EMERGENCY:CMT patients must avoid neurotoxic medications — vincristine, paclitaxel/taxanes, cisplatin, high-dose vitamin B6 (>200 mg/day), amiodarone, linezolid, nitrofurantoin, and isoniazid without pyridoxine. Always disclose your CMT diagnosis to every treating physician and pharmacist. —call040-46324365immediately — 24 hours, 7 days— 24/7
Charcot-Marie-Tooth Disease (Hereditary Motor Sensory Neuropathy) in Hyderabad — KIMS Neuroscience
Charcot-Marie-Tooth disease (CMT), also called hereditary motor and sensory neuropathy (HMSN), is the most common inherited disorder of the peripheral nervous system. It affects approximately 1 in 2,500 people globally — making it more common than many well-known neurological conditions. In India, CMT is frequently underdiagnosed or misdiagnosed as cerebral palsy, muscular dystrophy, or "weak legs since childhood" until a genetic test confirms the diagnosis.
About This Condition
Charcot-Marie-Tooth Disease at a Glance
The essential facts that shape how CMT is recognised and managed at KIMS — the 1-in-2,500 global prevalence, the predominantly autosomal dominant inheritance, the CMT1A/PMP22 duplication that accounts for half of all cases, the demyelinating vs axonal NCS signatures, the pes-cavus / distal-weakness / absent-ankle-reflex clinical triad, the CMT gene panel pathway, the consanguinity caveat for CMT4 in Telangana/AP, and the AFO + physiotherapy + neurotoxic-drug-avoidance management framework.
Prevalence
1 in 2,500 globally · Most common inherited peripheral neuropathy.
Inheritance
Most CMT1 and CMT2: autosomal dominant (one copy of abnormal gene is enough).
Most common subtype
CMT1A: PMP22 gene duplication on chromosome 17 · Accounts for ~50% of CMT cases.
NCS hallmark of CMT1A
Uniform slowing of motor conduction velocity below 38 m/s in arm nerves (normal >50 m/s).
NCS hallmark of CMT2
Normal or near-normal conduction velocity; reduced CMAP/SNAP amplitudes.
Classic clinical triad
Distal leg weakness + pes cavus (high-arched feet) + absent ankle reflexes.
Onset
CMT1A: childhood/adolescence · CMT2: variable (sometimes adult onset).
Genetic test
CMT gene panel: PMP22 duplication/deletion, MFN2, MPZ, GJB1, GDAP1, others.
Consanguinity note
Autosomal recessive forms (CMT4) more common in consanguineous families in Telangana/AP.
Management
AFO · Physiotherapy · Orthopaedic correction · Genetic counselling · No neurotoxic drugs.
Charcot-Marie-Tooth — The Most Common Inherited Peripheral Neuropathy
Charcot-Marie-Tooth disease (CMT), also called hereditary motor and sensory neuropathy (HMSN), is the most common inherited disorder of the peripheral nervous system. It affects approximately 1 in 2,500 people globally — making it more common than many well-known neurological conditions. In India, CMT is frequently underdiagnosed or misdiagnosed as cerebral palsy, muscular dystrophy, or "weak legs since childhood" until a genetic test confirms the diagnosis.
CMT is not a single disease. It is a family of over 80 genetically distinct conditions, all of which share the feature of progressive damage to the peripheral nerves supplying the limbs. The common clinical thread is: distal leg weakness and wasting (small calf muscles, difficulty lifting the foot), high-arched feet (pes cavus), reduced or absent reflexes in the legs, and a family history of similar symptoms across generations. Some subtypes also affect the hands and, rarely, the respiratory muscles.
Although there is currently no cure for CMT, treatment significantly improves function and quality of life. Ankle-foot orthoses (AFOs) correct foot drop and prevent falls. Physiotherapy maintains strength and flexibility. Orthopaedic surgery addresses severe foot deformity. Genetic counselling guides family planning decisions. At KIMS Hyderabad, CMT diagnosis, genetic testing, and multidisciplinary management are available.
