Genetic Neurodegenerative Disease + Congenital Flashcards
What is neurofibromatosis
AD condition that causes tumours (neuroma) to develop
Benign but can cause neuro./ structural Sx
Two types
NF1 - 17q tumour suppressor
NF2 - chromosome 22
What is criteria for NF1
CRABBING Cafe au lait 6+ >5mm in children or >15mm in adults Relative with NF1 Axillary or inguinal freckles Bony dysplasia Iris haemartoma 2+ (Lisch nodules) - yellow spot on iris Neurofibroma 2+ Glioma of optic nerve - decreased vision
What is needed to indicate Dx
What are other features
2/7 Macrocephaly Short stature Dysmorphism Epilepsy LD Scoilosis Raised BP due to renal artery stenosis GI / brain / spinal cord / leukaemia
How do you investigate
Clinical Genetic if doubt X-ray for bone pain / lesions CT / MRI BP Spine X-ray Visual acuity and field
What does NF2 present with
Bilateral vestibular schwanoma
Mengioma
Ependyoma
GLioma
How is tuberous sclerosis inherited and how do you screen at risk
AD TSC1 and TSC2 Surveillance Cranial MR Renal US ECHO FUndoscopy
What does it cause
Development of haemartoma = classic feature which affects different areas
- Brain
- Retina
- Kidney
- Skin
Skin Ash leaf spots - depigmentated macule Rough skin over L spine (Shagreen) Angiofibroma Subungal Fibromata beneath nails Cafe au lait
Neuro
Development delay
Epilepsy - infantile spasm
Intellectual impairment
What are complications / other features
Rhabdomyoma of heart - malignancy Glioma's in brain Retinal haematoma PCKD Angiomyolipoma in kidney Multiple lung cyst
What is classic presentation
Child with epilepsy + skin features
Triad of epilepsy, LD and skin
How is Huntington’s inherited and what is the mutation
AD
Fully penetrant
CAG expansion on chromosome 4
Leads to excess glutamine
What type of disorder
Trinucleoside
Leads to anticipation
What is anticipation
Age of onset reduces and more severe with each generation affected
- Huntington’s
- Fredreich
What is age of onset
Adult
Late 30’s / 40’s
What is pathology
Severe atrophy of striatum affecting basal ganglia
Responsible for initiating and preventing unwanted movement
Also role in cognition and emotion
What are features
Movement disorder
Cognitive change
Persoanlity change
Psychaitric
What are movement disorder
Chorea = characteristic excessive spontaneous movement Athetosis Dystonia Bradykinesia Eye - rapid eye movement = early sign Myoclonus Rigid Dysarthria Dysphagia
What is cognitive change
Subcortical dementia
Poor memory
Executive most affected - planning / attention
When does cognitive change occur
Early
What are personality changes
irritable
Apathetic
Disinhibition
Self centered
When does personality change occur
Early
What are psychiatric
Depression
Paranoia
Psychosis
Schizophrenia
What is usual cause of death
Become more susceptible to infection
Suicide
How do you Dx
Clinical signs
Neuropsychology
How do you treat
Supportive SALT Dietician Symptom relief Must inform DVLA POA before cognitive decline
What testing is available
Pre-natal
Pre-implantation if IVF
What is lissencephaly
Smooth brain as gyri and sulci fail to form
What are Sx
FTT
Mental impairment
Seizure
Abnormal muscles
What is polymicrogyria and presentation
Excessive small gyri
Mental retardation and seizure
What is microcephaly
Head OCF <2 centile
What can cause
Normal variation / familial Congenital infection - ZIKA Perinatal injury - HIE FAS / drugs Syndrome e.g. Patau Craniosyntosis
What is porencephaly and Sx
CSF filled cyst
Mental retardation, FTT and seizure
What is schizencephaly and what causes
Large clefts of cysts in brain
Stroke / infection / genetics
How does it present
Mental retardation, FTT, paralysis and seizure
What is diastolematomyelia
Spinal cord split into 2 parts
What are the Sx
Vertebral anomalies
Scoliosis and foot defmmority
Weakness
What is anencephaly
Failure of anterior neuropore to close
Skull fails to form and brain tissue degenerates
Incompatible with life
What is encephalophoele
Part of neural tube doesn’t form leaving gap in skull which spinal cord can herniate through
What is spina bidifa oculta
Failure of embryonic halve of vertebral arch to fuse
L5 / L6
Sx
Usually none
What are types of spina bifida cystica
Meningocele
Meningomyecele
Myeloschsis
Meningocele
Mildest
Protrusion of meninges
Nerves unaffected
Menigomyecele
Herniation of neural root and cord leading to Sx
What is it associated with
Arnold chairi
Acqueduct stenosis
Cauda equina
What is myeloschisis
Spina cord open = paralysis and no sensation
How do you prevent
Folic acid
Screen amniocentesis + USS
What suggests
High AFP
