Genetic conditions Flashcards
What is Klinefelter syndrome
When a male has an additional X chromosome making them 47 XXY
Give 5 clinical features of Klinefelter syndrome
- Taller height
- Infertility
- Gynaecomastia (swelling)
- Small testes
- Subtle learning difficulties - speech and language
How is Klinefelter syndrome managed
- testosterone injections
- Breast reduction surgery
- advanced IVF techniques to allow fertility
Give 3 complications of Klinefelter syndrome
- diabetes
- breast cancer
- osteoporosis
What is turners syndrome
chromosomal disorder involving a complete or partial absence of the second X chromosome in females making them 45 XO
Give 6 clinical features of turners syndrome
- short stature
- neck webbing
- widely spaced nipples
- lymphoedema in neonates
- delayed/ incomplete puberty (primary amenorrhoea)
- underdeveloped ovaries with reduced function (infertility)
Give 4 conditions associated with turners syndrome
- bicuspid aortic valve
- coarctation of the aorta
- hypothyroidism
- aortic dissection and dilation
How is turners syndrome managed
- Growth hormone therapy
- Oestrogen replacement can help establish female secondary sex characteristics
- Monitoring for associated conditions
What is the main inheritance pattern of Noonan syndrome
Autosomal dominant
Give 6 features of Noonan syndrome
- Short stature
- wide-spaced down-slanting eyes
- webbed neck
- low-set posteriorly rotated ears
- pectus excavatum
- wide-spaced nipples
Give 4 conditions associated with Noonan syndrome
- Congenital heart disease
- Cryptorchidism (undescended testes)
- bleeding disorders (factor XI deficicency)
- learning difficulties
What 3 congenital heart conditions are common in children with Noonan syndrome
- Hypertrophic cardiomyopathy
- atrial septal defect
- pulmonary valve stenosis
How is Noonan syndrome managed
- supportive management with MDT
- corrective heart surgery is often needed for congenital HD
What causes fragile X syndrome
trinucleotide repeat disorder on the X chromosome
Inheritance pattern of fragile X syndrome
X linked but unclear whether it is dominant or recessive
- females are affected variably
Give 5 features of fragile X syndrome
- Large testicles after puberty
- Long, narrow face
- large posteriorly everted ears
- moderate-severe learning difficulties
- hypermobile joints
- mitral valve prolapse
What is Prader-Willi syndrome
A genetic condition caused by the absence of the active prader-willi gene on the long arm of chromosome 15
Prader-Willi syndrome typically occurs due to one of two main genetic mutations. State these in relation to PWS
- Paternal deletion of involved genes (mc)
- maternal uniparental disomy - two copies of chromosome 15 inherited from mother
Give 5 clinical features of Prader-Willi syndrome
- Constant insatiable hunger leading to obesity (starting in older child)
- central hypotonia
- Neonatal feeding difficulties
- hypogonadism
- developmental delay and learning difficulties
Give 2 symptoms associated with hypotonia in neonates with PWS
- weak cry
- poor suck
Give 4 physical features that may be seen in a person with PWS
- almond-shaped face
- narrow forehead
- Thin upper lip
- small hands and feet, short stature
How is Prader-Willi syndrome managed
MDT management: dietician, endocrinologists, physios, psychiatrist
* management of access to food - locks on fridge/ cupboards
* Growth hormone treatment in first year of life - improve muscle development and body composition
What is Angelman syndrome
genetic condition caused by a mutation or deletion in the UBE3A gene on chromosome 15
Angelman syndrome typically occurs due to one of two main genetic mutations. State these relative to Angelman
- deletion of UBE3A gene from maternal chromosome 15 (mc)
- uniparental disomy - person inherits two copies of chromosome 15 from father (no maternal copies)
Give 6 features of Angelman syndrome
- Unusual fascination with water
- happy demeanour and inappropriate laughter
- epilepsy
- abnormal sleep patterns
- ataxia
- microcephaly
- wide mouth with wide-spaced teeth
- severe cognitive impairment and developmental delay - specifically speech