Book a Consultation
Speak directly with the KIMS CMT multidisciplinary team — neurology, clinical neurophysiology (NCS/EMG), clinical genetics (CMT gene panel and counselling), neuropathology (nerve biopsy for selected cases), orthotics (carbon-fibre AFOs), physiotherapy and rehabilitation, paediatrics for childhood-onset cases, and orthopaedic foot & ankle surgery — all coordinated under one roof. No referral required. Monday to Saturday.
040-44885000Genetic counselling available on appointmentTypes of CMT — Major Inheritance Patterns
Three principal CMT categories that determine the diagnostic pathway and family-screening strategy at KIMS — CMT1 (the demyelinating form, with CMT1A/PMP22 duplication accounting for half of all CMT cases), CMT2 (the axonal form, often adult-onset with MFN2 as the commonest gene), and CMTX1 (X-linked, with no male-to-male transmission and intermediate NCS velocities in males).
CMT Type 1 (CMT1) — the demyelinating form
CMT1 is caused by mutations in genes encoding proteins of the peripheral myelin sheath. The most common is CMT1A, caused by a 1.5 Mb duplication of chromosome 17p11.2 containing the PMP22 (peripheral myelin protein 22) gene. Extra copies of PMP22 disrupt myelin formation and maintenance, causing uniformly slowed nerve conduction. CMT1A accounts for approximately 50% of all CMT cases. Other CMT1 subtypes: CMT1B (MPZ mutation — myelin protein zero), CMT1C, CMT1D. All CMT1 subtypes show markedly slowed motor conduction velocity (below 38 m/s in the median nerve at the wrist — normal is above 50 m/s).
CMT Type 2 (CMT2) — the axonal form
CMT2 affects the axon rather than the myelin. Nerve conduction velocity is relatively preserved (above 38 m/s) but the amplitude of the electrical signal (CMAP and SNAP) is reduced, reflecting loss of individual nerve fibres. The most common CMT2 gene is MFN2 (mitofusin 2), which encodes a mitochondrial fusion protein critical for axonal energy supply. CMT2 tends to have adult-onset more often than CMT1A and may be more clinically variable. Some CMT2 subtypes cause vocal cord paralysis (CMT2C) or hearing loss alongside the neuropathy.
X-linked CMT (CMTX1) — no male-to-male transmission
CMTX1 is caused by mutations in GJB1 (Connexin 32), a gap junction protein expressed in Schwann cells. It is X-linked — males are more severely affected than females. Crucially, CMTX1 shows no male-to-male transmission (unlike autosomal dominant CMT). Fathers pass the mutation to all daughters but no sons. NCS in males with CMTX1 shows intermediate conduction velocities (38–25 m/s range) — between the demyelinating and axonal groups.
CMT Type 4 (CMT4) — autosomal recessive, more severe
CMT4 subtypes are autosomal recessive — both copies of the gene must be mutated. These are rarer, tend to have earlier and more severe onset (often before age 5), and are more common in communities with higher rates of consanguinity. In Telangana and Andhra Pradesh, where consanguineous marriages are more prevalent, CMT4 subtypes (including GDAP1 and SH3TC2 mutations) should be considered in children with early-onset, severe neuropathy. Nerve biopsy may show specific features (onion bulb formations) helpful in classification.
Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) — the deletion counterpart of CMT1A
HNPP is caused by deletion of the same region of chromosome 17 that is duplicated in CMT1A. Instead of the uniform slowing of CMT1A, HNPP produces episodic focal neuropathies at pressure points: wrist (carpal tunnel), elbow (cubital tunnel), fibular neck (common peroneal nerve). A patient with recurrent carpal tunnel syndrome, multiple pressure palsies, or episodic focal neuropathies should have HNPP considered. The NCS shows conduction abnormalities at standard entrapment sites plus diffuse mild slowing.
Clinical Features
The four pillars of clinical recognition at KIMS — the pes cavus high-arched foot as the structural signature, the foot drop and steppage gait that brings most children to medical attention, the "inverted champagne bottle" distal leg wasting with relatively preserved thigh bulk, and the relatively mild sensory symptoms that distinguish CMT from acquired neuropathies.
