Stroke-like symptoms and mild cognitive impairment are among non-specific symptoms that may suggest X-linked Charcot-Marie-Tooth type 1 (CMTX1), a case series shows.
The series, “GJB1 Mutation-A Disease Spectrum: Report of Case Series,” was published in the journal Frontiers in Neurology.
CMTX1, also called X-linked CMT, is caused by mutations in the GJB1 gene, located on the X chromosome, which provides instructions for making a protein called connexin 32 (Cx32). Cx32 is primarily found in a type of glia cells — nerve cells that nourish, protect, and support neurons — known as Schwann cells.
Schwann cells produce myelin, a fatty substance that wraps around nerve fibers and serves to increase the speed of electrical communication between neurons.
When mutations impair the normal function of GJB1, myelin production is affected, compromising the communication between neurons and leading to progressive sensorimotor neuropathy (loss of sensation or the ability to move due to nerve damage).
However, children and young adults with CMTX1 rarely experience temporary symptoms affecting the central nervous system (CNS), which consists of the brain and spinal cord.
Researchers in China described the cases of 11 CMTX1 patients — one female and 10 males, ages 7-34, from nine families — carrying GJB1 mutations and showing distinct sets of neurological symptoms.
Eight different GJB1 mutations were identified, including one that had never been described. Most patients had a family history of the disease and started experiencing the first symptoms of CMTX1 during childhood.
Nine patients had only peripheral neuropathy, the most common signs of which were weak lower legs and high-arched feet.
Investigators zeroed in on two patients who showed signs of central nervous system involvement. One of them, dubbed Patient 1, had both peripheral neuropathy and mild cognitive impairment, while the other, Patient 11, had recurrent episodes of limb weakness and difficulty using and understanding words (aphasia).
Patient 1 was 33-year-old man who had had high-arched feet since childhood and complained of foot numbness for two years. He couldn’t extend his feet or toes.
“His maternal grandfather, two aunts, two cousins, and elder brother had similar symptoms of feet weakness and high-arched feet, and his mother had high-arched feet,” the researchers said.
Neurological examination showed that none of his limbs responded to stimuli (areflexia). He had mild muscular weakness and atrophy (shrinkage) in his hands, moderate muscular atrophy in his lower legs, and he was unable to lift his feet while walking due to muscle weakness.
Despite not having any cognition-related complaints, tests revealed he had mild cognitive impairments. Nerve conduction studies also indicated he had demyelinating (loss of myelin) polyneuropathy involving both motor and sensory nerves.
Patient 11 was a 7-year-old boy who over the previous 16 months had experienced recurrent episodes resembling the classic symptoms of stroke.
“During dinner, he suddenly had weakness of all four extremities and couldn’t hold the spoon, and had difficulty in speaking,” the researchers wrote. “There was no alteration of consciousness. The symptoms resolved two to three minutes later, but recurred … two times in similar fashion in the following two days,” the researchers said.
Six months after these attacks, he had three others in which he experienced weakness on the right side of his body and difficulty speaking. Imaging and laboratory findings were normal, except for the presence of immunoglobulin bands in serum and cerebrospinal fluid (liquid that circulates in the brain and spinal cord), indicative of a neurological or blood disorder.
“The case of patient 11 reminds us that GJB1 mutations should be a consideration in the differential diagnosis of recurrent reversible stroke-like CNS deficits in children, even without evidence of peripheral neuropathy,” the researchers said.
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