Genetics Flashcards
What is Turner’s syndrome?
When a female has a single X chromosome
What is the genotype of someone with Turner’s syndrome?
45XO
What are the classic features of Turner’s syndrome?
Short stature
Webbed neck
Widely spaced nipples
Cubitus valgus - where the forearm is angled away from the body when fully extended
Late or incomplete puberty
Infertility
What are the complications associated with Turner’s syndrome?
Recurrent otitis media
Recurrent UTIs
Congenital heart defects - coarctation of aortaand biscuspid aortic valve
Hypertension
Obesity
Diabetes
Infertility
What investigations would you perform for Turner’s syndrome?
Genetic karyotyping
What is the management of Turner’s syndrome?
Growth hormone for short stature
Oestrogen and progesterone to help establish secondary sexual characteristics
Fertility treatment
Regular monitoring and managment of complications
What is Klinefelter’s syndrome?
When a male has an additional X chromosome
What is the genotype of someone with Klinefelter syndrome?
47XXY
When does Klinefelter syndrome present?
Males typically appear normal until puberty
Puberty can also be delayed
What are the symptoms of Klinefelter syndrome?
Tall and slim
Gynaecomastia
Small testicles
Weaker muscles
Shyness
Reduced libido
What is the management of Klinefelter syndrome?
Testosterone injections
IVF techniques
Breast reduction surgery
Physiotherapy, speech and language therapy, occupational therapy
What is cystic fibrosis?
A genetic condition affecting mucous glands
What is the inheritance pattern of CF?
Autosomal recessive
What gene is affected in CF?
CFTR gene (cystic fibrosis transmembrane conductance regulatory gene)
What is the most common mutation of the CFTR gene?
delta-F508
Which chromsome is the CFTR gene on?
Chromosome 7
What impact does CF have on the respiratory system?
Thick respiratory secretions due to abnormal transport of chloride ions and sodium
What impact does CF have on the pancreas?
The pancreatic duct is usually congenitally occluded resulting in pancreatic insufficiency
What impact does CF have on the GI system?
The small intestine secretes viscous mucus that can cause bowel obstruction in-utero, resulting in meconium ileus. The secretions can also cause cholestasis and neonatal jaundice
What impact does CF have on the reproductive tract?
98% of men with CF are infertile due to a congenital absence of the vas deferens
How many people are carriers of a CF mutation?
1 in 25
How does CF present in neonates?
Meconium ileus
Prolonged neonatal jaundice
Failure to thrive
How does CF present in infancy?
Failure to thrive
Recurrent infections
Pancreatic insufficiency - steatorrhoea
How does CF present in childhood?
Nasal polyps
Rectal prolapse
Sinusitis
How does CF present in adolescence?
Pancreatic insufficiency - diabetes
Chronic lung disease
Liver cirrhosis
Gallstones
What is the gold standard investigation for CF?
Sweat test
What results are seen in a positive sweat test?
High chloride level
What test can be done in neonates to diagnose CF?
Newborn heelprick test
What conditions are screened for in the newborn heelprick test?
Cystic fibrosis
Sickle cell anaemia
Congenital hypothyroidism
6 different metabolic conditions
Which bacteria commonly colonise people with CF?
Staphylococcus aureus
Pseudomonas aeruginosa
What other investigations can be performed to help monitor CF?
LFTs
CXR
Cough swab/sputum sample
Glucose tolerance test
Bone profile
Spirometry
What are the management options for CF?
Patient and family education
Chest clearance and physiotherapy
Exercise
High calorie diet
CREON tablets for pancreatic insufficiency
Antibiotics for chest infections
Bronchodilators
Prophylactic flucloxacillin
What is Patau’s syndrome?
Trisomy 13
What is Edward’s syndrome?
Trisomy 18
What is the management of Turner Syndrome?
Growth hormone
Oestrogen and progesterone to establish secondary female sexual characterstics
Fertility treatment
What are the associations of Klinefelter’s?
Diabetes
Anxiety
Increased risk of breast cancer
Osteoporosis
What is noonan syndrome?
