Genetics - Genetic Disorders Flashcards
What is Down’s syndrome?
It is a genetic disorder caused by the presence a copy of chromosome 21 (trisomy 21)
What are the three main mechanisms of Down’s syndrome?
Maternal nondisjunction
Robertsonian translation
Mocaicism
What is the most common mechanism of Down’s syndrome?
Maternal nondisjunction
What are the eight clinical features of Down’s syndrome?
Facial abnormalities
Flat occiput
Single palmar crease
Pronounced sandal gap
Hypotonia
Congenital heart defects
Duodenal artersia
Hirschprung’s disease
What six facial abnormalities are associated with Down’s?
Upslanting palpebral fissures
Epicanthic folds
Brushfield spots in iris
Protruding tongue
Small low-set ears
Round/flat face
What five cardiac abnormalities are associated with Down’s syndrome?
Endocardial cushion defect
Ventricular septal defect
Secundum atrial septal defect
Tetralogy of Fallot
Isolated patent ductus arteriosus
What is the most common cardiac abnormalities in Down’s syndrome?
Endocardial cushion defect
What are the eight later complications of Down’s syndrome?
Subfertility
Learning difficulties
Short stature
Respiratory infections
ALL
Hypothyroidism
Alzheimer’s disease
Atlantoaxial instability
What is the first line investigation used to screen for Down’s syndrome?
Combined test
What is the combined test?
Nuchal translucency measurement
Serum B-hCG levels
Pregnancy associated plasma protein A (PAPP-A)
When is the combined test conducted?
11 - 13+6 weeks
What combined test result indicates Down’s syndrome?
Thickened nuchal translucency
Increased b-hCG
Decreased PAPPA
What two other tests are used to screen for Down’s syndrome between 15-20 weeks?
Triple test
Quadruple test
What is the triple test?
Alpha-fetoprotein
Unconjugated estriol
b-hCG
What is the quadruple test?
Alpha-fetoprotein
Unconjugated estriol
b-hCG
Inhibin A
What is Patau’s syndrome?
It is a genetic disorder caused by the presence a copy of chromosome 13 (trisomy 13)
What are the five clinical features of Patau syndrome?
Microcephalic
Small eyes
Cleft lip/palate
Polydactyly
Scalp lesions
What is Edward’s syndrome?
It is a genetic disorder caused by the presence a copy of chromosome 18 (trisomy 18)
What are the four clinical features of Edward’s syndrome?
Micrognathia
Low-set ears
Rocker bottom feet
Overlapping of fingers
What is Turner’s syndrome?
It is caused by either the presence of only one sex chromosome (X) or a deletion of the short arm of one of the X chromosomes
What phenotype denotes Turner’s syndrome?
45,XO
OR
45,X
What is the most common mechanism of Turner’s syndrome?
Mosaicism
What is mosaicism?
It is defined as the presence of two genetically different populations of cells in the body
What are the twelve clinical features of Turner’s syndrome?
Short stature
Widely spaced nipples
Webbed neck
Cardiac abnormalities
Primary amenorrhoea
Cystic hygroma
High arched palate
Short forth metacarpal
Multiple pigmented naevei
Lymphoedmea
Hypothyroidism
Renal abnormalities
What two cardiac abnormalities are associated with Turner’s syndrome?
Bicuspid aortic valve
Coarctation of the aorta
What renal abnormality is associated with Turner’s syndrome?
Horshoe kidney
What is Klinfelter’s syndrome?
It is a genetic condition that results when a boy is born with an extra copy of the X chromosome
What phenotype denotes Klinfelter’s syndrome?
47, XXY
What are the five clinical features associated with Klinfelter’s syndrome?
Tall
Lack of secondary sexual characteristics
Small, firm testes
Infertile
Gynaecomastia
What genetic test is used to diagnose Klinefelter’s syndrome?
Karyotype
What blood test is used to indicate Klinefelter’s syndrome?
Increased gonadotropin levels
Low testosterone levels
What is Noonan’s syndrome?
It is a genetic condition associated with a PTPN11 mutation on chromosome 12
What inheritance is demonstrated in Noonan’s syndrome?
Autosomal dominant
What are the four clinical features of Noonan’s syndrome?
Webbed neck
Pectus excavatum
Short stature
Pulmonary stenosis
What is William’s syndrome?
It is an inherited neurodevelopmental disorder caused by a microdeletion on chromosome 7
What are the six clinical features of William’s syndrome?
Ellfin-like facies
Friendly character
Learning difficulties
Short stature
Transient neonatal hypercalcaemia
Supravalvular aortic stenosis
How do we diagnose William’s syndrome?
FISH study
What is DiGeorge syndrome?
It is a primary T-cell immunodeficiency disorder
What is the cause of DiGeorge syndrome?
A deletion of a section of chromosome 22
What are two other names for DiGeorge syndrome?
Velocardiofacial syndrome
22q11.2 deletion syndrome
What is the inheritance of DiGeorge syndrome?
Autosomal dominant
What are the six clinical features of DiGeorge syndrome?
CATCH
Cardiac abnormalities
Abnormal facies
Thymic aplasia
Cleft palate
Hypocalcaemia/ hypoparathyroidism
What is Marfan’s syndrome?
