Severe Multifocal Noninfectious Wound Dehiscence After Cavovarus Reconstruction in TRPV4-Associated Charcot-Marie-Tooth Disease Type 2C: A Case Report

Abstract

Background

Charcot-Marie-Tooth disease (CMT) commonly produces progressive cavovarus/equinovarus deformity, and severe pediatric deformity may require complex reconstruction when bracing and therapy fail. Postoperative wound complications can occur after extensive hindfoot/midfoot surgery, but genotype-specific factors influencing wound healing remain poorly defined. Charcot-Marie-Tooth disease type 2C (CMT2C) is associated with transient receptor potential vanilloid 4 (TRPV4) variants, and experimental data suggest that TRPV4 signaling may influence fibroblast behavior and extracellular matrix deposition

Case

A 10-year-old girl with genetically confirmed CMT2C due to TRPV4 c.806G>A (p.Arg269His) presented with progressive ambulatory difficulty, severe bilateral stiff equinovarus (left worse), and a left knee flexion contracture (~25°). Weightbearing cone-beam computed tomography confirmed severe left cavovarus deformity. She underwent left anterior distal femoral hemiepiphysiodesis followed by complex left foot/ankle reconstruction, including Achilles Z-lengthening with posterior capsulotomy, multiple soft-tissue releases, posterior tibial tendon transfer to the lateral cuneiform, talonavicular release, peroneus longus-to-brevis transfer, and calcaneocuboid fusion. Within weeks, she developed severe multifocal wound dehiscence across multiple incision sites without clinical or microbiologic evidence of infection. She required readmission, serial debridements, and negative-pressure wound therapy. Adjunct dermal punch-biopsy-derived fibroblast explant culture showed delayed early outgrowth and reduced adherence/spread versus control, with preserved proliferation after passage. Plastic surgery performed operative debridement; perfusion imaging confirmed viable tissue, and biodegradable temporizing matrix was applied to key wounds with bridged vacuum-assisted closure, resulting in wound healing with long-term follow-up.

Conclusion

This case highlights unusually severe, noninfectious, multifocal wound dehiscence following technically appropriate, consensus-guided reconstruction in a child with TRPV4-associated CMT2C. Although causality cannot be established, the complication pattern raises the possibility of genotype-associated wound-healing vulnerability and supports heightened postoperative surveillance, early multidisciplinary involvement, and consideration of staged reconstruction in similarly high-risk patients.

Level of Evidence

Therapeutic, Level V (Case Report)

Introduction

“Charcot-Marie-Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of hereditary motor and sensory neuropathies characterized by progressive distal weakness, muscle atrophy, and sensory impairment . . ..”

Charcot-Marie-Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of hereditary motor and sensory neuropathies characterized by progressive distal weakness, muscle atrophy, and sensory impairment, often leading to cavovarus and equinovarus deformities of the foot and ankle. The prevalence of CMT is estimated at approximately 1 in 2500 individuals worldwide, encompassing numerous subtypes defined by distinct genetic etiologies that influence phenotype and disease course.^1,2 In children, these neuromuscular deficits intersect with ongoing growth and musculoskeletal development, which can magnify deformity progression and complicate orthopaedic management.

Initial treatment typically emphasizes nonoperative strategies, including orthotic bracing and targeted physiotherapy, to improve function, optimize alignment, and delay or avoid surgery when feasible. ³ However, conservative measures may be insufficient in the setting of severe or unbraceable deformity, progressive functional limitation, or pain, prompting consideration of reconstructive procedures aimed at restoring a plantigrade, stable limb.

Postoperative wound complications are recognized risks after complex hindfoot and midfoot reconstruction, and the biologic factors that may influence wound healing in specific CMT genotypes remain incompletely defined. Charcot-Marie-Tooth disease type 2C (CMT2C) is associated with mutations in the transient receptor potential vanilloid ⁴ (TRPV4) gene. Transient receptor potential vanilloid 4 has been implicated in mechanotransduction pathways relevant to tissue repair, including regulation of myofibroblast activity and collagen deposition,4 and experimental models suggest that disruption of TRPV4 signaling can alter wound-healing dynamics. ⁵ Although these data do not establish genotype-specific surgical risk in CMT, they raise the possibility that certain TRPV4 variants could influence postoperative soft-tissue recovery.

We report a child with genetically confirmed CMT2C (TRPV4 mutation) who developed severe, noninfectious wound dehiscence after extensive lower extremity reconstruction. This hypothesis-generating case suggests a possible genotype-related susceptibility to wound breakdown after major deformity correction and underscores the need for careful operative planning and close postoperative wound monitoring in similar patients.

Case Presentation

A 10-year-old girl with genetically confirmed CMT2C was evaluated for progressive ambulatory difficulty due to severe bilateral foot deformities and a left knee flexion contracture. Prior genetic testing identified a TRPV4 variant, c.806G>A (p.Arg269His). Her history was otherwise unremarkable. Despite prolonged nonoperative management, including structured physical therapy and bracing, her deformities progressed, resulting in worsening function. There was no known family history of neuromuscular disease.

