Pes Cavus - Causes

About 80% of cases are associated with a neurological disease. It always needs neurological investigation.

• Bailey and Love's Short Practice of Surgery, 28th Ed.

Classification of Causes

1. Neurological / Neuromuscular (most common - ~80%)

• Charcot-Marie-Tooth (CMT) disease - the single most common cause. It is a heterogeneous group of hereditary sensorimotor neuropathies caused by mutations in neural proteins affecting peripheral nerve conduction. The most common type (CMT-1) causes axon demyelination. It leads to characteristic weakness of the tibialis anterior and peroneus brevis, while the peroneus longus and tibialis posterior are relatively spared - this imbalance drives plantarflexion of the first ray and hindfoot varus.
• Hereditary sensory and motor neuropathies (other types)
• Post-poliomyelitis (static deformity)

• Unilateral pes cavus - always suspect a spinal cord lesion: diastematomyelia, spinal cord tumor, spinal dysraphism, or syrinx
• Spinal cord tumors
• Syringomyelia

• Cerebral palsy (static process but progressive contractures)
• Friedreich's ataxia - progressive ataxia with kyphosis, scoliosis, pes cavus, and hypertrophic cardiomyopathy
• Other cerebellar ataxias

2. Structural / Traumatic

• Malunion of calcaneus or talus fractures - varus malunions can produce a cavus foot
• Post-compartment syndrome - muscle imbalance following a compartment syndrome of the leg or foot
• Crush injuries of the foot
• Residual clubfoot - inadequately corrected or relapsed clubfoot deformities

3. Idiopathic

• A subtle, bilateral cavus foot may exist without any identifiable underlying disease - this is usually mild and presents without overt neurological findings. However, a neurological cause is eventually found in up to 66% of cases, so idiopathic is truly a diagnosis of exclusion.

Key Clinical Pointers

Pathomechanics (why the deformity develops)

1. Peroneus longus overpowers a weakened tibialis anterior → plantarflexion of the first metatarsal → forefoot pronation
2. Tibialis posterior overpowers a weakened peroneus brevis → hindfoot varus

Causes of Hammer Toe

Core Pathomechanism

• The extrinsic muscles (extensor digitorum longus - EDL, and flexor digitorum longus - FDL) overpower the intrinsic muscles (interossei and lumbricals)
• The EDL drives MTP joint extension
• The FDL drives PIP and DIP joint flexion
• FDL contracture is the key dynamic component driving the hammer toe deformity

Causes

1. Ill-fitting Footwear (most common)

• Tight or narrow toe box shoes crowd the toes, chronically forcing them into a flexed posture
• High heels shift weight to the forefoot and place MTP joints in extreme dorsiflexion
• Chronically elevated forefoot pressure permanently alters MTP joint position and causes stretching and tearing of the plantar fibrocartilaginous plates
• Over time this leads to flexible and eventually fixed deformity

2. Anatomical / Structural Factors

• Long second ray - a toe longer than the first bends and buckles within the shoe
• "Two-bone toe" - an anatomical variant where the middle phalanx is absent or fused, predisposing to buckling
• Hallux valgus (bunion) - the deviated great toe pushes against and displaces the second toe, causing it to buckle
• Pes cavus - hammer toes frequently accompany high-arched feet due to the shortened plantar aponeurosis and abnormal load distribution

3. Neuromuscular Disease (mainly cause claw toes, but also hammer toes)

• Charcot-Marie-Tooth disease - intrinsic muscle weakness allows extrinsic muscles to dominate; noted complication in CMT
• Cerebral palsy
• Post-compartment syndrome of the deep foot compartments - intrinsic muscle ischemia causes contracture
• Peripheral neuropathies (any cause)
• Medial/lateral plantar nerve laceration

4. Connective Tissue and Inflammatory Conditions

• Rheumatoid arthritis - synovitis leads to capsular distension, plantar plate attenuation, and MTP subluxation/dislocation progressing to deformity
• Connective tissue disorders (generalized ligamentous laxity)
• Plantar plate tear - disruption of the MTP plantar plate (the key stabiliser) causes the crossover/hammer toe deformity

5. Trauma

• Direct injury to the toe
• Malunion following phalangeal fractures
• Vascular injury to digital vessels

6. Metabolic / Systemic Conditions

• Diabetes mellitus - peripheral neuropathy leads to intrinsic muscle dysfunction; diabetic patients are also at high risk of ulceration over the deformity
• Myelomeningocele - decreased sensibility allows deformity to progress to ulceration

Summary Table

Key Point - Hammer Toe vs. Claw Toe

"Claw toes frequently are caused by neuromuscular diseases, and often a similar deformity is present in all toes, whereas in hammer toe deformity only one or two toes are involved."

