New LITAF Gene Mutation, Unusual CMT1C Symptoms Reported in Case

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by Vanda Pinto PhD |

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case report describes uncommon CMT1C features and new mutation/Charcot-Marie-Tooth News/doctor-patient consultation illustration

A European man was finally diagnosed with a rare mutation causing Charcot-Marie-Tooth disease type 1C (CMT1C), although his initial symptoms, including weakness of only one arm, were considered uncharacteristic of this disorder, a case report described.

The study, “Atypical presentation of Charcot-Marie-Tooth disease type 1C with a new mutation: a case report,” was published in the journal BMC Neurology.

CMT1C is a rare subtype of CMT1 that is caused by mutations in the LITAF gene. Because mutations in this gene are so rare, studies clinically describing affected patients are very limited.

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According to the few existing cases, CMT1C is associated with loss of myelin — the fat-rich layer covering the nerve extensions that transmit nerve signals — and often with a muscular weakness that makes it difficult to lift the front part of the foot and toes, as well as foot drop. That foot condition, known as pes cavus, is a deformity characterized by a high arch that does not flatten with weight-bearing.

Patients with CMT1C may show typical CMT1A symptoms, or have impaired sensation with a burning or prickling feeling called paresthesias. However, symptoms may vary even among family members with the same mutation.

In this study, researchers in the Slovak Republic described the case of a 56-year-old man with an unusual presentation of CMT1C.

Despite being previously healthy and active, the man developed paresthesias and weakness and cramps on the right arm, over about three months. His muscle strength was assessed using the Medical Research Council’s scale (MRC scale) of muscle power, which runs from 0 (no contraction) to 5 (normal). While his right arm received a score of MRC3, his left arm showed normal strength with a score of MRC5. The patient also had pes cavus with normal muscle strength, low reflex response in muscles, and reduced vibration sense in the legs.

Within the following six months, his muscle weakness worsened in the right arm and hand. The patient also began experiencing weakness and paresthesias in his left arm. Daily tasks which required fine motor control, such as buttoning clothes, unscrewing bottle caps, and turning doorknobs, became difficult. However, muscle strength in his legs was normal.

Next, the researchers carried out nerve conduction studies to evaluate the damage to the man’s peripheral nerves. The patient showed reduced nerve conduction velocities. Moderate nerve damage, or neuropathy, was found in the arms, and severe nerve damage in the legs. Both the sensory nerves, which provide feeling, and the motor nerves — responsible for movement — were affected.

Electromyography, which is used to determine muscle response or electrical activity in response to a nerve’s stimulation, showed loss of nerve supply in the arm muscles.

Further investigations included laboratory tests that showed normal results, and negative genetic testing for CMT1A and hereditary neuropathy with pressure palsies.

Together, these results led the man’s healthcare providers to make a diagnosis of multifocal acquired demyelinating sensory and motor neuropathy (MADSAM).

After no success with corticosteroids, clinicians tried an antibody therapy that delivered directly into a vein (IVIG). That therapy also failed to stop the patient’s weakness progression, although given frequently and in a high dose for two years.

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After collecting information on the clinical history of the patient’s family members, the healthcare team found that his 79-year-old mother and 31-year-old son both showed signs of nerve damage. Although neither complained of having arm or leg symptoms, both had pes cavus, lack of reflexes, and decreased vibratory sensations in the legs. Accordingly, nerve conduction studies revealed moderate nerve damage in the arms and severe nerve damage in the legs caused by loss of myelin.

Genetic tests showed that the patient, as well as his mother and son, had a previously unreported mutation in one of the copies of the LITAF gene. This mutation was dominant, meaning that one copy of the variation is enough to cause the disease, and was predicted to be disease-causing by different softwares.

“The presentation of the CMT1C [features] in our patient was unusual compared to patients with identical diagnoses in previous studies,” the investigators wrote.

“CMT1C should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating [myelin loss] neuropathy,” they concluded.