Genetics II Flashcards
Describe the pathophysiology of Fragile X syndrome [1]
Fragile X syndrome is caused by a mutation in the FMR1 (fragile X mental retardation 1) gene on the X chromosome
- The FMR1 gene codes for the fragile X mental retardation protein, which plays a role in cognitive development in the brain.
NB: It is X-linked, but it is unclear whether it is dominant or recessive.
What are the clinical features of Fragile X syndrome [+]
Fragile X syndrome usually presents with a delay in speech and language development. Other features are:
- Intellectual disability
- Long, narrow face
- Large ears
- Large testicles after puberty
- Hypermobile joints (particularly in the hands)
- Attention deficit hyperactivity disorder (ADHD)
- Autism
- Seizures
TOM TIP: The key feature everyone remembers for Prader-Willi syndrome is the the [].
TOM TIP: The key feature everyone remembers for Prader-Willi syndrome is the the insatiable hunger
What is the pathophysiology of Prader-Willi Syndrome? [1]
Prader-Willi Syndrome is a genetic condition caused by the loss of functional genes on the proximal arm of the chromosome 15 inherited from the father. This can be due to a deletion of this portion of the chromosome, or when both copies of chromosome 15 are inherited from the mother.
What are the clinical features of Prader-Willi syndrome? [+]
- Constant insatiable hunger that leads to obesity
- Poor muscle tone as an infant (hypotonia)
- Mild-moderate learning disability
- Hypogonadism
- Fairer, soft skin that is prone to bruising
- Mental health problems, particularly anxiety
- Dysmorphic features
- Narrow forehead
- Almond shaped eyes
- Strabismus
- Thin upper lip
- Downturned mouth
[] is indicated by NICE as a treatment for Prader-Willi Syndrome, aimed at improving muscle development and body composition.
Growth hormone is indicated by NICE as a treatment for Prader-Willi Syndrome, aimed at improving muscle development and body composition.
Describe the difference in pathophysiology between Prader-Willi and Angelman syndrome [2]
Prader-Willi syndrome if gene deleted from father
- from chromosome 15
Angelman syndrome if gene deleted from mother
- UBE3A gene from chr 15
Features of Angelman Syndrome? [+]
TOMTIP features? [3]
Delayed development and learning disability
Severe delay or absence of speech development
Coordination and balance problems (ataxia)
Fascination with water
Happy demeanour
Inappropriate laughter
Hand flapping
Abnormal sleep patterns
Epilepsy
Attention-deficit hyperactivity disorder
Dysmorphic features
Microcephaly
Fair skin, light hair and blue eyes
Wide mouth with widely spaced teeth
TOM TIP: The novel features to remember and link with Angelman syndrome so you can spot it in your exams is the unusual fascination with water, happy demeanour and widely spaced teeth.
Describe the pathophysiology of William syndrome [1]
William syndrome is caused by a deletion of genetic material on one copy of chromosome 7, resulting in the person only having a single copy of the genes on this deleted region (on the other chromosome 7). It usually the result of a random deletion around conception, rather than being inherited from an affected parent.
Describe the clinical features of William syndrome [+]
Include TT [5]
- Broad forehead
- Starburst eyes (a star-like pattern on the iris)
- Flattened nasal bridge
- Long philtrum
- Wide mouth with widely spaced teeth
- Small chin
- Very sociable trusting personality
- Mild learning disability
TOM TIP:
- The distinctive features to remember with William syndrome are the very sociable personality, the starburst eyes and the wide mouth with a big smile. It is worth remembering the association with supravalvular aortic stenosis and hypercalcaemia, as these are unique features that are easy to test in exams.
What are the associated conditions of William syndrome/ [4]
Supravalvular aortic stenosis (narrowing just above the aortic valve)
Attention-deficit hyperactivity disorder
Hypertension
Hypercalcaemia
This eye would suggest which syndrome? [1]
Sunburst eye - Williams