It is a genetic connective tissue disorder
It is caused by a defect in the FBN1 gene on chromosome 15 that codes for the protein fibrillin-1
What inheritance is demonstrated in Marfan’s syndrome?
Autosomal dominant
What are the ten clinical features of Marfan’s syndrome?
Tall stature
High-arched palate
Arachnodactyly
Pectus excavatum
Pes planus
Scoliosis
Cardiac abnormalities
Pneumothoraces
Eye abnormalities
Dural ectasia
What four cardiac abnormalities are associated with Marfan’s syndrome?
Dilation of the aortic sinuses
Aortic dissection
Aortic regurgitation
Mitral valve prolapse
What are the three eye abnormalities associated with Marfan’s syndrome?
Upwards lens dislocation
Blue sclera
Myopia
What is dural ectasia?
It is ballooning of the dural sac at the lumbosacral level
What scan do we conduct annually in Marfan’s syndrome patients?
ECHO scan
What two drugs are used to manage Marfan’s syndrome?
Beta-blockers
ARBs
What is phenylketonuria (PKU)?
It is a genetic condition caused by a disorder of phenylalanine metabolism
This is usually due to defect in phenylalanine hydroxylase, an enzyme which converts phenylalanine to tyrosine
This leads to an accumulation of phenylalanine
What type of inheritance is PKU?
Autosomal recessive
On what chromosome is phenylalanine hydroxylase located on?
12
When does PKU tend to present?
6 months
What are the five clinical features of PKU?
Developmental delay
Seizures
Learning disabilities
Eczema
Musty odour to urine and sweat
What test is used to diagnose PKU?
Guthrie test, also known as the heel prick test
When is the Guthrie test conducted?
5-9 days after birth
What blood result indicates PKU?
Hyperphenylalaninaemia
What urine result indicates PKU?
Phenylpyruvic acid
How do we manage PKU?
We advise dietary restrictions during pregnancy and after birth
What is pleiotropy? Name an example
It refers to a mutation in a single gene causing pathology in multiple organ systems
PKU
What is Prader Willi syndrome?
It is a genetic condition associated with the absence of the active Prader-Willi gene on the long arm of chromosome 15
What are the two pathophysiological causes of Prader Willi syndrome?
Microdeletion of paternal 15q11-13
Maternal uniparental disomy of chromosome 15
Prader Willi syndrome is an example of genetic imprinting. What does this mean?
It is defined as a difference in phenotype dependent on whether the mutation is maternal or paternal origin
What syndrome results in cases where the deletion of the Prader Willi gene is from the mother?
Angelman syndrome
What are the six clinical features of Prader Willi syndrome?
Hypotonia
Short stature
Hypogonadism
Learning difficulties
Childhood obesity
Behavioural problems
What is long QT syndrome?
It is an inherited condition associated with delayed repolarisation of the ventricles
What is the normal QT interval in males?
< 430ms
What is the normal QT interval in females?
< 450ms
What is the cause of long QT syndrome?
It caused by defects in the alpha subunit of the slow delayed rectifier potassium channel
What are the two congenital syndromes that cause long QT syndrome?
Romano-Ward syndrome
Jervell-Lange-Nielsen syndrome
What are the three classifications of long QT syndrome?
Long QT1
Long QT2
Long QT3
What is long QT1?
It is usually associated with exertional syncope, often swimming
What is long QT2?
It is usually associated with syncope occurring following emotional stress, exercise or auditory stimuli
What is long QT3?
It is usually associated with syncope at night or at rest
What scan is used to diagnose long QT syndrome?
ECG
What are the three features of long QT syndrome on an ECG scan?
Prolonged QT interval
Repolarisation anomalies
Paroxysmal polymorphic VT
How do we manage long QT syndrome?
Beta blockers
What are the two complications of long QT syndrome?
Ventricular tachycardia
Torsade de pointes
What is neurofibromatosis?
It is a genetic condition that that results in tumour growth along nerves
What is the inheritance of neurofibromatosis?
Autosomal dominant
What are the two classification of neurofibromatosis?
NF 1
NF 2
What is another term for NF1?
von Recklinghausen’s syndrome
What is the cause of NF1?
It is caused by a gene mutation on chromosome 17 which encodes neurofibromin
What are the six clinical features of NF1?
Café-au-lait spots
Axillary/groin freckles
Peripheral neurofibromas
Iris hamatomas
Scoliosis
Pheochromocytomas
What is the cause of NF2?
It is caused by gene mutation on chromosome 22
What are the four clinical features of NF2?
Bilateral vestibular schwannomas
Multiple intracranial schwannomas
Multiple intracranial mengiomas
Multiple intracranial ependymomas
What is tuberous sclerosis (TS)?
It is a genetic condition that causes benign tumours to develop in various areas of the body
What is the inheritance of tuberous sclerosis?
Autosomal dominant
What are the five cutaneous clinical features of tuberous sclerosis?
Depigmented ‘ash-leaf’ spots which fluoresce under UV light
Roughened patches of skin over lumbar spine
Angiofibromas
Subungual fibromata
Cafe-au-lait spots
What are the three neurological clinical features of tuberous sclerosis?
Developmental delay
Epilepsy
Intellectual impairment