Foot deformity — pes cavus is the structural signature of CMT
Pes cavus (high-arched foot) is the skeletal consequence of long-standing imbalance between intrinsic foot muscles (innervated by the medial and lateral plantar nerves, weakened early) and the extrinsic muscles (tibialis anterior and peroneus longus, better preserved initially). The imbalance pulls the foot into a high-arch, clawed-toe posture. In severe cases, the deformity requires orthopaedic correction (plantar fascia release, tendon transfer, calcaneal osteotomy). Pes cavus is present in virtually all patients with CMT1A by the time they are teenagers but may be subtle in early childhood.
Foot drop and the "steppage" gait
Weakness of the tibialis anterior (ankle dorsiflexion) and the peroneal muscles causes foot drop — inability to lift the front of the foot during walking. To avoid tripping, patients develop a "steppage" gait — excessively raising the knee to clear the foot from the ground. This gait pattern is characteristic and is often the first sign that brings a child to medical attention. In CMT1A, foot drop typically becomes apparent in the first or second decade of life.
"Inverted champagne bottle" appearance of the legs
Selective wasting of the distal leg muscles (peroneal group, gastrocnemius-soleus, and intrinsic foot muscles) while the proximal muscles (quadriceps, hamstrings) are relatively preserved gives the legs a characteristic shape — very thin below the knee with relatively normal thigh bulk. This has been described as "inverted champagne bottle" legs. In CMT1A, hand intrinsic muscle wasting (thenar and hypothenar eminence wasting) develops later, producing "claw hand" in advanced disease.
Sensory symptoms are mild in CMT compared to motor weakness
Unlike acquired neuropathies (diabetic, toxic), CMT produces relatively mild sensory symptoms. Patients may note mild numbness or reduced sensation in the feet, but severe burning pain is uncommon. This is because the nerve damage in CMT is a lifelong, slowly progressive process that the sensory system partially adapts to. However, vibration and proprioception (joint position sense) are reduced, contributing to unsteadiness on uneven surfaces and in the dark.
Diagnosis at KIMS
Diagnosis at KIMS
CMT is diagnosed at KIMS with a structured workflow that begins with electrophysiology to determine the demyelinating vs axonal pattern, proceeds to a targeted CMT gene panel that identifies the underlying mutation in 70–80% of typical cases, reserves nerve biopsy for selected unresolved cases, and assesses respiratory function in the rare CMT subtypes with diaphragm involvement :
NCS/EMG — the first and most important test
In demyelinating CMT (CMT type 1), NCS shows a characteristic pattern of uniformly slowed motor conduction velocity below 38 m/s across all nerves, with preserved or mildly reduced amplitudes. This uniform slowing supports the diagnosis of demyelinating CMT and classifies it as a type 1 (demyelinating) neuropathy, but NCS alone cannot confirm CMT1A specifically — multiple CMT1 subtypes can produce the same pattern, and genetic testing is required to identify the causative gene. This uniform pattern (as opposed to the focal slowing of entrapment neuropathies) is the electrophysiological hallmark. Family members can be screened with NCS: a slowed but asymptomatic sibling has subclinical CMT. CMT2 shows normal or near-normal velocity with reduced amplitudes. CMTX1 shows intermediate velocities in males (38–25 m/s).
CMT genetic panel
A CMT gene panel tests for the most common mutations simultaneously: PMP22 duplication/deletion (CMT1A/HNPP), MPZ (CMT1B), GJB1 (CMTX1), MFN2 (CMT2A), GDAP1, SH3TC2 (CMT4C), and others. PMP22 duplication is detected by MLPA (multiplex ligation-dependent probe amplification) or array CGH. The panel identifies the causative mutation in approximately 70–80% of clinically typical CMT cases. At KIMS, genetic testing is available and genetic counselling is provided alongside the result.
Nerve biopsy — selected cases only
Sural nerve biopsy at the ankle is reserved for cases where the genetic panel is negative, the NCS pattern is atypical, or a differential diagnosis (vasculitis, CIDP, amyloidosis) needs to be excluded. In CMT1, nerve biopsy shows "onion bulb" formations — concentric layers of Schwann cell processes surrounding demyelinated axons. In CMT2, the biopsy shows axonal loss with minimal demyelination. Nerve biopsy is rarely needed for the common CMT1A subtype.