What causes william syndrome
sporadic deletion of genetic material on one copy of chromosome 7 resulting in only a single copy of genes
Give 6 clinical features of William syndrome
- very sociable trusting personality
- starburst eyes (iris)
- wide mouth with a big smile
- short upturned nose
- small chin
- mild-moderate learning difficulties
Give 3 conditions associated with William syndrome
- Supravalvular aortic stenosis
- transient neonatal hypercalcaemia
- peripheral pulmonary artery stenosis
What causes down syndrome
trisomy 21 - 3 copies of chromosome 21
Give 6 characteristic facies of down syndrome
- small and flat head with round face
- flat nasal bridge
- brushfield spots in iris
- small ears and short neck
- upslanted palpebral fissures
- epicanthic folds - skin fold of upper eyelid that covers the inner corner of the eye
- small mouth and protruding tongue
Give 2 gastrointestinal conditions associated with down syndrome
- duodenal atresia
- Hirschsprung’s disease
Apart from characteristic facies, give 5 other clinical features of down syndrome
- hypotonia
- single palmar crease
- developmental delay
- congenital heart defects
- duodenal atresia
- wide gap between first and second toe
The incidence of trisomy 21 due to nondisjunction is related to what risk factor
maternal age - older maternal age at conception influences chromosome segregation in the eggs
How is down syndrome diagnosed
- antenatal screening - risk assessment
- chromosomal karyotype analysis
Give 4 things children with down syndrome should be screened for periodically
- Vision
- Hearing
- hypothyroidism
- cardiac defects
How is down syndrome managed
- MDT approach - SALTs, cardiologist, physio
- regular screening of complications
- genetic counselling
- early intervention for development
Give 6 later complications of down syndrome
- subfertility
- Alzheimer’s disease
- obstructive sleep apnoea - snoring
- repeated respiratory infections (+hearing impairment from glue ear)
- short stature
- acute lymphoblastic leukaemia
- hypothyroidism
- atlantoaxial instability - increased risk of neck dislocation
Give 5 cardiac complications of down syndrome
- endocardial cushion defect
- VSDs
- ASDs
- ToF
- isolated patent ductus arteriosus
What is the most common form of congenital heart disease in down syndrome
atrioventricular septal defect
What chromosome abnormality is associated with Edwards syndrome?
trisomy 18
Give some key features of Edwards syndrome
- Micrognathia (small jaw/ chin)
- Low-set ears
- Rocker bottom feet
- flexed, overlapping of fingers
What chromosome abnormality is associated with patau syndrome
trisomy 13
Give some key features of patau syndrome
- Microcephalic (small head), small eyes
- Cleft lip/palate
- Polydactyly
- Scalp lesions
What is Duchenne muscular dystrophy
X-linked recessive inherited disorder affecting the dystrophin genes, essential for normal muscle function
What are the key features of Duchenne muscular dystrophy?
- Progressive proximal muscle weakness starting around age 5
- abnormal gait/ delayed motor milestones
- calf hypertrophy
- Gower’s sign
- intellectual impairment
Describe the process of Gower’s sign.
To perform Gower’s sign, a child:
- Gets onto hands and knees.
- Pushes hips up and backwards.
- Shifts weight backwards and moves hands to knees.
- Walks hands up legs to stand, keeping legs mostly straight.
Why do children with proximal muscle weakness use Gower’s sign?
the muscles around the pelvis are not strong enough to elevate their upper body without the help of their arms.
How is Duchenne muscular dystrophy investigated?
- raised serum creatinine kinase levels
- genetic testing
What is the management approach for Duchenne muscular dystrophy?
largely supportive
* corticosteroids (prednisolone) to help preserve mobility and prevent scoliosis
* physiotherapy and exercise to maintain muscle power and mobility
* wheelchairs/ night splints
What is the prognosis for children with Duchenne muscular dystrophy?
- Most children cannot walk by age 12
- typically survive to around 25-30 years
- associated with dilated cardiomyopathy and respiratory failure
