Orthopedic surgical management of skeletal deformities in Cole-Carpenter syndrome: A case report of two siblings

INTRODUCTION

Carpenter syndrome is a rare inherited condition that is classified under the acrocephalopolysyndactyly group of disorders and is characterized by skeletal malformations and craniofacial abnormalities. It was first recorded in 1901 and then defined in clinical genetics. The condition is inherited in an autosomal recessive manner.^[1] Mutations in the RAB23 gene are the most frequently identified as the underlying cause. This gene is crucial for regulating the Sonic Hedgehog pathway, a signaling mechanism essential for brain and skeletal system development.^[2]

Patients with Carpenter syndrome usually have a number of clinical signs, such as craniosynostosis (early fusing of cranial sutures), polydactyly, brachydactyly, and syndactyly, as well as other manifestations, such as being short, overweight, or having heart defects from birth.^[3,4] Although musculoskeletal deformities affecting the limbs, including genu valgum, coxa valga, and pes varus, can substantially impair function, their management is rarely addressed in published literature.^[1] Cole-Carpenter syndrome 2 is a subtype of carpenter syndrome caused by a mutation in the SEC24D gene. It has craniosynostosis features, facial features similar to carpenter syndrome, in addition to osteogenesis imperfecta manifestations, which include bone fragility and recurrent fractures.^[5]

There are no standardized orthopedic therapy protocols due to the extreme rarity of this syndrome, with fewer than 100 cases described globally.^[2] The majority of case reports have concentrated on craniofacial and digital anomalies, while there is limited information regarding long bone deformities or orthopedic interventions.^[3]

This report focuses on two cases of Carpenter syndrome patients with severe limb deformities requiring surgical intervention. To expand the existing body of work on the surgical treatment of Carpenter syndrome, we will detail the clinical and radiological evaluation, surgical management, and early outcomes of these rare genetic disorders.

CASE REPORT

Case 1

A 6-year-old girl was referred to our institution with recurrent fractures, which is similar to osteogenesis imperfecta presentation with lower-limb deformities and pain. The case was diagnosed as a Cole-Carpenter syndrome by genetic testing, specifically whole-exome sequencing, which revealed a homozygous mutation in exon 18 of the SEC24D gene. The patient has two siblings who were similarly affected, and her parents are related through consanguinity. The patient was started on a daily growth hormone dose at the age of 2 years and received a bisphosphonate injection every 6 months.

She had multiple fractures, which were noticed by her parents at the age of 18 months following minimal trauma. The patient’s daily activities were affected by the pain in the lower extremities, but there was no limitation with upper-limb activity. She had dysmorphic features, with macrocephaly, frontal bossing, proptosis, micrognathia, and short stature. She has full elbow flexion and extension with full painless forearm supination and pronation. She was walking without a walking aid. Lower-limb examination revealed full knee and ankle motion, bilateral hindfoot valgus, and adducted forefeet. Radiographs demonstrated diffuse osteopenia, proximal ulnar pseudoarthrosis with distal ulna dysplasia. In lower limbs, she has bilateral tibial bowing, mild coxa valga, a partially healed proximal fibular fracture, pseudoarthrosis of the right fifth metatarsal, and fragmentation of the left fifth proximal phalanx [Figure 1].

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Figure 1:

Illustration of musculoskeletal deformities (Sibling 1). Radiographs showing diffuse osteopenia and metaphyseal irregularities. (a) Left and (b) right upper limbs with humerus deformity, radial head subluxation, distal ulnar dysplasia, and multiple non-/partially healed fractures. (c-e) Lower-limb radiographs show severe tibial bowing, fibular and (f) metatarsal fractures with pseudoarthrosis to the right fifth metatarsal.

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At the age of five, the patient underwent a corrective Sofield tibial osteotomy. The fibula had repetitive fractures at different levels, which facilitated tibial nail insertion and appeared as fibula osteotomies. The concept of the Fassier– Duval nail in this patient differed from its traditional use in osteogenesis imperfecta. In this case, it served primarily as an internal splint to stabilize the fracture and maintain deformity correction, allowing the bone to grow without developing malalignment. Postoperatively, the patient was on an above-knee full cast for a total of 6 weeks. During the 6-week follow-up visit, radiographs showed healing at the osteotomy site, with callus formation, and no implant failure or malalignment [Figure 2]. The patient was started on weight-bearing gradually.

