Hereditary motor and sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth disease, is the most common inherited neuromuscular disorder. It is characterized by slowly progressive distal weakness and muscle atrophy in the legs and later in the hands. There are two major types - one with slow nerve conduction velocities associated with demyelinating neuropathy, and one with relatively normal nerve conduction velocities associated with axonal degeneration. Most families demonstrate autosomal dominant inheritance with a 50% chance of offspring being affected if a parent has the disease.

1. (HMSN)
Charcot – Marie Tooth

2. Hereditary Disorders
Hereditary Motor and Sensory Neuropathy (HMSN)
: Aka Charcot – Marie Tooth (CMT)
: linked to specific chromosomal abnormalities
:most common inherited neuromuscular disorder.

3. Hereditary Motor and Sensory
Neuropathy (HMSN)
 Slowly progressive distal weakness
 Muscle atrophy
 Sensory loss
:was first described by Charcot and Marie in France &
independently by Tooth in England.

4. 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

5. 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

7.  In 1975, the disease was classified further by Dyck into
seven distinct diseases:
HMSN Type Characteristics
1a 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.

8. 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.

9. HSMN
Etiology
 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

10. HSMN
Epidemiology
 A 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.

11. HSMN
 Thomas and colleagues found that 75% of patients
with CMT1A developed clinical evidence of disease
before age 10, and 85% before age 20.

12. HSMN
Clinical Manifestations
 The phenotypes of the different CMT subtypes are
relatively similar.
 Motor symptoms predominate over sensory symptoms
in all age groups.

13. HSMN
Clinical Manifestations
 Early Onset (Infant)
delay in motor milestones
a gait or running impairment (toe walking)
 Adolescents
steppage gait, ankle injuries, or deformities like pes
cavus or thin lower legs

14. HSMN
Clinical Manifestations
 Gait 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.