About Charcot-Marie Tooth

Charcot-Marie-Tooth disease/syndrome or CMT is named after the three neurologists who first described the condition in 1886 ( Charcot, Marie and Tooth) It is the most common inherited neuromuscular disorder, affecting approximately 1 in 2,500 individuals. The other term commonly used to describe the condition is hereditary motor and sensory neuropathy (HMSN). This name describes the two primary features of this condition: it is hereditary (passed on in the genes from parent to child) and it affects the motor and sensory peripheral nerves.

CMT is not in fact a single disorder but a group of conditions that have some similarities. Neuropathy means a disease of the peripheral nerves. These are the nerves that connect the spinal cord to the muscles, joints and skin and carry messages in both directions, and in CMT they do not function normally. The group of conditions known as CMT cause weakness and wasting of the muscles below the knees and often those of the hands as well. Many affected individuals also have loss of feeling in the hands and feet. Disease onset usually occurs during the first decades of life and gets worse slowly. Severity is highly variable even within families.
 
Because there are many different types of CMT, it is important to determine exactly which type someone has. Although in the last decade many genes responsible for CMT have been identified, not all of the genes that cause the condition have yet been found. This means that nerve conduction studies (electrical tests on the nerves) are still often used to help make the diagnosis. A DNA test for the most common form of CMT (type 1A) might be performed first if there is a clear family history of autosomal dominant inheritance of the condition.

Presentation of CMT

Onset is slowly progressive.

CMT1

This is the most common form. Onset is usually by the age of 10 years with:

• Muscle weakness and wasting starting from the intrinsic muscles of the feet, and gradually affecting the lower leg and lower thigh. The pattern of distal wasting in the legs is sometimes described as 'inverted champagne bottles'. Hands and forearms may also be involved. Wasting of the small muscles of the hands causes finger curling and difficulty in straightening or abducting them.
• Sensory loss follows the same pattern, beginning in the distal legs and arms with decreased sensation of vibration and touch. Proprioceptive sensory loss can cause sensory ataxia and a steppage gait. Tasks involving fine motor control of the hands may also become progressively more difficult. .
• Generalised tendon areflexia.
• There may be foot drop and foot deformity. Pes cavus (high arch) has a 25% occurrence rate in the first decade of life and a 67% occurrence rate in later decades. Hammer toes and pes planus (flat feet) are also seen. Patients may experience difficulty walking or running, often tripping. Pressure palsies are common.
• Spinal deformities, eg thoracic scoliosis, occur in 37-50% of patients with CMT1.
• Other common symptoms and signs include hand tremors and muscle cramps.

CMT2

Primary peripheral axonal neuropathy (CMT2 or HMSN-II) with onset usually in the second decade, but may not appear until later. The pattern of peripheral weakness and wasting is similar to CMT1.

CMT3

This is characterised by infantile onset, usually by 2 years. Onset can occur by the time of birth, presenting with hypotonia or floppy baby syndrome. It results in severe demyelination with delayed motor skills and is much more severe than type 1.

CMTX

CMTX1 is usually mild in women but in men there is moderate to severe peripheral neuropathy. With other CMTX forms, only men are affected. For CMTX1 there is usually subclinical central nervous system involvement (eg mild clinical signs, MRI cerebral white matter abnormalities, and EEG abnormalities).

For more information on CMT - www.cmt.org.uk