Charcot-Marie Tooth disease (CMT) may be the most common inherited disorder of the peripheral nervous system, but that only puts the official patient count in Denmark at about 22.5 cases per 100,000 people. However, researchers at Denmark’s Aarhus University wondered whether that number was low. As a heterogeneous disorder, Charcot-Marie Tooth disease can arise for a wide variety of reasons in different patients, which makes diagnosis difficult.

In the study, “A Search for Undiagnosed Charcot-Marie-Tooth Disease Among Patients Registered with Unspecified Polyneuropathy in the Danish National Patient Registry,” published in the journal Clinical Epidemiology, researchers went back in time, and applied CMT diagnostic criteria to the records of the full collection of the Danish National Patients Registry over 40 years, re-evaluating patients who had essentially gone undiagnosed, sent home with the incomplete diagnosis ‘unspecified polyneuropathy’, or unexplained nerve damage to the skin, muscles, or any other organs. The retroactive search found that the rate of CMT could be 16% higher than previously reported.

Charcot-Marie Tooth disease (CMT)  is a rare neurological disorder that interferes with motor and sensory nerves, disrupting a person’s peripheral nerves from properly communicating sensory information to the muscles.

Symptoms usually begin during adolescence or early adulthood, when over time, patients begin to notice weakness in their feet and lower leg muscles, foot deformities such as unusually high arches or hammertoes, weakness and muscle atrophy in the hands, and deformities as a result of muscles loss, which eventually impede fine motor skills and walking. While no cure exists, there are physical and occupational therapies, orthopedic devices, pain-killers, and surgery to treat symptoms.

Albeit rare, CMT clocks in among the most common neurological disorders with current estimates at around 22.5 cases per 100,000 in Denmark.  However, the true prevalence is still unfounded, with enormous variations in reported numbers.

This is because the rare disorder can be triggered by an array of mutations on the genes involved in communicating sensory information from the brain to the muscles, causing the number of potential triggers to be a wide and ever growing number. This means some patients that might have atypical symptoms, mild symptoms, or without the full cast of symptoms often go undiagnosed.

This led researchers to suspect the number of recorded cases was too low.

The researchers set out to find the patients whose specific cause of  nerve damage remained inconclusive. Combing through the Danish National Patients Registry (DNPR) They considered any Danish patients under age 40 who were diagnosed with ‘unspecified polyneuropathy’ between 1977 and 2012.

Of the 31,422 patients identified with a diagnosis of UP,  516 had additionally already received a CMT diagnosis. Amongst the remaining 30,903 people, they identified an additional 940 patients who could potentially be reclassified, matching the CMT criteria of one diagnosis of UP before turning 40, without any related diagnosis involved alcohol, diabetes, or neuropathy.

From this group of potentials, the researchers randomly selected 20 patients at five year intervals for more thorough analysis. Of the 79 patients who had complete records, they found an additional 200 patients or 21.5% of the sample who passed further scrutiny for CMT criteria. This approximation led the doctors to conclude the true prevalence could be more like their studies adjusted rate of 26.1 CMT cases per 100,000 people, a 16% increase in suspected cases.