1
Q
Remind yourself of what a deletion chromosome disorder is
State an example
A
- Portion of chromosome missing
- Cri du chat (missing portion of chromosome 5)
2
Q
Remind yourself what a duplication chromosome disorder is
State an example
A
- Portion of chromosome is duplicated
- Charcot-Marie-Tooth (short arm of chromosome 17)
3
Q
State and briefly describe three types of translocation
A
- Reciprocal translocation: portion of one chromosome is swapped for another; occurs between two homologous chromosomes
- Non-reciprocal translocation: portion of one chromosome leaves first chromosome and attaches to another without any exchange taking place; occurs between two homologous chromosomes
- Robertsonian translocation: occurs in acrocentric chromosomes 13, 14, 15, 21 & 22 (these have a long arm which has most of genetic info and a short arm containing little genetic info). Lose short arm completely and the two long arms connect at centromere. Lose a chromosome. Phenotypically normal but have 45 chromosomes leading to problems in offspring
4
Q
Remind yourself what a trisomy chromosome disorder is
State some examples
A
- Person has three copies of a particular chromosome
- Examples:
- Down’s syndrome: trisomy 21
- Edwards syndrome: trisomy 18
- Patau syndrome: trisomy 13
5
Q
Remind yourself what mosaicism is
A
cells of the body have different numbers or arrangements of chromosomes. For example, if an individual has mosaic trisomy 18, this means that some of the cells have three copies of chromosome 18 while other cells have two copies of chromosome 18.
Mutation occurs after conception.
6
Q
Mitochondrial disorders are common; true or false?
A
False; rare
7
Q
State some examples of problems mitochondrial disorders can cause
A
- Myopathies (due to poor production of ATP)
- Rare forms of:
- Deafness
- Blindness
- Diabetes mellitus
- Epilepsy
8
Q
Where is DNA in mitochondria stored?
How is the DNA in mitochondria arranged?
A
- Mitochondria have own DNA separate from cell nucleus; found in matrix of mitochondria
- Arranged in a circle
9
Q
Mitochondrial disorders are caused by maternal inheritance; explain how mitochondrial disorders show maternal inheritance
A
- At conception, sperm enters egg and DNA of both nuclei combine
- Mitochondria in sperm is found in the tail which doesn’t enter the egg
- Hence, father doesn’t contribute to any mitochondria in zygote (and hence the fetus and child)
- Mitochondrial DNA is from mother
- However, must consider that not all mitochondria in mother’s cells will be affected; the proportion of affected mitochondria that are passed on to offspring will determine whether individual is affected
10
Q
What is diagnostic genetic testing?
State an example
A
- Testing fetus or person for a suspected genetic condition
- E.g. Down’s syndrome, Turner syndrome
11
Q
What is predictive testing?
State an example
A
- Testing a person for a specific mutation that has implications for them in the future
- E.g. BRCA1 breast cancer gene
12
Q
What is carrier testing?
State an example
A
- Testing patient or potential/future parents for the gene for a specific autosomal recessive condition to calculate risk of passing it to their children
- E.g. cystic fibrosis
13
Q
Karyotyping, microarray testing, specific gene testing & DNA sequencing are examples of genetic tests we can do. Describe karyotyping
A
- Need mitotically dividing cells as obtain chromosomes from metaphase spread
- Look at number, size and structure of chromosomes
- Helpful in e.g. Down’s syndrome, Turner syndrome
14
Q
Karyotyping, microarray testing, specific gene testing & DNA sequencing are examples of genetic tests we can do. Describe microarray testing
A
Cut up genetic material from individual using enzymes. Different genes have different molecular weights. Apply cut up genetic material to a plate that separates molecule of different weights into different locations allowing you to see what genes person expresses.
For example, if you know that the gene for cystic fibrosis is a certain size, and when this gene is chopped out and applied to the plate it ends up in a specific location on the plate, you can test an individual to see whether they have a clump of molecules at that location. If they do, this suggests they are expressing that gene.
15
Q
Karyotyping, microarray testing, specific gene testing & DNA sequencing are examples of genetic tests we can do. Describe specific gene testing
A
Split two strands of DNA. Add a gene probe (single strand of DNA that is complementary to the specific gene you want to test for). When mix DNA with gene probe if gene probe bonds with DNA then you know that particular gene is present.
16
Q
Karyotyping, microarray testing, specific gene testing & DNA sequencing are examples of genetic tests we can do. Describe DNA sequencing
A
- Only used for research purposes; no role in clinical practice
- Split two strands of DNA and watch as individual nucleotides are added to a single strand of DNA to reveal exact sequence of nucleotides in DNA
17
Q
What karyotype do people with Klinefelter syndrome have?
