Quantification of Proteus syndrome-associated lung disease.

BACKGROUND: Proteus syndrome is an ultra-rare mosaic overgrowth disorder. Individuals with Proteus syndrome can develop emphysematous and cystic changes of the lung that may lead to progressive respiratory symptoms and require surgical intervention. This retrospective study seeks to quantify the radiographic features of Proteus syndrome-associated lung disease using computed tomography (CT) of the chest. The first method derives a Cystic Lung Score (CLS) by using a computer-aided diagnostic tool to quantify the fraction of cystic involvement of the lung. The second method yields a Clinician Visual Score (CVS), an observer reported scale of severity based on multiple radiographic features. The aim of this study was to determine if these measurements are associated with clinical symptoms, pulmonary function test (PFT) measurements, and if they may be used to assess progression of pulmonary disease. RESULTS: One hundred and thirteen imaging studies from 44 individuals with Proteus syndrome were included. Dyspnea and oxygen use were each associated with higher CLS (p = 0.001 and < 0.001, respectively) and higher CVS (p < 0.001 and < 0.001). Decreases in percent predicted FVC, FEV1, and DLCO each correlated with increased CLS and CVS. The annual increase of CLS in children, 5.6, was significantly greater than in adults, 1.6. (p = 0.03). The annual increase in CVS in children, 0.4, was similar to adults, 0.2 (p = 0.36). CONCLUSIONS: Proteus syndrome-associated lung disease is progressive. The rate of cystic progression is increased in children. Increased scores in CLS and CVS were associated with clinical symptoms and decreased pulmonary function. Both methods were able to detect change over time and were associated with clinically meaningful outcomes which may enable their use in interventional studies.

Phenotypic Features of Cystic Lung Disease in Proteus Syndrome: A Clinical Trial.

Rationale: Limited information is available regarding cystic lung disease in Proteus syndrome, a rare overgrowth disorder caused by a somatic activating variant in AKT1. Objectives: To define the phenotype of cystic lung disease in Proteus syndrome. Methods: Medical records, pulmonary function tests, and chest computed tomography of 39 individuals with Proteus syndrome evaluated at a single center were retrospectively reviewed. Lung histopathology from five affected individuals was examined. Results: Cystic lung disease affected 26 (67%) of 39 individuals. The mean age of affected individuals was 17.1 years. The lung cysts varied in size and location. Focal regions of heterogeneous lung parenchyma resembling emphysema were found in 81% of affected individuals. Mass effect was seen in 12% of affected individuals; pneumothorax occurred in one. Dyspnea and respiratory infections were reported by 38% and 35% of affected individuals, respectively. Abnormal pulmonary function and scoliosis were found in 96% of affected individuals. Lung disease progressed in seven of 10 affected individuals, and all five affected individuals younger than 20 years of age had progressive cystic lung disease. Three affected individuals had symptomatic improvement after lung resection. Histopathology showed cystic air space enlargement of varying severity. Conclusions: Cystic lung disease is common in Proteus syndrome and is likely to progress in affected individuals younger than 20 years of age. Screening asymptomatic individuals with Proteus syndrome for cystic lung disease is indicated. Surgical lung resection is a therapeutic option for affected individuals with severe disease. Clinical trial registered with www.clinicaltrials.gov (NCT00001403).

Phenotype and Surgical Treatment in a Case of Proteus Syndrome With Craniofacial and Oral Findings.

BACKGROUND/AIM: Proteus syndrome is a sporadic disease that is particularly noticeable due to the disproportional growth of body segments. The disease is a genetic mosaic. The mutations can arise from any of the germ layers, an explanation of the very variable phenotype. The aim of this report is to communicate the diagnosis and management of an unusual case of Proteus Syndrome with special attention to oral and craniofacial findings. CASE REPORT: A 15-year-old patient was referred for surgical treatment of pronounced skull malformations and correction of oral mucosal hyperplasia. Treatment caused significant improvement in facial appearance and oral soft tissue conditions. CONCLUSION: Surgical measures adapted to the local findings and symptoms can often relieve severe disfigurement of the patient.

Severe gynaecological involvement in Proteus Syndrome.

Proteus Syndrome is a rare complex overgrowth syndrome. We report a young female patient with Proteus Syndrome due to AKT1 mutation c.49G > A (p.Glu17Lys), presenting with a severe gynaecological involvement which necessitated a complete hysterectomy and a left adnexectomy. Cases of gynecological involvements in Proteus Syndrome are rare, not well known by physicians while they can be potentially severe.

