Paediatric - Genetics Flashcards
How many chromosomes are there in the human body?
46 (22 pairs + 2 sex chromosomes)
What are males and females sex chromosomes?
- Male = XY
- Female = XX
What are the other 44 chromosomes called?
Autosomes
What is genotype vs phenotype?
- Genotype = actual genes we have
- Phenotype = how we express those genes in characteristics
What is an intron vs exon in DNA?
- Intron = non-coding portion of DNA
- Exon = coding portion of DNA
What is the process of creating a gamete known as?
Meiosis
Where does the child inherit the mitochondria from?
The mother!!!
What are the effects when there is a mitochondrial disease (2)?
- Poor production of ATP –> myopathy (abnormal muscle function)
- Can also cause deafness, blindness, epilepsy and diabetes
What is kleinfelters syndrome?
When a male has an extra X chromosome
When do features of kleinfelters usually display?
At puberty
What are the features of kleinfelters (9)?
- Tall
- Wide hips
- Gynaecomastia
- Weaker
- Small testicles
- Reduced libido
- Shyness
- Infertility
- Mild learning difficulties
basically all things feminine
How is kleinfelters managed (4)?
- Testosterone
- IVF
- Breast reduction
- MDT (physio, educational support, etc…)
What conditions is there a slight increased risk of for those with kleinfelters (4)?
- Breast cancer
- Osteoporosis
- Diabetes
- Anxiety/ depression
What is turners syndrome?
A female who has a single X chromosome
When does turners syndrome usually present?
Pubity
What are the 4 key features of Turners syndrome?
- Short
- Webbed neck
- Wide nipples + wide chest
- Primary amenorrhoea
What are the other features of turners syndrome (other than short, amenorrhoea, webbed neck and wide nipples) (5)?
- High arch palate
- Downward sloping eyes (-ve canthal tilt/ prey eyes) with ptosis
- Cubitus valgus
- Underdeveloped ovaries + infertility
- Late puberty
What is cubitus valgus?
When elbows are extended they are angled away from the body
turners
What heart defects are associated with turners (2)?
- Bicuspid aortic valve = MC
-
Coarcation of the aorta
dissection of aorta is most serious long term health risk
What genitourinary defect is associated with turners?
Horseshoe kidney
What features upon investigation would suggest turners syndrome (2)?
- Raised FSH/LH
- Oedema in hands/ feet (antenatal USS)
What are the 3 most common forms of trisomy?
- Downs
- Edwards
- Pataus
What trisomy is downs syndrome?
21
What trisomy is Edward’s syndrome?
18
W-E = 18
What trisomy is Patau’s
13
p(16) + t(20) - a(1) - a(1) - u(21) = 13
What are the features of downs syndrome (6)?
- Upslanting palpebral fissures
- Epicanthic folds
- Small low set ears
- Single palmar crease
- Hypotonia
- Short stature
What 3 conditions are children with downs syndrome commonly born with?
- Duodenal atresia
- Hirschprungs disease
- CHD
What heart defects are common in those with downs syndrome (3)?
- AVSD (endocardial cushion defect) = MC
- ASD/ VSD
- Tetralogy of fallot
What are 5 long term complications of downs syndrome?
- Alzheimers
- ALL
- Infertility
- Hypothyroid
- Eustachian tube abnormalities + repeated U/LRTI
Who/ what is involved in the management of those with downs syndrome (8)?
- Occupational health
- SALT
- Physio
- Dietician
- Paediatrician
- GP
- Opticians
- Educational support plans
What are some routine follow ups for children with downs syndrome (4)?
- 2 yearly thyroid checks
- Echo (for heart defects)
- Audiometry
- Eye checks
What is the life expectancy of those with downs?
60 years
How common is down syndrome?
1 in 1000
What is the prognosis/life expectancy for Edwards syndrome?
Most don’t live past 1 year and die in first few weeks
What are the features of Edwards syndrome (4)?
- Micrognathia (small lower jaw)
- Low-set ears
- Rocker bottom feet
- Overlapping fingers
What conditions are associated with Edwards syndrome (3)?
- Congenital heart defects
- Kidney malformation
- GI anomalies
How is Edwards syndrome managed?
Mostly supportive, palliative care once born
How common is Edward’s syndrome?
1 in 5000 births
What is the prognosis/ life expectancy of Patau’s syndrome?
Very poor, most die in first few weeks
What are the features of pataus syndrome (4)?
- Cleft lip
- Microcephaly, small eyes
- Polydactyly
- Rocker bottom feet
What are some complications of Patau’s (2)?
- Severe congenital heart defects
- Brain/ spinal cord malformations
How is pataus managed?
Supportive/ palliative care
How common is pataus syndrome?
1 in 15000
What is the inheritance of fragile X syndrome?
