Hereditary Motor and Sensory Neuropathy

(HMSN)Charcot – Marie Tooth

Hereditary DisordersHereditary Motor and Sensory Neuropathy

(HMSN)

: Aka Charcot – Marie Tooth (CMT): linked to specific chromosomal abnormalities:most common inherited neuromuscular disorder.

Hereditary Motor and Sensory Neuropathy (HMSN)Slowly progressive distal weaknessMuscle atrophySensory loss 

:was first described by Charcot and Marie in France & independently by Tooth in England.

Hereditary Motor and Sensory Neuropathy (HMSN) 2 MAJOR GROUPS

Group 1:  was characterized by slow nerve conduction velocities and evidence of hypertrophic demyelinating neuropathy.

Group 2 :was characterized by relatively normal nerve conduction velocities and axonal degeneration

Hereditary Motor and Sensory Neuropathy (HMSN)

Most of the families demonstrated autosomal dominant inheritance.

 If a parent has the disease the offspring have a 50% chance of also having the disease

In 1975, the disease was classified further by Dyck into seven distinct diseases:

HMSN Type Characteristics1a and 1b( Most Common Type)

Dominantly inherited hypertrophic

demyelinating neuropathies

Individuals experience weakness and atrophy in

the lower legs in adolescence, and later

develop weakness in the hands

Type 2 Dominantly inherited Neuronal Neuropathies

Onset in Adolescence, Sx similar to Type 1.

Type 3“Dejerine – Sottas”

Hypertrophic Neuropathy of Infancy

Onset in Infancy & results in delayed motor skills, much more severe than

Types 1 & 2 Type 4 hypertrophic neuropathy

associated with phytanic acid excess

Muscle weakness and atrophy as in other types of CMT, but set apart by

being autosomal recessive inheritance.

Type 5 associated with spastic paraplegia

Onset between ages 5–12. Lower legs are affected first by muscle weakness and atrophy followed by the upper extremities. Type 5 is also associated with visual and hearing loss

Type 6 with optic atrophy Early onset muscular weakness and atrophy followed by optic atrophy resulting in vision loss and possibly blindness.

 type 7 with retinitis pigmentosa

Later onset with muscular weakness and atrophy mostly in the lower extremities.

HSMNEtiology Chromosomes 17 and 1 seem to be the most

common chromosomes with mutations.There is also evidence that the disease could

be X-linked.Most often relatives with the disease

manifest the same type of the disease

HSMNEpidemiologyA worldwide meta-analysis estimated a

prevalence of 1 per 10,000 individuals, and a prevalence of 10.8 per 100,000 was found in western Japan.

Affects males earlier, more frequently, and more severely than females.

Onset is usually in childhood.

HSMNThomas and colleagues found that 75% of

patients with CMT1A developed clinical evidence of disease before age 10, and 85% before age 20.

HSMNClinical Manifestations The phenotypes of the different CMT

subtypes are relatively similar.

Motor symptoms predominate over sensory symptoms in all age groups.

HSMN Clinical Manifestations

Early Onset (Infant)delay in motor milestonesa gait or running impairment (toe walking)Adolescentssteppage gait, ankle injuries, or deformities like pes cavus or thin lower legs

HSMN Clinical ManifestationsGait is impaired by distal weakness but

usually remains independent; proximal weakness only affects a minority of patients.

clinical progression is slow and any acceleration should lead to a workup for superimposed conditions.