Pulmonary function testing — selected severe cases
In rare CMT subtypes (particularly CMT with diaphragm involvement, and Dejerine-Sottas disease), respiratory muscle weakness can develop. Spirometry (FVC) and respiratory assessment is performed in CMT patients with dyspnoea on exertion or symptoms of nocturnal hypoventilation. This is uncommon in typical CMT1A.
Treatment
Treatment at KIMS
The KIMS CMT programme is built around five integrated management areas — custom-moulded AFOs (the most important functional intervention for foot drop), physiotherapy and exercise to preserve function and reduce fall risk, orthopaedic surgery for severe pes cavus deformity (plantar fascia release, tendon transfers, calcaneal osteotomy), strict avoidance of neurotoxic medications with a CMT drug-alert card, and genetic counselling for reproductive planning and cascade family testing.
AFOs, Physiotherapy, Orthopaedic Surgery, Neurotoxic-Drug Avoidance, and Genetic Counselling
Ankle-Foot Orthoses (AFOs): Custom-moulded AFOs are the most important functional intervention for CMT patients with foot drop. An AFO holds the foot and ankle at a 90-degree angle during the swing phase of walking, eliminating foot drop and the steppage gait. This prevents falls, reduces fatigue, and improves walking speed and distance. Carbon-fibre AFOs are lighter and preferred for active patients. AFOs are prescribed and fitted at the KIMS orthotics clinic in collaboration with a physiotherapist who assesses gait and determines the required orthosis type.
Physiotherapy and Exercise: Strengthening exercises for relatively preserved muscle groups, stretching of the Achilles tendon (to prevent or reduce contracture), proprioceptive training (balance exercises on unstable surfaces), and swimming or cycling (low-impact aerobic exercise) are all recommended. Physiotherapy does not reverse nerve damage in CMT but preserves function, delays loss of independence, and reduces fall risk. There is evidence that resistance exercise maintains muscle strength in CMT and slows functional decline.
Orthopaedic Surgery: Severe pes cavus with clawed toes that cannot be managed with AFOs may require surgical correction: plantar fascia release, proximal metatarsal osteotomy, calcaneal osteotomy, and toe interphalangeal joint fusions. Tibialis posterior tendon transfer to the dorsum of the foot can restore some active ankle dorsiflexion where the tibialis anterior is non-functional. These surgeries are planned at KIMS in collaboration with orthopaedic surgery.
Medications to Avoid in CMT: Several medications are neurotoxic and can cause significant, sometimes irreversible, worsening of CMT. The most important: vincristine (chemotherapy — absolute contraindication in CMT1A), paclitaxel and other taxanes, cisplatin, excessive vitamin B6 (pyridoxine above 200 mg/day), amiodarone, linezolid, nitrofurantoin, and isoniazid (without pyridoxine co-administration). At KIMS, a CMT "drug alert card" is provided to all patients to present to any treating physician or pharmacist.
Genetic Counselling: CMT1A is autosomal dominant with 50% risk of transmission to each child. Genetic counselling is provided at KIMS to discuss: the inheritance pattern of the confirmed mutation; reproductive options (natural conception with prenatal testing, preimplantation genetic diagnosis where available, or donor gametes); the typical severity and variability within the family; and the implications for asymptomatic family members who may wish to be tested.
Related Conditions
Charcot-Marie-Tooth disease belongs to the family of peripheral neuropathies evaluated and managed at KIMS Neuroscience. Explore related neuropathic conditions or return to the peripheral neuropathies hub.
FAQs
Frequently Asked Questions
The child who trips because of weak ankles. The family where multiple members have high-arched feet and thin calf muscles. The young adult whose neurologist says the nerve signals in the legs are very slow.
Charcot-Marie-Tooth disease is diagnosable with a single genetic test and manageable with the right orthoses and physiotherapy. At KIMS Hyderabad, genetic testing, NCS, and CMT multidisciplinary care are available in one centre. Call 040-44885000.
International enquiries: info@kimsneurosciences.com