CHARCOT-MARIE-TOOTH DISEASE

PRESENTEDBY

DR. SAJIDA KHALIDPGR (FCPS-II TRAINEE)

DEPARTMENT OF PEDIATRICS

SHEIKH ZAYED MEDICAL COLLEGE RAHIM YAR KHAN

A 14 years old girl presented with complaints of: Progressive weakness of legs, Progressive deformities of feet & hands, since

the age of 4 years. ON EXAMINATION:

Claw hand Foot drop and pes cavus deformity Deep tender reflexes – absent Fine touch sensation diminished at lower

extremity.

Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease; HMSN Type I)

Genetically and clinically heterogeneous group of inherited disorders of the peripheral nervous system characterised by progressive loss of muscle tissue and touch sensation across various parts of the body.

PREVALENCE

3.8/100,000. It is transmitted as an autosomal

dominant trait with 83% expressivity; the 17p11.2 locus is the site of the abnormal gene.

Autosomal recessive. X-Linked HMSN type I.

Causes

Charcot–Marie–Tooth disease is caused by mutations that cause defects in neuronal proteins. Nerve signals are conducted by an axon with a myelin sheath wrapped around it. Most mutations in CMT affect the myelin sheath, but some affect the axon.

The most common cause of CMT (70-80% of the cases) is the duplication of a large region in chromosome 17p12 that includes the gene  PMP22. Some mutations affect the gene MFN2for a mitochondrial protein.

Neurons, Schwann cells, and fibroblasts work together to create a working nerve. Schwann cells and neurons exchange molecular signals that regulate survival and differentiation. These signals are disrupted in CMT.

Demyelinating Schwann cells causes abnormal axon structure and function. They may cause axon degeneration, or they may simply cause axons to malfunction.

The myelin sheath allows nerve cells to conduct signals faster. When the myelin sheath is damaged, nerve signals are slower, and this can be measured by a common neurological test,electromyography. When the axon is damaged, on the other hand, this results in a reduced compound muscle action potential.

Classification

CMT is a result of genetic mutations in a number of genes. Based on the affected gene, CMT can be categorized into types and subtypes.

CMT1 Demyelinating type 30% Causes severe demyelination, thereby impairing nerve conduction velocity.

CMT2 Axonal type 20–40%. Mainly affects axons. Tends to affect lower extremities more than upper extremities. Clinical symptoms are often less severe than in CMT1. As it is an axonopathy, average nerve conduction velocity is usually not affected.

CLINICAL MANIFESTATIONS Most patients are asymptomatic until late

childhood or early adolescence, but young children sometimes manifest gait disturbance as early as the 2nd yr.

Children with the disorder are often described as being clumsy, falling easily, or tripping over their own feet.

The onset of symptoms may be delayed until after the 5th decade.

Muscles of the anterior compartment of the lower legs become wasted, and the legs have a characteristic stork-like contour.

The muscular atrophy is accompanied by progressive weakness of dorsiflexion of the ankle and eventual footdrop.

The process is bilateral but may be slightly asymmetric.

Pes cavus deformities invariably develop due to denervation of intrinsic foot muscles, further destabilizing the gait.

Atrophy of muscles of the forearms and hands is usually not as severe as that of the lower extremities, but in advanced cases contractures of the wrists and fingers produce a claw hand.

Proximal muscle weakness is a late manifestation and is usually mild.

Axial muscles are not involved

Autonomic manifestations may be expressed as poor vasomotor control with pallor of the skin of the feet and inappropriately cold feet.

Sensory involvement mainly affects large myelinated nerve fibers that convey proprioceptive information and vibratory sense, but the threshold for pain and temperature may also increase.

Some children complain of tingling or burning sensations of the feet, but pain is rare. Because the muscle mass is reduced, the nerves are more vulnerable to trauma or compression.

Nerves often become palpably enlarged. Tendon stretch reflexes are lost distally. Cranial nerves are not affected. Sphincter control remains well preserved.

Autonomic neuropathy does not affect the heart, gastrointestinal tract, or bladder. Intelligence is normal.

A unique point mutation in PMP22 causes progressive auditory nerve deafness in addition, but this is usually later in onset than the peripheral neuropathy.

LABORATORY FINDINGS AND DIAGNOSIS

Motor and sensory nerve conduction Electromyography (EMG) and muscle

biopsy. Nerve biopsy is diagnostic. The definitive molecular genetic diagnosis

may be made in blood

TREATMENT

Stabilization of the ankles is a primary concern. In early stages.

Stiff boot Lightweight plastic splints External short-leg braces may be required when

footdrop becomes complete. Surgical fusion of the ankle may be considered in

some cases.

The leg should be protected from traumatic injury.

In advanced cases, compression neuropathy during sleep may be prevented by placing soft pillows beneath or between the lower legs.

Burning paresthesias of the feet are not common but are often abolished by phenytoin or carbamazepine.

No medical treatment is available to arrest or slow the progression.