Pediatric Inherited Peripheral Neuropathies

Question 1

What is the most heritable peripheral neuropathy?

Answer 1

Charcot-Marie-Tooth (CMT), or hereditary motor and sensory neuropathies (HMSNs)

Question 2

Classic presentation of CMT?

Answer 2

progressive motor and sensory nerve impairment with onset in the 1st or second decade of life

• insidious progressive muscle weakness - distal strength affected more than proximal
• atrophy of hand intrinsic muscles
• Pes cavus deformity
• stocking glove distribution sensory loss

Question 3

Inheritance pattern of CMT1?

Answer 3

Autosomal dominant transmission

Question 4

Is CMT1 demyelinating or axonal?

Answer 4

Demyelinating

Question 5

Early predilection for weakness and atrophy of the anterior compartment peroneal-supplied muscles is associated with which variant of CMT?

Answer 5

CMT1

Question 6

Which gene is associated w/ CMT1A?

Answer 6

PMP-22

Question 7

CMT1A accounts for which percentage of CMT cases?

Answer 7

80%

Question 8

What is the inheritance pattern for CMT2?

Answer 8

Autosomal dominant AND autosomal recessive inheritance

Question 9

Is CMT2 demyelinating or axonal?

Answer 9

axonal pathology

Question 10

What characteristics can differentiate CMT2 from CMT1?

Answer 10

variable onset and demonstrates a greater degree of lower extremity weakness than CMT1

Additional subtypes can include
- optic atrophy
- pyramidal tract involvement
- vocal cord paresis
- hearing impairment
- Adie pupils (tonic pupil, parasympathetic denervation)
- diaphragm involvement

Question 11

What is Dejerine-Sottas disease?

Answer 11

Previously classified as CMT3, now considered to be a clinical continuum between CMT1 and congential hypomyelinating neuropathy (congenital hypomyelinating neuropathy that presents with severe weakness at birth or within the first month of life)

Autosomal dominant and autosomal recessive inheritance patterns

Question 12

What is the inheritance pattern of CMT4?

Answer 12

Autosomal recessive inheritance

Question 13

Is CMT4 primary demyelinating or axonal?

Answer 13

Demyelinating

Question 14

What characterizes CMT4?

Answer 14

Severe childhood onset weakness and sensory changes

Subtypes can include:
- severe motor delays
- vocal cord paralysis
- glaucoma

Question 15

What is the second most common type os demyelinating CMT?

Answer 15

X-linked CMT

Both dominantly and recessively inherited X-linked conditions exist

Question 16

Unique clinical features of X-linked CMT?

Answer 16

similar to CMT1, but men tend to present with more severe disease than women

• cases of associated CNS white matter abnormalities that manifest with ataxia or cognitive abnormalities have been reported

Question 17

Hereditary neuropathy with pressure palsy (HNPP) is associated with what genetic abnormality?

Answer 17

Reciprocal deletion of PMP-22 gene (CMT1A is associated with duplications in PMP-22)