On physical examination, the patient has bilateral stiff equinovarus (left worse) (Figure 1) and knee flexion contractures (~25° on the left and near-neutral extension on the right). Gait shows hand-assisted knee extension, indicating CMT2C-related quadriceps/proximal weakness. Weightbearing cone-beam computed tomography scan confirmed severe left cavovarus deformity (Figure 2). Due to progression and failed conservative care, surgery was indicated to restore function and improve mobility.

Figure 1.

Preoperative standing clinical photograph demonstrating bilateral rigid equinovarus (cavovarus) foot deformity, left worse than right, with inability to achieve a plantigrade stance.

Figure 2.

Weightbearing cone-beam CT (3D volume-rendered lateral reconstruction) of the left foot and ankle demonstrating severe cavovarus deformity.

Under general anesthesia with prophylactic antibiotics, she underwent anterior distal femoral hemiepiphysiodesis for the left knee contracture via 2 small medial and lateral incisions with cannulated screw fixation. She then proceeded to complex left foot and ankle reconstruction, beginning with posterior leg exposure of the Achilles tendon through a longitudinal incision over prior scarring. Extensive scar tissue necessitated Achilles Z-lengthening, and persistent equinus required posterior capsulotomy to obtain limited dorsiflexion. Percutaneous flexor tenotomies of the lesser toes were performed for digital contractures. Via a posteromedial approach, the posterior tibial tendon was found to be scarred/nonfunctional and was dissected and transferred through the interosseous membrane to the lateral cuneiform. A talonavicular arthrotomy with release of contracted ligamentous structures was performed to address hindfoot contracture, along with hallux flexor tenotomy, abductor fascia release, and plantar fascia release under direct visualization. Lateral hindfoot instability was addressed with exposure of the calcaneocuboid joint and peroneal tendons, followed by calcaneocuboid fusion using nitinol staples and peroneus longus-to-brevis transfer to augment lateral stability. Given the severity of the deformity and extensive motor deficit, fusion was the only viable intervention to achieve a stable, plantigrade foot. A tourniquet was used intermittently for approximately 2 hours and 6 minutes during the 6-hour procedure, meticulous hemostasis was achieved, and the extremity was immobilized in a well-padded splint with reassuring perfusion postoperatively.

Early recovery was initially uncomplicated; however, within weeks she developed multifocal wound dehiscence involving the distal anterior tibia (1 × 1.5 cm), plantar foot (1 × 0.5 cm), proximal medial instep (3 × 2 cm), and distal medial instep (1 × 2 cm), each demonstrating healthy granulation tissue without exposed critical structures. A larger lateral hindfoot wound (5 × 3 cm) demonstrated a <1 cm area of exposed tendon at its proximal aspect, with additional eschar over the posterior heel and the dorsum of the proximal hindfoot confluent with the proximal lateral wound (Figure 3).

Figure 3.

Multifocal postoperative wound dehiscence developing within weeks after left foot/ankle reconstruction. (A) Distal anterior tibial dehiscence (~1 × 1.5 cm) with a healthy granulating wound bed (no eschar). (B) Medial instep dehiscence (proximal medial instep, ~3 × 2 cm, with associated medial incision breakdown) demonstrating granulation tissue without exposed critical structures. (C) Lateral hindfoot wound (~5 × 3 cm) with surrounding posterior heel/proximal hindfoot eschar and a focal <1 cm area of exposed tendon proximally (not visible in this image). (D) Plantar foot dehiscence (~1 × 0.5 cm) shown with scale.

Given the extent of breakdown, she was readmitted for intensive wound management. Serial debridement and negative-pressure wound therapy (NPWT) were initiated, and there was no clinical evidence of infection; wound cultures showed no growth. Given the unexpectedly diffuse, noninfectious wound breakdown, adjunct tissue analysis performed in Sweden was reviewed from a dermal punch-biopsy-derived primary fibroblast explant culture in the setting of TRPV4 c.806G>A (p.Arg269His). Compared with parallel control, the TRPV4-variant culture demonstrated delayed explant outgrowth with reduced early adherence/spread, while proliferation after initial passage appeared preserved.

Plastic surgery was consulted for full-thickness eschars near the lateral malleolus and proximal dorsal foot, specifically to protect a nearby tendon transfer. They recommended nutritional optimization (calorie count, serial prealbumin/C-reactive protein, and multivitamin/zinc/A/C/B-complex supplementation) alongside NPWT.

The patient subsequently underwent operative wound debridement to the level of skin, fascia, and tendon. SPY perfusion angiography confirmed viable perfusion beneath the dorsal eschar; consequently, a conservative approach was maintained due to known healing concerns. Findings included a focal <1 cm area of exposed tendon in the lateral wound but no exposed hardware or bone.