A
Additional X chromosome(s)
Could be 47XXY, 48XXXY, 49XXXXY….
18
Q
State some clinical features of Klinefelter syndrome
A
Note: additional X chromosomes associated with more severe features. Children often appear normal until puberty when may develop:
- Taller height
- Wider hips
- Gynaecomastia
- Weaker muscles
- Lack of secondary sexual characteristics
- Small, firm testicles
- Reduced libido
- Infertility
- Subtle learning difficulties (particularly affecting speech & language)
19
Q
Discuss the management of Klinefelter syndrome
A
No cure, treatment centred around helping with features. Involves MDT:
- Testosterone injections
- Advanced IVF techniques to improve fertility
- Breast reduction surgery
- SALT input
- Occupational therapy
- Physiotherapy (strengthen muscles)
- Educational support (for learning disabilities)
20
Q
Discuss the prognosis of Klinefelter syndrome
A
- Nearly normal life expectancy
- Slight increased risk of:
- Breast ca compared to other males (
- Osteoporosis
- Diabetes
- Anxiety
- Depression
- Infertility can occasionally be treated with advanced IVF techniques
21
Q
What would:
- GNRH
- Testosterone
…levels be in Klinefelter syndrome?
A
- GNRH: high
- Testosterone: low
22
Q
What is the karyotype for Turner’s syndrome?
A
- 45XO (only one X chromosome or deletion of the short arm of one of X chromosomes)
23
Q
State some clinical features of Turner’s syndrome
A
- Short stature
- Webbed neck
- High arching palate
- Downward sloping eyes with ptosis
- Broad/shield-like chest with widely spaced nipples
- Cubitus valgus
- Short 4th metacarpal
- Underdeveloped ovaries with reduced function
- Late or incomplete puberty
- Most women are infertile
24
Q
There are many conditions associated with Turner’s syndrome; state some
A
- Recurrent otitis media
- Recurrent urinary tract infections
- Coarctation of the aorta
- Bicuspid aortic valve
- Hypothyroidism
- Hypertension
- Obesity
- Diabetes
- Osteoporosis
- Crohn’s disease
- Various specific learning disabilities
- Cystic hygroma (often diagnosed prenatally)
- Horse-shoe kidney
- Lymphoedema in neonates (especially feet)
25
Discuss the management of Turner's syndrome
Treatment centred around helping symptoms and features of condition:
* Growth hormone injections *(improve short stature)*
* Oestrogen & progesterone replacement *(help development of secondary female sexual characteristics)*
* Fertility treatment *(increase chances)*
* Monitoring for associated conditions (e.g. hypertension, diabetes, hypothyroidism, osteoporosis etc…)
26
Discuss the management of Turner's syndrome
Treatment centred around helping symptoms and features of condition:
* Growth hormone injections *(improve short stature)*
* Oestrogen & progesterone replacement *(help development of secondary female sexual characteristics)*
* Fertility treatment *(increase chances)*
* Monitoring for associated conditions (e.g. hypertension, diabetes, hypothyroidism, osteoporosis etc…)
27
Discuss the prognosis of Turner's syndrome
Life expectancy close to normal
Most women infertile (fertility treatments can help)
28
What genetic mutation occurs in Noonan's syndrome?
State the inheritance pattern of Noonan's syndrome
* Number of different genes that cause Noonan's
* Majority is **autosomal dominant**
29
State some features of Noonan's syndrome
* Short stature
* Broad forehead
* Downward sloping eyes with ptosis
* Short stature
* Broad forehead & triangular shaped head
* Downward sloping eyes with ptosis
* Hypertelorism (wide space between the eyes)
* Prominent nasolabial folds
* Low set ears
* Webbed neck
* Widely spaced nipples (wide space between the eyes)
* Prominent nasolabial folds
* Low set ears
* Webbed neck
* Widely spaced nipples
30
There are many conditions associated with Noonan's syndrome; state some
* Congenital heart disease e.g.
* pulmonary valve stenosis
* ASD
* Hypertrophic cardiomyopathy
* Cryptorchidism
* Learning disability
* Bleeding disorders (factor XI deficiency)
* Lymphoedema
* Increased risk of leukaemia and neuroblastoma
31
Discuss the management of Noonan's syndrome
No cure, management is centred around supporting with features of condition and complications via MDT. Main complication is congenital heart disease which will require corrective surgery.
32
What is the inheritance pattern for Marfan's syndrome?
What mutation is present?
