Genetics and Syndromes Flashcards
How does Trisomy 21 occur?
Meiotic non-disjunction
- error in meiosis where one pair of chromosomes fail to separate
- fertilisation adds another chromosome 21 to make three
- related to maternal age
Translocation
- extra chromosome 21 is attached to another chromosome (14, 15, 22 or 21)
- parents are carriers of this type
Mosaicism
- some cells are normal and some have Trisomy 21
What are the clinical features of Down’s syndrome?
round face and flat nasal bridge epicanthic folds small mouth and protruding tongue small ears flat occiput and third fontanelle hypotonia
What is Down’s syndrome associated with?
Congenital heart defects - AVSD and VSD Duodenal atresia Hirschsprung disease Small stature Increased susceptibility to infection Hearing impairments Cataracts, squints and myopia Increased risk of solid tumours and leukaemia Epilepsy Alzheimers
How is Down’s syndrome screened and investigated?
All pregnant women offered screening - biochemical markers in blood and nuchal thickening on USS
Amniocentesis of fetal chromosomal pattern
Blood is sent for FISH technique
How does Turner’s syndrome arise?
> 95% result in early miscarriage - males are incompatible with life
Antenatal USS shows fetal oedema of neck, hands, feet or cystic hygroma
Deletion of entire X chromosome, short arm etc.
What are the clinical features of Turner’s syndrome?
Shorter than average
Lack of ovary development –> infertility
Lymphoedema of hands and feet Neck webbing Wide spaced nipples Coarctation of the aorta Hypothyroidism Renal anomalies
What are the long term complications and treatment of Turner’s syndrome?
Heart murmur Underactive thyroid HTN Osteoporosis Scoliosis Diabetes
Given GH and oestrogen/progesterone replacement
What is Duchenne’s Muscular Dystrophy and how is it inherited?
Affects males
X-linked recessive deletion of dystrophin protein
Dystrophin links muscle fibre to surrounding matrix
What are the clinical features of DMD?
Waddling gait +/- language delay
Selective atrophy of muscle - sternal head of pec major and brachioradialis
Pseudohypertrophy of calves
Boys are slower and more clumsy than peers
No longer ambulant by 10-14yo
Life expectancy is late teens by respiratory failure
How is DMD diagnosed?
Blood test shows elevated creatine kinase
Muscle biopsy
How is DMD managed?
Exercise to maintain muscle power, mobility and delay onset of scoliosis
Splints
Respiratory aids
Corticosteroids
How does Noonan syndrome present?
AUTOSOMAL DOMINANT
Short stature Broad forehead Wide eye distance Drooping eyelids Low-set ears Small jaw Webbed neck Low hairline
How does Williams syndrome present?
DELETION of Ch 7
Elfin face
Heart defect
Very sociable
How does Prader-Willi syndrome present?
DELETION of Paternal Ch 15
Insatiable appetite –> obesity
How does neurofibromatosis type 1 present?
Autosomal dominant, 1 in 3000 births
Benign tumours of peripheral nerves
Cafe-au-lait spots
Neurofibroma
Axillary freckles
Optic glioma
Become more apparent during puberty
May cause visual or auditory impairment
How does neurofibromatosis type 2 present?
Autosomal dominant, 1 in 25,000
Causes CNS lesions
Bilateral acoustic neuromata
facial nerve paralysis
What other conditions are neurofibromatosis associated with?
Multiple endocrine neoplasia syndrome
Phaeochromocytoma
Pulmonary hypertensio
Renal artery stenosis with HTN
How does tuberous sclerosis present?
Dominantly inherited, 1 in 9000
Ash leaf patches which fluoresce under UV light
Facial angiofibromas
Rough patches (shagreen) over lumbar spine
Cardiac rhabdomyoma
Infantile spasms
Epilepsy
Intellectual impairment
How does achondroplasia present?
Inherited autosomal dominant condition - but 50% are new mutations
Short stature from limb shortening Large head Frontal bossing Lumbar lordosis Hydrocephalus
How does alcohol affect the fetus?
Facial abnormalities
IUGR
Cognitive impairment- hyperactivity, epilepsy, delirium tremens
MSK and urogenital deformities
How does Fragile X syndrome present?
Developmental milestones are normal in infancy but then there are speech and language delays
Commonly autistic-like symptoms
Large, protruding ears and testes
How does Marfan’s present?
Disproportionally tall and thin with long arms and legs
Skin - striae CV - thoracic duct dilatation/rupture/dissection. AAA Eyes - high myopia Joints - hypermobile, arthralgia Skeleton - pectus excavatum
What is PKU?
Body is unable to break down phenylalanine which builds up in blood and brain —> learning difficulties, epilepsy, fair hair and skin
If treated early with low protein diet and avoding aspartame then there are no problems
How does Rett’s sydrome present?
GIRLS
6-18 months - gross motor delay, loss of eye contact
1-4 years - decreased head circumference, loss of communication, autism like behaviours
Stationary phase
2-10 years - small improvement in social interactions and communication
>10 years - dystonia, hypertonia and Parkinsonism, no walking, breathing abnormalities
What is Down’s syndrome?
Trisomy 21
What is Patau syndrome?
Trisomy 13 - females
What is Edward’s syndrome?
Trisomy 18 - females
What is Turners syndrome?
XO
What is Williams syndrome?
Chromosome 7
What is Prader-Willi?
Paternal chromosome 15
What is Angelman syndrome?
Maternal chromosome 15
What is cris du chat syndrome?
Chromosome 5
What is Klinefelter’s syndrome?
XXY
How does Patau syndrome present?
Microphthalmia Polydactyly Rocker bottom feet Kidney defects Heart defects - VSD, PDA
How does Edwards syndrome present?
Clenched hand and overlapping fingers
Small jaw, cleft lip, microcephaly
Polyhydramnios
Heart defect - VSD, ASD, PDA
