Hereditary Motor Sensory Neuropathies

Genetic Basis of HMSN/CMT:

The PMP22 gene that is duplicated in CMT1A is deleted in the reciprocal disorder hereditary neuropathy with liability to pressure palsies (HNPP) - a gene-dosage mirror image that examiners like to pair with CMT1A.

• Genetics: autosomal dominant deletion of one PMP22 allele on 17p11.2 (the same nonallelic homologous recombination event that, in the opposite direction, duplicates PMP22 to cause CMT1A).
• Clinical picture: recurrent, painless, often transient focal palsies precipitated by minor compression or stretch at common entrapment sites (the peroneal nerve at the fibular neck, ulnar at the elbow, median at the wrist, brachial plexus) - quite different from the slowly progressive symmetric cavovarus of CMT.
• Biopsy: focal sausage-shaped myelin thickenings called tomacula ("tomaculous neuropathy").

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The "Tripod" Concept of the Cavovarus Foot: The forefoot is described as a tripod resting on the 1st metatarsal head, the 5th metatarsal head, and the heel. In CMT the strong peroneus longus plantarflexes the 1st metatarsal (1st ray), driving the medial leg of the tripod down. To keep all three points on the ground, the hindfoot compensates by rolling into varus. This is the mechanical basis of the "forefoot-driven" hindfoot varus that the Coleman block test unmasks.

Sequence of Muscle Imbalance (drives the deformity):

Cellular and Molecular Mechanisms:

CMT pathophysiology depends on the specific genetic defect:

The characteristic foot deformity results from selective muscle weakness:

1. Peroneus Brevis: Weakens first (primary evertor of hindfoot).
2. Tibialis Posterior: Relatively preserved. Unopposed inversion pulls hindfoot into varus.
3. Peroneus Longus: Relatively preserved. Plantarflexes 1st metatarsal creating forefoot equinus.
4. Intrinsic Muscles: Early weakness. Long flexors/extensors become dominant causing claw toes.
5. Plantar Fascia: Secondary contracture contributes to arch elevation.

Net Result: Cavovarus foot (High arch + Hindfoot Varus + Claw toes + Forefoot adduction).

Progression Pattern:

• Distal-to-proximal weakness ('dying back' neuropathy).
• Lower limbs affected before upper limbs.
• Sensory loss follows similar pattern.
• Deformity progresses throughout growth and into adulthood.

CMT is a generalised neuropathy, so the foot is not the whole story - two examinable sites are easily overlooked.

• Hip dysplasia: acetabular dysplasia is a recognised association of CMT (reported in roughly the high single figures of patients) and is frequently missed because it is often painless. The threshold for a screening pelvis radiograph should be low, particularly in the growing child, because untreated dysplasia progresses to subluxation and early arthritis and is far easier to address when detected early (a peri-acetabular or femoral osteotomy) than late.
• The CMT hand: as the neuropathy ascends, the hand develops intrinsic-muscle wasting (first dorsal interosseous and thenar), a claw posture and weak pinch/grip, impairing fine tasks such as buttons and keys. Management is largely supportive (therapy, splints), with selective tendon transfers (for example to restore thumb opposition or correct clawing) in carefully chosen patients.
• Spine: scoliosis (already covered) is more common in early-onset and autosomal-recessive forms and warrants surveillance.

The cavovarus foot is the orthopaedic presentation, but a cavus foot is a red flag for an underlying neurological diagnosis until proven otherwise. Bilateral, symmetric, slowly progressive cavovarus with a positive family history points strongly to CMT, but the following must be considered and excluded.

• Short-term: Reliable deformity correction is achievable with the combined soft-tissue + osteotomy ("joint-sparing") approach.
• Long-term: In the longest published series (mean 26-year follow-up of joint-sparing reconstruction), the cavus correction was well maintained but most feet showed some radiographic recurrence of hindfoot varus, reflecting the progressive nature of CMT. Despite this, no patient required salvage triple arthrodesis and rates of degenerative change and reoperation were lower than historically reported after triple arthrodesis.
• Function: Surgery improves plantigrade stance, reduces lateral-border overload and recurrent sprains, and improves gait efficiency. Patient-reported physical function (SF-36) remains below age-matched norms because of the underlying neuropathy.
• Smoking: An independent predictor of worse pain and disability scores after CMT cavovarus reconstruction — counsel cessation.
• Counselling: Patients (and parents) must understand that surgery corrects the deformity but does not cure the neuropathy; progression and possible revision should be anticipated.

Global epidemiology:

• CMT/HMSN is the most common inherited neuropathy, with a widely cited population prevalence of approximately 1 in 2,500 (around 1 in 1,200 to 1 in 3,300 across studies).
• CMT1A (PMP22 duplication) is the single most common subtype; in population-based genetic series the PMP22 duplication accounts for roughly 10 to 60% of genetically defined cases.
• Cavovarus foot deformity is the dominant orthopaedic manifestation; scoliosis is more frequent in early-onset and autosomal-recessive forms (e.g. CMT4C).

Side-by-side practice guidance (no single national framework governs CMT foot surgery):