Do You Have Charcot-Marie-Tooth Type 4 (CMT4)? We Need Your Help
Autosomal recessive demyelinating CMT4 patients present with earlyonset and slowly progressing symptoms. These include progressive distally accentuated weakness and atrophy of muscles in the lower limbs. In addition, patients may have weakness and atrophy of hands, sensory loss and pes cavus (high-arched feet), and walking difficulties. Further information on CMT4 can be found at Orphanet.
Autosomal recessive demyelinating CMT type 4 (CMT4) typically presents with early onset and slowly progressing symptoms. These include progressive weakness and muscle wasting that is most pronounced in the lower limbs (distally accentuated). Patients may also experience weakness and wasting of the hands, sensory loss, pes cavus (high-arched feet, one of the most common signs of CMT), and walking difficulties. Further information on CMT4 is available from Orphanet.
Many genes and their mutations are associated with CMT4, including GDAP1, MTMR2, SBF2, SH3TC2, NDRG1, EGR2, PRX, FGD4, and FIG4. Each of these genes plays a different role. For example, GDAP1, the most frequent genetic cause of CMT4, encodes a protein on the outer mitochondrial membrane that helps regulate the mitochondrial network. MTMR2 encodes a protein that may have a role in neural membrane recycling and trafficking. A more recently identified mutation in SURF1 encodes cytochrome c oxidase, a protein anchored to the mitochondrial inner membrane. Some genes, such as MTMR2 and FIG4, interact to control the phospholipid substrate PtdIns(3,5)P2 in neurons and Schwann cells, regulating phospholipid metabolism.
Understanding the full complexity of mutations across one or more of these genes, and predicting the resulting symptoms, remains difficult because these genes regulate proteins with many different functions. Significant gaps in understanding this disease remain, and as of the time of this post there is no approved treatment for CMT4. The prevalence is also unknown.
We would like to evaluate potential early-stage therapeutic treatments for CMT4, and you can help. If you have CMT4, please register with the Global Registry for Inherited Neuropathies (GRIN). Your participation can help establish a prevalence estimate and may open doors to future research opportunities.