Clinical Aspects of CMT Flashcards
What is Charcot-Marie-Tooth disease also known as?
- Also known as Hereditary Motor and Sensory Neuropathy and Peroneal Muscular Atrophy.
What is the prevalence of CMT?
The prevalence of CMT is 1 in 3,300.
What is CMT caused by clinically?
CMT is caused by disruption of the relationship between the myelin sheath and the axon.
What are disorders causing demyelination generally classified as?
Disorders causing demyelination are generally classified as HSMN1.
What are disorders causing axonal problems generally classified as?
Disorders causing axonal problems are generally classified as HSMN2.
What characteristics result in classification of HSMN1 or HSMN2?
- Disorders causing demyelination are generally classified as HSMN1.
- Disorders causing axonal problems are generally classified as HSMN2.
- Some mutations affect this relationship more severely than others and can lead to a myelin gene giving you HSMN2 so there is some crossover between type 1 and type 2.
Describe the clinical features of Charcot-Marie-Tooth disease.
- Usually presents between 5-15 years but is not usual to have a history of clumsiness or toe walking before this.
- May present with frequent trips/falls dies to foot drop, a high instep or curled toes.
- Over time there is loss of muscle bulk in the lower calves (“inverted champagne bottle”) and high arched feet (pes cavus).
- loss of sensation in hands and feet.
- Weakness of hands, usually not until adult life.
- Nerves to the feet are longest in the body so you are going to notice problems first. Nerves to the hands are shorter so you don’t notice the slowing of the nerve conduction so much.
- Patients may complain of not being able to walk on uneven ground, problems with ripping of bottle tops, problems getting shoes that fit, problems wearing high heels.
Chat is the classical foot shape in CMT disease?
- Patients develop a high arch to the foot over time and curling of their toes - have a very high instep that doesn’t fit into standard shoes. This is why they have trouble finding shoes that fit.
Charcot-Marie-Tooth disease may be classified in a number of different ways - explain the more common classification systems.
- There are classifications based on clinical presentation and neurophysiology or molecular genetics but there is no consensus.
- One of the more common ways that people think about HSMN is based on pathology.
- CMT1 involves abnormal myelin. It displays AD inheritance and makes up about 40-50% of CMT.
- CMT2 involves axonopathy. It is also inherited in an AD fashion and makes up 10-15% of all CMT.
- There is an intermediate form of CMT that involves a combination of myelinopathy and axonopathy. This form is inherited in an AR fashion and is rare.
- CMT4 involves either myelinopathy or axonopathy. The inheritance pattern is AR and it is rare.
- CMTX involves axonopathy with secondary myelin changes. They inheritance of CMTX is X-linked and it makes up about 10-15% of all CMT.
Briefly outline the different types of CMT.
- CMT1 involves abnormal myelin. It displays AD inheritance and makes up about 40-50% of CMT.
- CMT2 involves axonopathy. It is also inherited in an AD fashion and makes up 10-15% of all CMT.
- There is an intermediate form of CMT that involves a combination of myelinopathy and axonopathy. This form is inherited in an AR fashion and is rare.
- CMT4 involves either myelinopathy or axonopathy. The inheritance pattern is AR and it is rare.
- CMTX involves axonopathy with secondary myelin changes. They inheritance of CMTX is X-linked and it makes up about 10-15% of all CMT.
Outline the clinical features of CMT1.
CMT1:
- Demyelinating, slow nerve conduction of 5-30m/sec (normal >40-45m/sec).
- Distal muscle weakness, sensory loss, <5% become wheelchair dependant.
- 70-80% of CMT1 is due to PMP22 duplications.
Outline the clinical features of CMT2:
CMT2:
- Axonal, nerve conduction usually in normal range but may be normal or mildly abnormal.
- Similar problems to CMT1 but less disabled.
Outline the clinical features of the intermediate form of CMT.
Intermediate form:
- Typical HMSN phenotype but clinical and pathological evidence of abnormal myelin and axonopathy.
- Motor nerve conduction velocities range from 25-50m/sec and so there is an overlap with those seen in CMT1 and 2.
Outline the clinical features of CMT4.
CMT4:
- Group of progressive motor and sensory axonal and demyelinating neuropathies.
- Distinguished by being AR.
Outline the clinical features of CMTX1.
CMTX1:
- Moderate to severe motor and sensory neuropathy in affected males with mild to no symptoms in females.
- Deafness and central nervous system symptoms in some.
- Unless you can see the absence or presence of male to male transmission it can be difficult to distinguish between x-linked forms and other forms of CMT.
- The other x-linked forms can be associated with intellectual disability, optic neuropathy, spasticity or pyramidal signs.