A biodegradable temporizing matrix (BTM) was applied to the lateral hindfoot and proximal medial instep wounds, secured, and dressed with a bridged vacuum-assisted closure (VAC). Remaining smaller wounds received nonadherent petrolatum gauze and dry sterile dressings. Postoperatively, the limb was protected in a boot with strict pressure-point offloading.

Following BTM placement and bridged VAC therapy, she continued close outpatient wound surveillance with serial dressing/VAC management, strict immobilization and offloading, and ongoing nutritional optimization. The wounds demonstrated progressive granulation and soft-tissue coverage with gradual epithelialization, allowing eventual discontinuation of NPWT and transition to standard nonadherent dressings until closure. At 15-month follow-up, patient-provided photographs demonstrated complete healing of all incision and dehiscence sites and a stable, plantigrade foot resting flat on the ground, without recurrent breakdown (Figure 4). Contemporaneous 15-month follow-up dorsoplantar radiographs demonstrated maintained correction with improved overall alignment and retained calcaneocuboid arthrodesis fixation (nitinol staple) (Figure 5).

Figure 4.

Patient-provided weightbearing photograph at 15 months demonstrating complete soft-tissue healing and a stable, plantigrade foot resting flat on the ground without recurrent breakdown.

Figure 5.

Dorsoplantar (DP) radiograph of the left foot at 15-month follow-up demonstrating improved overall alignment with retained calcaneocuboid fusion staple.

Discussion

Surgical reconstruction for CMT deformity can produce meaningful functional improvement, but, as with any major cavovarus correction, it carries risk for postoperative complications. In this case, the reconstructive goals were achieved from a mechanical and alignment standpoint, yet the postoperative course was dominated by unexpected, multifocal, and severe wound dehiscence involving multiple incisions, occurring without evidence of infection and far exceeding the typical magnitude of wound-related complications seen after CMT reconstruction.

Published surgical series suggest that early postoperative complications after CMT reconstruction are generally infrequent and most commonly include superficial or deep infection, isolated superficial dehiscence, or unplanned hardware removal. For example, in a retrospective cohort of 89 patients undergoing CMT reconstructive surgery, the overall complication rate was approximately 8%, including 3 postoperative infections and 1 superficial wound dehiscence. ⁶ Importantly, the breadth and severity of wound breakdown observed in the present case are not represented in that experience, underscoring the atypical nature of this complication pattern.

The operative strategy and sequence used in this patient were consistent with established consensus recommendations and expert-driven algorithms for CMT reconstruction.^7-9 The procedure was technically executed without intraoperative mishap, and tourniquet utilization was intermittent and not prolonged relative to the overall operative duration. Therefore, while the length of the incision and the deep tissue work required for such a severe deformity can make any patient’s wound vulnerable, the fact that multiple sites opened up without infection suggests that the patient’s own underlying health factors played a significant role.

This case is presented specifically because CMT2C associated with TRPV4 mutation may represent a subgroup with distinct wound-healing biology. TRPV4 is implicated in mechanotransduction pathways relevant to fibroblast behavior and extracellular matrix deposition, and experimental data have linked altered TRPV4 signaling to impaired wound-healing dynamics, including fibroblast migration and collagen-related processes.^4,5 In our patient, the Sweden fibroblast explant observations—impaired early adherence/spread despite preserved proliferation—are directionally consistent with a potential early-phase wound-healing vulnerability in TRPV4-associated CMT2C; however, these qualitative findings are hypothesis-generating and require targeted functional validation before any causal inference.

In the present case, the clinical phenotype, severe wound breakdown without infection, involving multiple incisions and requiring prolonged advanced wound care, aligns with the possibility of intrinsic soft-tissue healing vulnerability rather than a complication attributable to infection, technical error, or clearly excessive ischemic exposure. That said, this report cannot establish causality; it can only highlight a plausible association and the need for heightened vigilance.

From a practical standpoint, the clinical takeaway is cautionary: in patients with TRPV4-associated CMT2C who require extensive correction, surgeons may wish to consider strategies that reduce soft-tissue burden at a single setting, including a staged reconstruction approach for very large deformities, alongside early multidisciplinary involvement and proactive escalation to advanced wound management should delayed healing appear.

Conclusions

We report a child with genetically confirmed CMT2C (TRPV4 mutation) who developed severe, multifocal, noninfectious wound dehiscence after technically appropriate, consensus-guided reconstruction of an extremely severe deformity performed at a high-volume CMT referral center with extensive surgical experience. Although this single case cannot establish causality, the magnitude and distribution of wound breakdown, despite the absence of infection or intraoperative adverse events, raises the possibility that TRPV4-associated CMT2C may confer increased vulnerability to postoperative wound-healing complications in select patients. For similarly severe deformities in patients with CMT2C/TRPV4, surgeons may consider staged reconstruction to reduce soft-tissue burden per setting and should maintain a low threshold for early multidisciplinary wound management escalation if healing deviates from the expected course.