X-linked dominant genetic condition that affects males more
What gene is affected in fragile X syndrome?
FMR1 (fragile X mental retardation) gene
What are the features of fragile X syndrome (5)?
- Learning difficulties
- Macrocephaly
- Long face
- Large ears
- Macro-orchidism (large testes)
How is fragile X managed?
MDT!!!
What is angelman syndrome (chromosome and gene affected)?
Loss of function of the UBE3A gene on chromosome 15 inherited from the mother - 15q11-13
Why is angelman syndrome caused by a defect in the mothers UBE3A gene not the fathers?
In the developing foetus the fathers UBE3A genes in the brain are inactivated
What two situations in terms of inheritance can lead to angelman syndrome?
- Deletion/ mutation in UBE3A genes on the mothers chromosome 15
- Two male versions of chromosome 15 inherited and no copy from mother
What are the features of angelman syndrome (8)?
- Delayed development + learning difficulty
- Severe delay/ absence of speech
- Ataxia
- Unusually happy
- Microcephaly
- Seizures
- Wide mouth, spaced teeth
- Fascination with water
What is prader willi syndrome (chromosome and gene affected)?
Loss of function of the proximal arm of chromosome 15 inherited from the father - 15q-11-13
What two situations in terms of inheritance can lead to prader willi syndrome?
- Inheritance of two maternal chromosome 15
- Deletion of a portion of paternal chromosome 15
What are the features of prader willi syndrome (4)?
- Constant hunger –> obesity
- Hypotonia
- Learning disability
- Narrow forehead
How is prader willi managed?
- Limit food intake
- Growth hormone - improve muscle development
How is Noonan syndrome inherited?
Autosomal dominant
What are the features of Noonan syndrome (5)?
- Webbed neck
- Wide nipples
- Short stature
- Pectus excavatum
- Low set ears
What conditions are associated with noonans (2)?
- Pulomary stenosis
- Bleeding disorders (factor XI deficiency)
What is williams syndrome?
A deletion on long arm of chromosome 7 resulting in only 1 copy of the deleted genes being present (7q11-23)
What are the features of Williams syndrome (5)?
- Wide mouth, wide spaced teeth
- Elfin facies
- Learning disability
- Very friendly/ sociable
- Starburst eyes
What conditions are associated with Williams (2)?
- Supravalvular aortic stenosis (narrowing above valve)
- Hypercalcaemia
What are the 3 features of Pierre robin disorder?
- Micrognathia
- Glossoptosis (causing posterior displacement of the tongue)
- Cleft pallate
What is cystic fibrosis?
Autosomal recessive genetic condition affecting mucous glands
What gene and chromosome are affected by CF?
CFTR (cystic fibrosis transmembrane conductance regulator) gene on chromosome 7
What is the umbrella term for genetic conditions that cause gradual weakening and waisting of muscles?
Muscular dystrophy
What is the most common form of muscular dystrophy?
Duchennes muscular dystrophy
How is Duchennes muscular dystrophy inherited and the genetic defect?
X-linked recessive (Xp21 deletion or mutation)
mutation is beckers muscular dystrophy
What is the mechanism by which DMD causes muscle waisting/ weakening?
The gene coding for dystrophin is defective. Dystrophin is a protein which holds muscles together at a cellular level.
When does DMD usually present?
3-5 years
What are the signs/ symptoms of DMD (4)?
- Weakness
- Loss of muscle mass
- Skeletal deformities
- Difficulty getting up
What is a sign of DMD seen when children are trying to stand?
Gower’s sign
*because they can’t go anywhere**
What is Gower’s sign?
Standing by walking hands up legs
What is an example of a chromosomal deletion disorder and what chromosome is affected?
Cri du chat (deleted portion of chromosome 5)
‘cry like a cat’ because the child has a cat like cry as an infant
What is an example of a duplication chromosomal disorder?
Charcot marie tooth (duplicated short arm of chromosome 17)
What is an example of a translocation chromosome disorder?
Philadelphia chromosome translocation (between 9 and 22)
risk factor for the development of AML
What is a robertsonian translocation?
When two long arms of chromosomes join together and the short arms are lost (resulting in the effective loss of 1 chromosome)
What is mosaicism?
When the chromosomal abnormality happens after conception so a portion of the cells are normal and a portion have abnormal genetic material
How is marfans syndrome often inherited?
Autosomal dominant
When should the offspring of those with genetic disorders be offered testing for the disorder?
- If affects management under 18 than offer in childhood
- If does not affect management, then offer testing once in adulthood and can make an informed decision
What is the defect seen in DiGeorge syndrome?
22q11.2
What are the features of digeorge syndrome (5)?
- CV Abnormality
- Thymic hypoplasia/ absence
- Cleft palate
- Hypocalcaemia
- Chromosome 22 affected
CATCH-22
