Genetics and Syndromes Flashcards
What are the main aims of genetic counselling?
SUpport + education;
Understand the situation
Make own decisions about managing risk
What are some other aims of genetics counselling?
Listen to concerns of family Establish correct diagnosis Risk estimation Communication - written info good Options for Mx and prevention
What is a malformation
Structural defect of development
What is a deformation
Intrauterine mechanical force that distorts normal structures
What is disruption
Destruction of parts that were normal
What is dysplasia
Abnormal structure, function of specific tissue
Common features in Noonans
Pulmonary stenosis Webbed neck Short stature Broad forehead Wide eyes (down slant) Low ears
Common features in Williams
Short stature V friendly Learning difficulties Supravalvular aortic stenosis Neonatal hypercalcaemia Upturned nose, wide eyes, small chin, slightly puffy cheeks
Common Features Prader-WIlli syndrome
Almond eyes Narrow forehead temples Narrow nose Thin lips Decr tone Decr gonad Incr appetite
How much alcohol are women recommended to drink in pregnancy ?
Recommended to abstain
If they do drink - no > 1-2 units 1-2x week
What is the triad of foetal alcohol syndrome?
Growth failure
Craniofacial abnormalities
Neurodevelopment
Growth failure in FOS
Decr Weight
Decr length
Stunted for life
Craniofacial abnormalities in FOS (6)
Microcephaly Flat philtrum Thin upper lip Ptosis Cleft lip/palate Posterior rotation of ears
Neurodevelopment issues in FOS (5)
Decr IQ ADHD Memory issues Poor social skills/problem solving/co-ordination S+L delay
Gene problem in Fragile X syndrome
Expansion of repeat seq in FMR1 gene
Proportion males w/ fragile X syndrome
1/4000
Proportion females w/ fragile X syndrome
1/8000
How does fragile X syndrome affect life expectancy?
It doesnt
Presentation Fragile X syndrome
Low IQ <70 Delayed milestones Anxiety High forehead, large testes, facial asymmetry, large jaw, long ears Changes in connective tissue Social withdrawal Clumsiness, avoidance by gaze
What does changes in connective tissue lead to in Fragile X syndrome? (3)
Prominent ears, hyperexensible finger joints, mitral valve prolapse
@ What age is diagnosis of Fragile X usually made by?
3
Mx Fragile X (5)
SALT Special education ADHD Tx if req SSRI's (anxiety) Genetic counselling
What is Marfans?
AD connective tissue disorder
Mis-sense mutation in Fibrilin 1 gene
Presentation Marfans (10)
Tall + thin w/ long arms/legs Long fingers/toes Striae --> thoracocolumbar PLeural rupture --> pneumothorax Lens dislocation Joint instability Kyphosclosiosis Lower back pain Long face
CV complications in Marfans (4)
Aortic dilatation/dissection
Aortic regurg
Mitral valve prolapse
Mitral regurg
Main cause of death in Marfans
CV
How has life expectancy been increased in Marfans?
Propranolol
Surgery
Genetics of Rett’s syndrome
X linked
MECP2 gene mutation
@ What age does Rett’s start occuring
6-18 months
What 1/x births does Rett’s occur in
1/10,000
Presentation Rett’s
Developmental arrest Gross motor delay Hypotonia Loss eye contact Decr growth
Rett’s @1-4 y/o
Rapid developmental delay/regression
Rett’s @ 2-10 y/o
Stationary phase
Incr in behaviour, communication + hand use
Retts >10 y/o
Late motor deterioration
Genetic mutation in Duchenne’s MD
Deletion on short arm of x @ Xp21
–> decr dystrophin –> myofibre necrosis
S+S DMD
Waddling gait Delayed motor milestones Lanaguage delay Gowers sign Pseudohypertrophy of the calves
What is Gower’s sign
Using hands to walk up body from squatting position
What is Pseudohypertrophy of the calves
Replacement of mm by fat
@ What age will boys not be mobile if they have DMD?
10-14
Common co-morbidity DMD
Scoliosis
@ what point would you consider screening for DMD?
If boy not walking by 18 months
Initial Ix DMD
CK - x10-100> from normal @birth
Diagnosis of DMD (3)
Genetic analysis
MM biopsy - assay for Dystrophin protein decr
Clinical observation - mm strength + fct
Mx DMD (9)
Exercise for power + mobility Passive stretching - prevent contractures Good sitting - scoliosis Truncal brace - Mx scoliosis CPAP Corticosteroids 10days/month Vit D + Ca Review @ regional centre Support groups
LE DMD
20s
Why do people w/ DMD die early
Resp failure/cardiomyopathy
What part of the embryo does the nervous system + skin come from?
Ectoderm
What is neurofibromatosis?
Genetic disorder –> lesions skin, skeleton + MS
AD New mutations (hence no FHx)
Prevalence NFM-1
1/4000
What is NFM-1
Loss of neurofibromin (TS) –> incr risk developing benign/malig tumours
Diagnostic criteria NFM-1
2 of >: Cafe-au-lait spots 6+ >1 neurofibroma Axillary freckles Optic glioma Lisch nodule Sphenoid dysplasia 1st degree relative w/ NFM-1
Prevalence NFT-2
1/100,000
When does NFT-2 present
In adolescence
which has a worse prognosis - NFT1 or 2
2
Diagnostic criteria NFT-2
at least 1 of Bilat CNVIII on MRI (acoustic neuroma) 1st degree relative w/ NF2 + unilat CNVIII mass 1st degree relative w/ NF-2 + 2 of: > Meningioma > Glioma Schwannoma > Juvenile cataracts
Consequence of bilateral acoustic neuromas in NFT-2
Deaf
What are both types of NFT associated with
Endocrine disorders - MEN syndrome
Features of MEN syndrome
PCC
Pulm HoTN
Renal aa stenosis
Gliomatous changes
Genetics of tuberous sclerosis
AD TSC1/2 gene mutation
Codes of hamartin + tuberin
Cutaneous features of Tuberous sclerosis (3)
Ash leaf patches that fluoresce in UV
Rough patches skin over lumbar spine
Adenoma in butterfly distribution over face
Neuro features of Tuberous sclerosis (4)
Infantile spasm
Developmental delay
Epilepsy
Intellectual impairment
What is the most common form of short-limb dysplasia
Achondroplasia
RF achondroplasia
Paternal age
CF achondroplasia (4)
V short arms + legs
Narrow chest
Broad limbs
Small face/flat nasal bridge
LT problems achondroplasia
Short stature Disability in arm fct/locomotion Kyphosis OA Spinal stenosis Obesity ENT - OM, URTI, deafness, apnoea
LE in achondroplasia
Normal
Genetic issue in PKU
Absent PAH enzyme activity –> incr phenyalanine –> neurotoxic byproducts
Hence, what will occur in PKU within the 1st year
Learning disability
Diagnosis of PKU is made on
Most - heel prick Fair + pale blue eyes b/c no melanin Incr developmental delay Vomiting Musty odour Eczemous skin eruptions Seizures Self mutilation
Mx PKU
Metabolic clinic - protein restricted
Prognosis PKU
Excellent if adhere to diet + intelligence becomes normal
How is PKU screened
In Guthrie
