BY BRUCE HARRIS-LANGLOIS – originally published in the Summer 2022 CMTA Report.

Each of us has our own CMT story. Mine started at the age of 54 when I was walking in my neighborhood and it suddenly struck me that my gait—a high step followed by a slap on the ground and swinging my foot somewhat to the outside—was exactly like my mother’s. Later I began to notice the aching in my legs, the sprained ankles, the numbness and tingling in my feet, my very high arches and the odd wear pattern on the soles of my shoes.

“I have CMT,” I told my doctor in 2001.

“What’s that?” he asked.

“It’s genetic, but I don’t know the name of the gene,” I replied.

When my mother was a young woman, my grandmother told her that her feet looked like those of my great-grandfather, a carpenter and joiner who lived from 1828 to 1893. People called him a “cripple.” In 1871, his daughter wrote in a letter to one of her nine siblings, “[F]ather falls every day…he grew old very fast.”

About that time, my great-grandfather wrote he could no longer do his job. “I have not been able to do any work for five years. I have not dressed nor undressed in over three years without someone to help me [sic] my hands and arms are drawn out of shape [sic] that I cannot feed myself.… Some days I can walk around considerable, again I could not turn round to save my life for two or three weeks.”

As a child in the 1950s, I remember my grandmother being feeble, walking with a cane and wearing funny-looking shoes. As my mother reached middle age, she stumbled and fell a lot and her hands got gnarly and painful. She thought her symptoms were a holdover from suspected polio as a teenager. My mother was clinically diagnosed with CMT Type 2 in 1993 before genetic testing was well developed for Type 2 subtypes. Even now fewer than 50 percent of people with Type 2 know their subtype, a problem the CMTA is working on solving. It seemed to me like an unbroken autosomal dominant genetic line from my great-grandfather to my grandmother to my mother to me. But I wanted it confirmed by a clinical diagnosis plus genetic testing.

I had taken several genetic tests at Dr. Michael Shy’s CMT Clinic at Wayne State University in Detroit, but my gene had not yet been discovered. Then, in 2017, Dr. Richard Lewis at the CMT Clinic at Cedars-Sinai in Los Angeles submitted a blood sample to GeneDx for testing, which identified a variant on the MME gene. This was the likely cause of autosomal dominant CMT Type 2T, characterized by late-onset axonal CMT, usually starting around age 50. Finally, I knew—2T.

Four generations of my family have had CMT symptoms consistent with the MME gene and Type 2T. In a few decades, we progressed from anecdotes in family letters to discovering a new subtype, thanks in part to the CMTA’s Strategy to Accelerate Research (STAR).

Could our genealogy tell us even more? My mother had researched genealogy for her and my father’s families for years, but she wasn’t looking for hereditary diseases. While autosomal dominant and recessive inheritance patterns remain something of a mystery to me, I wondered if I could understand them better through the lineage of grandparents, aunts, uncles and cousins.

My mother’s ancestors were northern Europeans, with names like Harris, Bronson and Burke. But my father’s family was almost entirely French, with names like Langlois, LaFlamme and Doucet. My grandmother was a Langlois, born in 1888. Her father was French Canadian, born in 1843, and his parents were born in 1798 and 1805, all in Quebec. Another generation back, her parents Daniel and Marguerite were second cousins once removed, third cousins once removed, half third cousins, fourth cousins once removed, half fifth cousins and half sixth cousins—more complicated than an L.A. freeway interchange.

These people are known as the Acadians. In the 1600s, Acadia was located in what is now New Brunswick, Nova Scotia and Prince Edward Island. Around 1755 many Acadians were forced to move to England, France, Quebec and the American colonies, in particular Louisiana. (The word Cajun is derived from Acadian.) Acadians were a closely knit people and kept to themselves in small communities, which led to a higher than normal frequency of genetic disorders. CMT is one of the so-called Acadian diseases. I wondered if my genealogy could help explain where my CMT came from.

At the CMT Clinic at Cedars-Sinai, I met with Licensed Certified Genetic Counselor Tara Jones, MS. I asked whether I could have inherited a recessive genetic form of CMT from my father’s side in addition to the autosomal dominant MME gene from my mother’s side. Finding out if I am a carrier of the recessive gene would be valuable knowledge for my children and grandchildren, especially since my children are approaching 50, the age when my mother and I were noticeably affected by CMT. The genetic pattern would give my children a starting point in diagnosing any infirmities that suggest CMT.

Tara Jones advised me that the likelihood of having a recessive Acadian gene was slight for three reasons. First, the fact that CMT is seen more often in the Acadian genetic line does not mean that all Acadian descendants have CMT.

Second, I am not aware of any French-Canadian grandparents, great-grandparents, aunts, uncles or cousins, who experienced CMT symptoms. We don’t know or suspect that any of them had CMT, and neither of my two living cousins on that side can recall any foot, gait, walking, tripping or falling issues in their families.

Finally, though MME can cause CMT with both autosomal dominant and autosomal recessive inheritance patterns, Tara confirmed that my specific genetic change has only been reported to have autosomal dominant inheritance, which follows my maternal lineage of a relative with CMT in every generation.

My gene is MME, the genetics are still beyond my comprehension and my genealogy is a road map in the rearview mirror. I will keep going to the CMT Clinic at Cedars-Sinai because the best chance for a world without CMT is more STAR-funded research, more clinical trials, more CMTA patient and family support, more patients going to the CMTA’s four dozen Centers of Excellence and more genetic testing and interpretation. Looking forward to the road ahead, I want CMT to stop with me.