* Autosomal dominant
* Defect in FBN1 gene on chromosome 15 that codes for the protein fibrillin 1
33
State some features of Marfan's syndrome
* Tall stature (arm span:height \>1.05)
* Long neck
* Long limbs
* Long fingers (arachnodactyly)
* High arch palate
* Downward sloping palpable fissures
* Blue sclera
* Hypermobility
* Pectus carinatum or pectus excavatum
* Pes planus
* Scoliosis of 20 degrees
34
Describe two ways you can test for arachnodactyly
* Ask them to cross thumb across palm; if tip of thumb goes past opposite edge of hand this indicates arachnodactyly
* Ask them to wrap thumb & fingers of one hand around other wrist; if thumb & fingers overlap indicates arachondactyly
35
There are numerous conditions associated with Marfan's syndrome; state some
* Mitral valve prolapse (with regurgitation)~ 75%
* Aortic valve prolapse (with regurgitation)
* Aortic root dilation and aneurysms
* Lens dislocation in the eye
* Joint dislocations and pain due to hypermobility
* Scoliosis of the spine
* Pneumothorax
* Gastro-oesophageal reflux
36
Discuss the management of Marfan's syndrome
Management is aimed at helping symptoms/features and preventing complications. Involves MDT:
* Treatment centred around reducing cardiac complications e.g. valve prolapse & aortic aneurysms is focused on **minimising BP and HR**:
* Lifestyle: avoid caffeine & other stimulants, intense exercise
* Beta blockers, angiotensin II receptor blockers
* **Counselling about pregnancy** (as have significant risk of aortic aneurysms)
* **Physiotherapy**: strengthen joints and reduce symptoms such as pain due to hypermobility
* **Genetic counselling**
* **Regular monitoring for complications:** yearly ECHOs, ophthalmology reviews
37
What is the life expectancy of Marfan's syndrome?
What is leading cause of death?
* ~70yrs (improved a lot in recent years)
* Leading cause of death is aortic dissection and other CV problems
38
What gene is affected in fragile X syndrome?
What is the inheritance pattern?
Who is affected; males or females?
* **Mutation in FMR1 (fragile X mental retardation 1) gene on the X chromosome. Trinucleotide repeat disorder.** *\*The gene codes for fragile X mental retardation protein which has a role in cognitive development in brain)*
* **X-linked** *(unclear if dominant or recessive)*
* **Males are always affected but females vary** in how much they are affected *(since they have two copies of gene)*
39
Describe clinical features of Fragile X syndrome
* Delay in speech and language
* Intellectual disability
* Long, narrow face
* High arched palate
* Large ears
* Large testicles after puberty
* Hypermobile joints (particularly in the hands)
* Hypotonia
* Attention deficit hyperactivity disorder (ADHD)
* Autism
* Seizures
* Mitral valve prolpase
40
Discuss the management of fragile X syndrome
Management is based around treating symptoms/features. Involves MDT to help manage e.g. autism, ADHD, learning disabilities, seizures etc…
41
Discuss the prognosis of fragile X syndrome
~normal life expectancy (dependent on associated disabilities & complications)
42
What genetic mutation occurs in Prader-Willi syndrome?
**Loss of functional genes on the** **proximal aspect of long arm of chromosome 15 inherited from the father.** Can be due to **deletion of this portion of gene (most common)** or due to **both copies of chromosome 15 being inherited from mother.** *One of genes affected/located in proximal aspect of chromosome 15 is the Prader-Willi gene.*
* \*\*Some genes on chromosome 15 are only active (or "expressed") on the copy that is* *inherited* *from a person's father (the paternal copy). When genes are only active if inherited from a specific parent, it is called* [*genomic imprinting*](http://ghr.nlm.nih.gov/handbook/inheritance/updimprinting)*.*
* \*\*If inherited from mother it is Angelman syndrome.*
43
State some features of Prader-Willi syndrome
* **Constant insatiable hunger** that leads to **obesity**
* Hypotonia in infancy *(which can make feeding difficult in infancy)*
* Mild-moderate learning disability
* Hypogonadism
* Infertility
* Short stature
* Fairer, soft skin that is prone to bruising
* Dysmorphic features
* Narrow forehead
* Almond shaped eyes
* Strabismus
* Thin upper lip
* Downturned mouth
* Mental health problems, particularly anxiety
44
Discuss the management of Prader-Willi syndrome
Management is centred around supporting symptoms/features via MDT:
* Weight control under guidance of dietician
* Limiting access to food (in all settings including school) e.g. locks on doors
* Lower than normal calorie intake (as tend to have lower activity level due to poor muscle strength & tone)
* Growth hormone *(recommended by NICE to improve muscle development & body composition)*
* Physiotherapists
* OTs
* Psychologists or psychiatrists
* Suuprot worker
* Educational support
45
What genetic mutation occurs in Angelman syndrome?
