Neurogenetic disorders

Question 1

What chromosomal abnormality is responsible for the development of myotonic dystrophy?

Answer 1

• Expansion of an unstable trinucleotide repeat on chromosome 19
• contains the DMPK gene encoding for myotonin protein kinase

Question 2

What is the inheritance pattern of myotonic dystrophy?

Answer 2

Autosomal dominant

**myotonic dystrophy also shows ANTICIPATION

Question 3

What is the main feature of myotonic dystrophy, as a result of a defect on chromosome 19?

Answer 3

Abnormally sustained muscle contraction after voluntary contraction ceases

Question 4

What are the clinical features of myotonic dystrophy?

Answer 4

• 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

Question 5

What is the main differential diagnosis for myotonic dystrophy?

Answer 5

Fascioscapulohumeral dystrophy :

• face and neck weakness
• winged scapula
• hypertrophy of deltoids

Question 6

What investigations should be performed for myotonic dystrophy?

Answer 6

• Genetic testing (definitive)
• EMG
• Muscle biopsy
• Creatinine kinase (normal/mildly elevated)
• Blood glucose/HbA1c
• ECG
• CXR
• Slit lamp exam

Question 7

What is are typical EMG findings in myotonic dystrophy?

Answer 7

• Dive bomber patter
• Waxing and waning of potentials
• Repetitive discharges with minor stimulation

Question 8

What are the management options for myotonic dystrophy?

Answer 8

• MDT approach
• Medical management: phenytoin, quinine, procainamide, mexiletine (for myotonia)
• Surgical management: cataract removal, pacemaker for heart block etc
• Screen relatives

Question 9

What chromosomal abnormality is responsible for the development of Huntington’s disease?

Answer 9

Abnormal expansion of CAG trinucleotide in the huntingtin gene (chromosome 4)

• Pathological if there are >36 repeats

Question 10

What is the inheritance of Huntington’s disease?

Answer 10

• Autosomal dominant

- Shows anticipation

Question 11

What are the motor features of Huntington’s disease?

Answer 11

• Progressive chorea
• Parakinesia
• Dysphagia and dysarthria
• Dystonia
• Parkinsonian features (bradykinesia, rigidity)
• Eye movement disorders (saccadic eye movement)

Question 12

What are the psychological features of Huntington’s disease?

Answer 12

• Depression
• Increased suicide risk
• Paranoia
• Delusions
• Irritability
• Agitation
• Sleep disturbance
• Cognitive impairment (progressive cognitive decline, dementia)

Question 13

What is the investigation of choice for definitive diagnosis of Huntington’s disease?

Answer 13

Genetic testing

Question 14

What are the differential diagnoses for Huntington’s disease?

Answer 14

• Dentarubropallidoluysian atrophy
• ADCA I
• Hallervorden-Spatz disease
• Neuroferritinopathy

Question 15

What is the pharmacological management of Huntington’s disease?

Answer 15

• VM2 inhibitors (Tetrabenazine)
• Antipsychotics (Risperidone)
• Benzodiazepines (Clonazepam)

Question 16

What are VMAT2 inhibitors, and why are they used in the management of Huntington’s disease?

Answer 16

• Vesicular monoamine transporter type 2 inhibitors
• Dopamine depleting agents
• Used to treat troublesome chorea

Question 17

Why are anti-psychotics used in Huntington’s disease?

Answer 17

• Can be used for some of the psychiatric features of Huntington’s, but mainly used for chorea

Question 18

What is the life expectancy with a diagnosis of Huntington’s?

Answer 18

15-20 years after symptom onside

Question 19

What are the most common causes of death in Huntington patients?

Answer 19

• Respiratory disease (pneumonia)

- Suicide

Question 20

What is the difference between Charcot-Marie-Tooth disease type 1 (CMT type 1) and type 2 (CMT type 2)?

Answer 20

CMT type 1:

• demyelinating form
• usually presents before age 30 years
• more severe form

CMT type 2:

• axonal form
• presents later and less severe

Question 21

What is the inheritance pattern of Charcot-Marie-Tooth disease?

Answer 21

Autosomal dominant

• Some cases of CMT type 2 can be autosomal recessive

Question 22

What are the clinical features of Charcot-Marie-Tooth disease?

Answer 22

• 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

Question 23

What are the causes of peripheral neuropathy?

Answer 23

A - Alcohol
B - B12 deficiency 
C - Cancer and CKD
D - Diabetes and drugs (isoniazid, amiodarone, and cisplatin)
E - Every vasculitis

Question 24

What investigations should be performed for Charcot-Marie-Tooth disease?

Answer 24

• Genetic testing
• Clinical examination
• Nerve conduction studies

Question 25

What are the differential diagnoses for Charcot-Marie-Tooth disease?

Answer 25

• Diabetic neuropathy
• Chronic inflammatory demyelinating polyneuropathy
• Acquired peripheral neuropathy
• Hereditary spastic paraplegia
• Spinocerebellar degeneration

Question 26

What genetic defect is responsible for the development of Duchenne’s muscular dystrophy?

Answer 26

Caused by a defective gene for dystrophin on the X chromosome

Question 27

What is the inheritance pattern of Duchenne’s muscular dystrophy?

Answer 27

X-linked recessive

Question 28

What investigations should be performed for Duchenne’s muscular dystrophy?

Answer 28

• Genetic testing (definitive)
• Creatinine kinase
• Muscle biopsy