Neurogenetic disorders Flashcards
What chromosomal abnormality is responsible for the development of myotonic dystrophy?
- Expansion of an unstable trinucleotide repeat on chromosome 19
- contains the DMPK gene encoding for myotonin protein kinase
What is the inheritance pattern of myotonic dystrophy?
Autosomal dominant
**myotonic dystrophy also shows ANTICIPATION
What is the main feature of myotonic dystrophy, as a result of a defect on chromosome 19?
Abnormally sustained muscle contraction after voluntary contraction ceases
What are the clinical features of myotonic dystrophy?
- Frontal balding
- Bilateral ptosis
- Facial weakness (myopathic facies)
- Wasting of temporalis and masseter
- Swan neck deformity (wasting + weakness of SCM)
- Proximal + distal muscle weakness
- Grip myotonia
- Dysarthria
- Cataracts
- many other clinical features
What is the main differential diagnosis for myotonic dystrophy?
Fascioscapulohumeral dystrophy :
- face and neck weakness
- winged scapula
- hypertrophy of deltoids
What investigations should be performed for myotonic dystrophy?
- Genetic testing (definitive)
- EMG
- Muscle biopsy
- Creatinine kinase (normal/mildly elevated)
- Blood glucose/HbA1c
- ECG
- CXR
- Slit lamp exam
What is are typical EMG findings in myotonic dystrophy?
- Dive bomber patter
- Waxing and waning of potentials
- Repetitive discharges with minor stimulation
What are the management options for myotonic dystrophy?
- MDT approach
- Medical management: phenytoin, quinine, procainamide, mexiletine (for myotonia)
- Surgical management: cataract removal, pacemaker for heart block etc
- Screen relatives
What chromosomal abnormality is responsible for the development of Huntington’s disease?
Abnormal expansion of CAG trinucleotide in the huntingtin gene (chromosome 4)
- Pathological if there are >36 repeats
What is the inheritance of Huntington’s disease?
- Autosomal dominant
- Shows anticipation
What are the motor features of Huntington’s disease?
- Progressive chorea
- Parakinesia
- Dysphagia and dysarthria
- Dystonia
- Parkinsonian features (bradykinesia, rigidity)
- Eye movement disorders (saccadic eye movement)
What are the psychological features of Huntington’s disease?
- Depression
- Increased suicide risk
- Paranoia
- Delusions
- Irritability
- Agitation
- Sleep disturbance
- Cognitive impairment (progressive cognitive decline, dementia)
What is the investigation of choice for definitive diagnosis of Huntington’s disease?
Genetic testing
What are the differential diagnoses for Huntington’s disease?
- Dentarubropallidoluysian atrophy
- ADCA I
- Hallervorden-Spatz disease
- Neuroferritinopathy
What is the pharmacological management of Huntington’s disease?
- VM2 inhibitors (Tetrabenazine)
- Antipsychotics (Risperidone)
- Benzodiazepines (Clonazepam)
What are VMAT2 inhibitors, and why are they used in the management of Huntington’s disease?
- Vesicular monoamine transporter type 2 inhibitors
- Dopamine depleting agents
- Used to treat troublesome chorea
Why are anti-psychotics used in Huntington’s disease?
- Can be used for some of the psychiatric features of Huntington’s, but mainly used for chorea
What is the life expectancy with a diagnosis of Huntington’s?
15-20 years after symptom onside
What are the most common causes of death in Huntington patients?
- Respiratory disease (pneumonia)
- Suicide
What is the difference between Charcot-Marie-Tooth disease type 1 (CMT type 1) and type 2 (CMT type 2)?
CMT type 1:
- demyelinating form
- usually presents before age 30 years
- more severe form
CMT type 2:
- axonal form
- presents later and less severe
What is the inheritance pattern of Charcot-Marie-Tooth disease?
Autosomal dominant
- Some cases of CMT type 2 can be autosomal recessive
What are the clinical features of Charcot-Marie-Tooth disease?
- Pes cavus (high-foot arches)
- Distal muscle wasting (inverted champagne bottle legs)
- Foot drop
- Weakness in the hands
- Hyporeflexia
- Hypotonia
- Peripheral sensory loss
- Hammer toes or toe clawing
- Sensory ataxia
What are the causes of peripheral neuropathy?
A - Alcohol B - B12 deficiency C - Cancer and CKD D - Diabetes and drugs (isoniazid, amiodarone, and cisplatin) E - Every vasculitis
What investigations should be performed for Charcot-Marie-Tooth disease?
- Genetic testing
- Clinical examination
- Nerve conduction studies
What are the differential diagnoses for Charcot-Marie-Tooth disease?
- Diabetic neuropathy
- Chronic inflammatory demyelinating polyneuropathy
- Acquired peripheral neuropathy
- Hereditary spastic paraplegia
- Spinocerebellar degeneration
What genetic defect is responsible for the development of Duchenne’s muscular dystrophy?
Caused by a defective gene for dystrophin on the X chromosome
What is the inheritance pattern of Duchenne’s muscular dystrophy?
X-linked recessive
What investigations should be performed for Duchenne’s muscular dystrophy?
- Genetic testing (definitive)
- Creatinine kinase
- Muscle biopsy
