselling for full risk assessment
If high risk - offer prophylactic saplings-oophorectomy
If there are manifestations of ovarian ca - US + CA 125 level
Inheritance pattern of Alport syndrome
X linked
Features of Alport syndrome
Kidney disease - hematuria, proteinuria —> (ESRD)
Hearing loss (SNHL)
Eye abnormalities
What is the chance of a grandchild is affected in AD?
25%
Strongest RF of Alzheimer’s
Alzheimer’s - Autosomal dominant
APOE e4 gene (APOE e4 allele)
Inheritance pattern of Becker’s muscular dystrophy
X linked recessive
Most appropriate approach to evaluate short stature (constiutional delay in growth and puberty)
Wrist Xray for bone age
BRCA1 gene mutation penetrance
Autosomal dominant with incomplete penetrance
- 80% will develop breast ca
NF1 - complete penetrance
A disease that is autosomal dominant with anticipation
Huntington’s
Fragile X syndrome inheritance pattern
X linked dominant
Mother
50% will have it - male or femal e
Father affected
100% females affected
