What is Klinefelter syndrome?
When a male has an additional X chromosome making them 47 XXY instead of 46 XY.
Sx of Klinefelter syndrome?
Usually males look normal until puberty where they can develop:
* Taller height
* Wider hips
* Gynaecomastia
* Weaker muscles
* Small testicles
* Reduced libido + infertility
* Shyness
Mx of Klinefelter syndrome?
- Testosterone injections
- Breast reduction surgery - cosmetic purposes
Prognosis + complications of Klinefelter syndrome?
Life expectancy = normal
Inc. risk of:
* Breast cancer (compared to other males)
* Osteoporosis
* Diabetes
* Anxiety + depression
What is Turner syndrome?
When a female has a single X chromosome making it 45 XO instead of 46 XX.
O = empty space where other X chromosome should be.
Sx of Turner syndrome?
- Short stature
- Webbed neck
- Widely spaced nipples
- High arching palate
- Downward sloping eyes w/ptosis
- Cubitus valgus (abnormal elbow feature)
- Infertility
Associated cdtns with Turner syndrome?
- Recurrent otitis media
- Recurrent UTI
- Coarctation of the aorta
- Hypothyroidism
- HTN
- Obesity
- Diabetes
- Osteoporosis
Mx of Turner syndrome?
- Growth hormone therapy - prevent short stature
- Oestrogen + progesterone replacement - establish female characteristics + regulate period
- Fertility tx
What is Down’s syndrome?
Three copies of chromosome 21 (trisomy 21)
Sx of Down’s syndrome?
- Hypotonia
- Brachycephaly (flat head)
- Short neck
- Short stature
- Flattened face and nose
- Prominent epicanthic folds (folds of skin covering medial portion of eye + eyelid)
- Single palmar crease
What are the antenatal screening tests for Down’s syndrome?
- Combined test:1st line - Performed between 11 and 14 wks gestation, USS measures nuchal translucency (thickness back of neck of fetus, in DS the thickness >6mm)
- Triple test:performed between 14 and 20 wks gestation, involves maternal blood test results therefore: higher Beta-HCG, lower Alpha-fetoprotein and lower serum oestriol indicate greater risk of Down’s syndrome.
- Quadruple test:Identical to triple test but also icnludes maternal blood for inhibin-A (higher inhibin-A = greater risk)
When the previous test results provide a risk score of > 1 in 150, then further tests are done to give a definitive answer, which are:
* Chorionic villus sampling (CVS)
* Amniocentesis
Mx of Down’s syndrome?
Supportive care from the MDT and follow up Ix such as:
* Regular thyroid checks (2 yearly)
* Echo to diagnose cardiac defects
* Regular audiometry for hearing impairment
* Regular eye checks
What is Fragile X syndrome?
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.
What kind of genetic inheritance is Fragile X syndrome?
X-linked (unclear if dominant or recessive)
Sx of Fragile X syndrome?
- Intellectual disability
- Long, narrow face + large ears
- Large testicles after puberty
- Hypermobile joints (particularly in the hands)
- ADHD
- Autism
- Seizures
Ix for Fragile X syndrome?
Genetic test that detects number of CGG repeats in FMR1 gene.
Mx of Fragile X syndrome?
MDT support + behavioural therapy
What is Angelman syndrome?
Loss of function of the UBE3A gene specifically copy inherited from mother.
This can be caused by:
* Deletion on chromosome 15
* Specific mutation in this gene
* If two copies of chromosome 15 are contributed by father w/no copy from mother
Sx of Angelman syndrome?
- Unusual fascination w/water
- Happy demeanour
- Widely spaced teeth
- Delayed development + learning disability
- Severe delay + absence of speech development
- Inappropriate laughter
- Hand flapping
What is Prader-Willi syndrome?
Loss of functional genes on the proximal arm of the chromosome 15 inherited from the father.
This can be due to:
* Deletion of this portion of chromosome
* When both copies of chromosome 15 are inherited from the mother.
Sx of Prader-Willi syndrome?
- Constant insatiable hunger (obesity)
- Hypotonia
- Mild-moderate learning disability
- Hypogonadism
- Fairer, soft skin that is prone to bruising
- Narrow forehead
- Downturned mouth
Mx of Prader-Willi syndrome?
- Growth hormone - improves muscle development + body compisition
- Dietician
What is Noonan syndrome?
An inherited autosomal dominant cdtn.
Sx of Noonan syndrome?
- Short stature
- Broad forehead
- Hypertelorism (wide space between eyes)
- Downward sloping eyes w/ptosis
- Low set ears
- Webbed neck