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Figure 2:

Demonstration of lower extremities surgical correction using Fassier–Duval nail (sibling 1): Post-operative (a) anteroposterior and (b) lateral radiographs of the right lower extremities as well as (c) anteroposterior and (d) lateral of the left lower extremities, demonstrating surgical correction of bilateral tibial deformities with restoration of tibial alignment.

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During the following year, the patient had a fracture on the left side, and the same surgical intervention was done. At 2 years of follow-up, she demonstrated full non-painful mobility and weight-bearing capacity with no instability. Residual foot deformities were present but asymptomatic. Follow-up will continue until skeletal maturity. Intervention for upper extremities and feet deformity will be addressed in case it becomes symptomatic and affects her daily living.

Case 2

A 7-year-old male with a recent diagnosis of Carpenter syndrome was referred to our orthopedic clinic for evaluation of short stature and recurrent fractures. His diagnosis was genetically confirmed at our institution one year earlier. Whole-exome sequencing revealed a homozygous mutation in exon 18 of the SEC24D gene. He was started on growth hormone therapy to address the growth delay, in addition to bisphosphonate injections.

The patient appeared dysmorphic with characteristic craniofacial features, including macrocephaly, frontal bossing, proptosis, and micrognathia, along with disproportionate short stature. Lower limb assessment revealed bilateral genu valgum, externally rotated distal left tibia, and valgus heel positioning. The patient demonstrated abnormal gait with absent toe lift and asymmetric hip internal rotation (left: 70°, right: 40°). He was mobilizing with no walking aids. He was complaining of pain with prolonged mobilization secondary to his deformity.

Radiographic evaluation showed bilateral dislocation of the radial heads, with short and dysplastic distal ulnae, and bilateral valgus deformity of the tibiae. Multiple fractures were noted at various stages of healing [Figure 3].

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Figure 3:

Illustration of associated deformities in (sibling 2). Radiographs showing diffuse osteopenia and metaphyseal irregularities. (a and b) Anteroposterior and (c and d) lateral radiographs show multiple upper-limb fractures with radial head dislocation/subluxation and (e and f) anteroposterior and (g and h) lateral radiographs show lower-limb deformities with tibial bowing and numerous non-partially healed fractures.

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At the age of eight, the patient underwent staged bilateral tibial reconstruction. The first procedure involved a Sofield osteotomy at the center of rotation of angulation of the right tibia, with shortening, to maintain alignment for telescopic Fassier–Duval nail insertion. Three months later, a similar osteotomy and Fassier–Duval nail were performed on the left tibia. Postoperatively, the patient was immobilized in an above-knee cast for 6 weeks after each procedure. Healing of osteotomy sites was confirmed by radiograph. Gradual weight bearing was started after 6 weeks.

At follow-up, the patient reported satisfaction with the outcome. The deformities were significantly corrected, and he regained a full range of motion in his knees and ankles. He was able to ambulate independently without pain or functional limitation [Figure 4].

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Figures 4:

Surgical intervention using Fassier–Duval nail to correct lower-limb deformities in (sibling 2). Post-operative (a) anteroposterior and (b and c). Lateral radiographs of the lower extremities demonstrating surgical correction of bilateral tibial deformities with restoration of tibial alignment.

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DISCUSSION

Carpenter syndrome is a rare autosomal recessive disorder that is characterized by craniosynostosis, polydactyly, soft tissue syndactyly of the hands and feet, obesity, and variable degrees of intellectual disability.^[1] It was first described in 1901. Cole-Carpenter syndrome, a more severe subtype of Carpenter syndrome that was first described in 1987, is characterized by significant bone fragility, cranial deformities, growth failure, and recurrent fractures. Despite its distinct genetic and biochemical features, it has been classified within the broader spectrum of osteogenesis imperfecta-like syndromes, which exhibit orthopedic manifestations such as bone fragility and fractures, ligamentous laxity, short stature, and scoliosis secondary to abnormal collagen cross-linking.^[4] The musculoskeletal manifestations of Cole-Carpenter syndrome are underreported, despite the fact that craniofacial and developmental anomalies have been extensively characterized in the literature. To date, no exhaustive review has addressed the bony abnormalities associated with Carpenter syndrome or Cole-Carpenter syndrome nor has any study outlined a standardized orthopedic approach to deformity correction in affected individuals.