* **Loss of function of the UBE3A gene on the maternal chromosome 15**. Could be caused by **deletion (most common), a specific mutation in the gene or if two copies of chromosome 15 are inherited from the father**
* \*\*\*\***People normally inherit one copy of the* *UBE3A* *gene from each parent. Both copies of this gene are turned on (active) in many of the body's* *tissues**. In certain areas of the brain, however, only the copy* *inherited* *from a person's mother is active*
46
State some features of Angelman syndrome
* **Fascination with water**
* **Happy demeanour**
* **Wide mouth with widely spaced teeth**
* Delayed development and learning disability
* Severe delay or absence of speech development
* Coordination and balance problems (ataxia)
* Inappropriate laughter
* Hand flapping
* Abnormal sleep patterns
* Epilepsy
* Attention-deficit hyperactivity disorder
* Dysmorphic features
* Microcephaly
* Fair skin, light hair and blue eyes
47
Discuss the management of Angelman syndrome
Management focused on treating symptoms/features via MDT; involves:
* Anti-epileptic medications where required
* Physiotherapy
* Occupational therapy
* CAMHS involvement
* Psychology input
* Educational support
48
What genetic mutation occurs in William syndrome?
**Deletion of genetic material on one copy of chromosome 7** (hence individual only has a single copy of the genes in the deleted region).
49
State some features of William's syndrome
* Broad forehead
* **Starburst eyes** (a star-like pattern on the iris)
* **Wide mouth with widely spaced teeth and big smile**
* **Very sociable trusting personality**
* Flattened nasal bridge
* Long philtrum
* Small chin
* Mild learning disability
* Short stature
50
William's syndrome is associated with other conditions; state some
* **Supravalvular aortic stenosis** (narrowing just above the aortic valve)
* **Hypercalcaemia**
* Attention-deficit hyperactivity disorder
* Hypertension
51
Discuss the management of William's syndrome
Management centred around treating symptoms/features and complications; involves MDT management. Specific examples of management plan include:
* ECHO & BP monitoring (aortic stenosis & hypertension)
* Low calcium diet
52
What is meant by genetic anticipation?
With genetic anticipation, hereditary diseases have an earlier age of onset through successive generations.
Examples:
* Fragile X syndrome
* Huntington's disease
* Myotonic dystrophy
53
For Edward's syndrome, discuss:
* Chromosomal abnormality
* Clinical features
* Prognosis
* Trisomy 18
* Features:
* Micrognathia
* Low set ears
* Rocker bottom feat
* Overlapping fingers
* Clenched fists
* Abnormalities of organs
* Intrauterine growth retardation
* Only a small number of babies born alive with Edward's syndrome will live past 1yr
54
For Pierre-Robin syndrome, discuss:
* Features
* Micrognathia
* Posterior displacement of tongue that may result in upper airway obstruction
* Cleft palate
55
For Cri du chat syndrome, discuss:
* Genetic mutation
* Features
* Chromosome 5p deletion syndrome
* Features:
* Characteristic cry due to larynx & neurological problems
* Feeding difficulties & poor weight gain
* Learning difficulties
* Microcephaly
* Micrognathism
* Hypertelorism
56
For CHARGE syndrome, discuss:
* Mutation
* Inheritance pattern
* Features
* CHD7 gene mutations
* Autosomal dominant
* Features:
* Coloboma & cranial nerve abnormalities
* Heart defects
* Atresia choanae
* Retardation of growth
* Genital abnormalities
* Ear abnormalities
57
For Treacher-Collins syndrome, discuss:
* Mutations and modes of inheritance (not asking specifics)
* Features
* Different mutations have different modes of inheritance!
* Features:
* Downward drooping eyes
* Micrognathia
* Very small or absent ears
* Cleft palata
* Coloboma *(**a hole in one of the structures of the eye)*
Yr4: Child Health
flashcards
Decks in class (21)
# Cards
-
Community Paediatrics66
-
Child Development85
-
Safeguarding & Law20
-
Endocrinology100
-
Respiratory 191
-
Respiratory 248
-
ENT45
-
Cardiology121
-
Paediatric Emergencies36
-
Neurology90
-
Infectious Diseases92
-
Gastroenterology59
-
Surgery111
-
Haematology/oncology85
-
Neonatology132
-
Musculoskeletal/Rheumatology107
-
Renal & Urology57
-
Immunology42
-
Paediatric History & Examination19
-
Genetics57
-
Dermatology80