• Campbell's Operative Orthopaedics, 15th Ed. 2026

MFN2-Related CMT2A (Charcot-Marie-Tooth Disease Type 2A)

1. Overview

• ~4% of all CMT disease
• ~20-30% of CMT2 (axonal) cases
• ~30-40% of genetically diagnosed axonal CMT

2. Genetics

• Indels, CNVs, duplication variants, and nonsense mutations tend to be more pathogenic
• GTPase domain mutations are particularly significant to protein structure and function
• About half of cases arise from a de novo mutation (no family history)

3. MFN2 Protein: Structure and Normal Function

• 757-amino acid transmembrane GTPase
• Anchored to the outer mitochondrial membrane via two adjacent transmembrane regions
• Member of the dynamin superfamily of large GTPases
• Homolog of Mitofusin-1 (MFN1)

1. Mitochondrial outer membrane fusion - together with MFN1, it mediates fusion of the outer mitochondrial membranes, essential for maintaining the mitochondrial network and quality control
2. Inner membrane fusion - works in concert with OPA1 (inner membrane GTPase)
3. Mitochondria-associated ER membrane (MAM) tethering - mediates ER-mitochondria contacts, regulating calcium homeostasis and lipid transfer
4. Mitophagy regulation - participates in the PINK1-Parkin-MFN2 pathway, marking damaged/depolarized mitochondria for autophagosomal degradation
5. Mitochondrial axonal transport - critical for delivering mitochondria to distal axons, which are especially energy-demanding

4. Pathomechanism

• Mitochondria cannot fuse properly → fragmented, dysfunctional mitochondrial networks
• Loss of fusion impairs mitochondrial quality control - damaged mitochondria accumulate
• Disrupted mitochondrial membrane potential and reduced ATP production

• Peripheral axons (especially the long sensory and motor axons to the feet) are particularly dependent on mitochondrial transport for energy
• MFN2 mutations alter axonal mitochondrial distribution - distal axons are starved of energy
• This explains the length-dependent pattern of neurological deficits (distal > proximal)

• ER-mitochondria contacts are impaired → disrupted calcium and lipid homeostasis
• This contributes to axonal stress and degeneration independent of bioenergetic failure

• Chronic axonal atrophy with subsequent regeneration (seen on sural nerve biopsy)
• Unlike CMT1 (which affects myelin/Schwann cells), CMT2A is a primary axonopathy - nerve conduction velocity is normal or near-normal because myelin is intact

5. Clinical Features

• Progressive distal muscle weakness and wasting (lower > upper limbs; legs before arms)
• Distal sensory loss (especially proprioception, vibration, then pain/temperature)
• Absent or diminished deep tendon reflexes (especially ankle jerks)
• Steppage gait (foot drop)
• Motor-predominant phenotype compared to other CMT2 types

• Pes cavus (cavovarus foot) - high arch with hindfoot varus
• Hammer toes - the most common associated toe deformity
• Scoliosis

• Optic nerve atrophy - in up to 9% of patients (Zuchner et al., 2006) - an important distinguishing feature
• Vocal cord involvement - occasionally
• Upper motor neuron dysfunction - occasionally (upper and lower MNS involvement = "intermediate" features)
• Pyramidal signs in some cases - reflecting CNS involvement beyond the peripheral nerve

• CMT2A is generally more severe than CMT1A
• Most patients have a severe phenotype; a subset has mild/late-onset disease
• Wheelchair dependency typically occurs in the 2nd-3rd decade

6. Electrodiagnostics

7. Diagnosis

1. Clinical features - early-onset severe distal weakness + pes cavus + hammer toes ± optic atrophy
2. NCS/EMG - axonal pattern with reduced CMAP/SNAP amplitudes, preserved NCV
3. Genetic testing - MFN2 gene sequencing (whole exome/gene panel); essential for confirmation
4. Family history - autosomal dominant pedigree, but de novo mutations are common
5. Sural nerve biopsy (rarely needed) - axonal atrophy with chronic regeneration, no onion bulbs (unlike CMT1)

8. Treatment

• Orthopaedic: AFOs (ankle-foot orthoses), custom footwear; surgical correction of cavovarus foot and hammer toes when needed
• Physiotherapy: Strengthening, stretching, balance training
• Ophthalmology: Regular screening for optic atrophy
• Genetic counselling for family members

• Mitofusin agonists (small molecules stabilizing MFN2 conformation) - most mechanistically direct approach
• Histone deacetylase inhibitors - preclinical models show benefit
• MFN1/MFN2 balance modulation - increasing MFN1 to compensate for MFN2 dysfunction
• SARM1 inhibitors - targeting axonal degeneration pathway
• Gene silencing and gene replacement therapies - early in vitro/in vivo results (Rizzo et al., 2023)

Recent Evidence

• Zhang et al., 2023 (Systematic Review) - 184 distinct MFN2 variants identified in 944 probands; GTPase domain mutations correlate most strongly with severity
• Alberti et al., 2024 (Review) - comprehensive update on pathogenesis, confirming roles of impaired mitochondrial fusion, MAM dysfunction, axonal transport failure, and mitophagy dysregulation