A genetic disorder with a wide range of features across the body
What is the inheritance pattern of noonan syndrome?
Autosomal dominant
What is the presentation of noonan syndrome?
Short stature
Broad forehead
Wide space between eyes - hypertelorism
Downward sloping eyes with ptosis
Prominent nasolabial folds
What conditions are associated with noonan syndrome?
Congenital heart disease - pulmonary valve stenosis, hypertrophic cardiomyopathy, ASD
Undescended testes
Learning disability
Bleeding disorders
Lymphodema
Increased risk of leukaemia and neuroblastoma
What is the management of noonan syndrome?
Supportive
Surgery for congenital heart disease
What is fragile X syndrome?
A genetic condition that causes a range of developmental problems
What is the inheritance pattern of fragile X syndrome?
X linked (unclear if dominant or recessive)
What is the presentation of fragile X syndrome?
Intellectual disability
Long, narrow face
Large ears
Large testicles post puberty
Social anxiety
ADHD and autisum
What mutation causes fragile X syndrome?
CGG trinucleotide repeat in the FMR1 gene
What is Prader Willi syndrome?
A genetic condition caused by loss of functionality of the proximal arm of chromsome 15
What are the modes of inheritance of Prader Willi syndrome?
Deletion of the proximal arm
Inheritance of two copies of from mother
What is the presentation of Prader Willi syndrome?
Constant insatiable hunger
Hypotonia as an infant
Learning disability
Developmental delay in early childhood
Mental health problems
Short stature
What is the definitive diagnosis for Prader-Willi syndrome?
Genetic testing
What is the management of Prader-Willi syndrome?
Growth hormone
Dieticians - management of overeating
Education support
PTOT
What is Angelman syndrome?
A genetic condition caused by a loss of function of the UBE3A gene
What is the mode of inheritance of Angelman syndrome?
Deletion on mother’s chromosome 15
Inheritance of two copies of gene from father
What is the presentation of Angelman syndrome?
Delayed development - especially speech development
Happy demeanour
Fascination with water
Ataxia
ADHD
Epilepsy
Dysmorphic features
Fair skin, light hair and blue eyes
Widely space teeth
What is the management of Angelman syndrome?
PTOT
Psychological support
Social services
Educational support
Anti-epileptics
What are the features of Patau’s syndrome?
Holoprosencephaly - failure of the two cerebral hemispheres to divide
Cleft lip and palate
Microcephaly
Polydactyly
Congenital heart disease
What are the features of Edwards syndrome?
Low set ears
Small jaw (micrognathia)
Overlapping 4th and 5th fingers
Rocked bottomed feet
Congenital heart disease
What is Williams syndrome?
A deletion on chromosome 7 that results in having only one copy of the genes from this region
How does Williams syndrome occur?
A random deletion around the time of conception
What are the features of Williams syndrome?
Broad forehead
Starburst eyes (star like pattern on the iris)
Flattened nasal bridge
Long philtrum
Wide mouth and widely spaced teeth
Mild learning disability
Socialable and trusting personality
What conditions are associated with Williams syndrome?
Supravalvular aortic stenosis
ADHD
Hypertension
Hypercalcaemia
What is the management of Williams sydrome?
MDT approach
Low calcium diet
Echocardiograms and BP monitoring (for hypertension and stenosis)
What is Kallmann’s syndrome?
An X-linked recessive condition that delays puberty due to hypogonadotrophic hypogonadism
Why does Kallman’s syndrome cause delayed puberty?
It is thought to be due to a failure of GnRH secreting neurons migrating to the hypothalamus
What is the presentation of Kallman syndrome?
Anosmia
Delayed puberty
Hypogonadism
Normal or above average height
What hormone levels are seen in Kallman syndrome?
Low testosterone levels
LH and FSH levels low
What medications can specifically be used to treat the most common CF mutation?
Lumacaftor/ivacaftor
What are the functions of lumacaftor and ivacaftor?
Lumacaftor helps the CFTR protein form and move to the surface
Ivacaftor helps the CFTR protein to stay open for longer