Both patients presented with multiple fractures and progressively worsening deformities of the lower limbs, including severe tibial bowing, valgus alignment, and poor fracture remodeling. These findings are consistent with previous reports documenting generalized osteopenia, metaphyseal irregularities, and skeletal dysplasia in Cole-Carpenter syndrome.^[3,4,6] Radiographs showed partially healed fractures and evidence of pseudoarthrosis in the metatarsals and fibula. In both cases, surgical management was necessitated by mechanical axis deviation, pain, and impaired gait. The orthopedic intervention followed classic principles of pediatric deformity correction, namely, osteotomy, alignment, and internal fixation. We chose the Fassier–Duval nail system for both patients, given its telescoping nature, compatibility with pediatric osteopenic bone, and effectiveness in other skeletal dysplasias, such as osteogenesis imperfecta.^[5]

This report presents the first documented case of staged bilateral tibial deformity correction in Cole-Carpenter syndrome utilizing Fassier–Duval nails, accompanied by a 3-year long-term follow-up. The surgical outcomes were positive for both patients, who achieved full weight-bearing mobility, pain-free ambulation, and maintained a range of motion without complications. The surgical outcomes were favorable in both patients, who achieved full weight-bearing mobility, pain-free ambulation, and preserved range of motion without complications.

Both patients demonstrated upper-limb abnormalities, specifically bilateral radial head dislocations and dysplastic distal ulnae, which were not addressed surgically owing to minimal functional impairment. Comparable upper extremity characteristics have been observed in patients with Cole-Carpenter syndrome and Carpenter syndrome, including elbow contractures and syndactyly, which have variable effects on functionality.^[7,8] Although our cases concentrated on lower-limb deformities, subsequent evaluations may necessitate intervention for upper-limb alignment, especially if pain or range-of-motion deficits arise.

The current literature remains sparse regarding orthopedic outcomes in Cole-Carpenter syndrome. Most published reports focus on craniofacial and hand surgery, with limited attention paid to long bone deformities, fracture healing, and gait disturbances.^[1-3,9] In several cases, bisphosphonate therapy has been used in an attempt to improve bone mineral density, although its efficacy in Cole-Carpenter syndrome remains unclear and was not part of our management strategy.^[6,7] Medical therapy alone does not correct alignment or prevent progression of deformity, underscoring the essential role of orthopedic intervention.

This report uniquely documents two siblings affected by Cole-Carpenter syndrome, both exhibiting aggressive musculoskeletal features and necessitating staged surgical correction. Familial cases are infrequently documented, underscoring the significance of prompt diagnosis and genetic counseling. Our surgical approach demonstrates that, despite severe deformity and poor bone quality, a non-painful gait with no lower limb deformity can be achieved through meticulous pre-operative planning, suitable implant selection, and multidisciplinary follow-up. Ideally, patients should be followed until skeletal maturity to address any symptomatic deformities that may arise in the future.

Our findings suggest that intramedullary fixation using Fassier–Duval nails is an effective surgical management option for long bone deformities in Cole-Carpenter syndrome. The approach provided robust structural support, facilitated growth, and significantly improved the quality of life for patients. The absence of standardized protocols and the lack of available data necessitate extensive multicenter collaboration to establish best practices for orthopedic care in Carpenter and Cole-Carpenter syndromes. Prompt identification of musculoskeletal involvement, timely intervention, and ongoing monitoring are essential for providing optimal care in this complex and vulnerable patient population.

CONCLUSION

Cole-Carpenter syndrome presents considerable orthopedic difficulties due to recurrent fractures, increasing deformities, and inadequate bone healing. This case series is the first bilateral staged Fassier–Duval procedure in Cole-Carpenter syndrome, demonstrating that planned deformity repair achieves positive long-term results, enhancing mobility and alignment. These findings underscore the importance of early orthopedic intervention and highlight the need for additional clinical data to inform treatment for this rare and complex condition. Long-term follow-up is recommended for upper-limb deformity, so appropriate intervention can be done in case it becomes symptomatic and affects daily living activities.