Surgical correction of kyphotic deformity in a patient with Proteus syndrome.

BACKGROUND CONTEXT: Proteus syndrome (PS) is an extremely rare congenital disorder causing asymmetric overgrowth of different tissues. The etiology remains unclear. Limb deformities are common and often necessitate amputations. Only a few cases associated with spinal deformities have been described. PURPOSE: The aim was to report a rare case of PS associated with spinal deformity and its surgical management. STUDY DESIGN: A case of young boy with PS causing vertebral hypertrophy and kyphoscoliotic deformity, which was surgically corrected, is presented. METHODS: The patient was assessed clinically and with whole spine plain radiographs, computed tomography, and magnetic resonance imaging. Surgical correction was performed. RESULTS: Satisfactory correction of the deformity was achieved by posterior spinal fusion with instrumentation from T4-L5, five Ponte osteotomies T8-L1, and an L2 pedicle subtraction osteotomy. The kyphosis was corrected from 87° to 55°; there was improvement in all spinopelvic parameters. One year after surgery, there was maintenance of the deformity correction with no deterioration of the sagittal balance, and the patient was free of pain and had no loss of neurologic function. CONCLUSIONS: Proteus syndrome can be associated with spinal stenosis and deformity. Although the syndrome can be progressive in nature, the symptomatic spinal pathology should be treated appropriately.

Proteus syndrome: what the anesthetist should know.

Proteus syndrome (PS), a rare hamartomatous disorder, manifests itself in asymmetric and disproportionate overgrowth of multiple body tissues. Because of complexity of the disorder, the anesthetic problems encountered during patients' perioperative management are very varied. We discuss the case of a 14-year-old adolescent boy diagnosed with PS who underwent corrective osteotomy of right knee joint under subarachnoid block. The salient points the anesthetists need to be aware of while caring for patients with PS are highlighted.

Síndrome de Proteus: relato de casos / Proteus Syndrome: case reports

INTRODUÇÃO: A síndrome de Proteus é uma doença complexa e rara, classificada nos grupo das hamartoses. Foi primeiramente descrita em dois pacientes, em 1979, por Cohen e Hayden. Existe dificuldade no diagnóstico, sendo comum a confusão com síndromes de Klippel-Trenaunay-Weber, neurofibromatose ou Stuge-Weber. Apresentamos dois casos tratados no Serviço de Cirurgia Plástica e Reparadora da Universidade Federal do Paraná. MÉTODO: Paciente masculino (caso 1), que chegou ao serviço aos 6 anos de idade, tendo como principais apresentações lipomatoses e assimetrias. A segunda paciente (caso 2) deu entrada no serviço com 20 anos de idade e diagnóstico de síndrome de Klippel-Trenaunay-Weber, que posteriormente mostrou se tratar de síndrome de Proteus. CONCLUSÃO: A hipótese etiológica mais aceita para a doença é genética. Acredita-se que exista mosaicismo somático e que a doença seja letal no estado não mosaico. Morte prematura é bastante frequente. Entretanto, a sequela mais comum é a ocorrência de tumores incomuns. O cuidado dos pacientes portadores da síndrome é um desafio devido às suas consequências médicas e psicossociais.

INTRODUCTION: Proteus syndrome is a complex and rare disorder classified as a hamartomatous disease. It was first described in two patients in 1979, by Cohen and Hayden. Proteus syndrome is difficult to diagnose, and is often confused with Klippel-Trenaunay-Weber syndrome, neurofibromatosis, or Sturge-Weber syndrome. In this study we describe two patients who were treated at the Plastic and Reconstructive Surgery Service of the Federal University of Paraná. METHOD: A 6-year-old male patient (case 1) presented to the Service with lipomatosis and asymmetry, as the primary findings. A 20-year-old (case 2) was admitted to the Service with a diagnosis of Klippel-Trenaunay-Weber syndrome, which later was shown to be Proteus syndrome. CONCLUSION: The etiological hypothesis that is most accepted for this disease is genetic. It is believed that somatic mosaicism may occur during pathogenesis, which can be lethal in the mosaic state. Premature death is common. However, the most common sequelae are the occurrence of unusual tumors. The care of patients with this syndrome is a challenge due to medical and psychosocial consequences.

Fronto-temporal cerebriform connective tissue nevus in Proteus syndrome.

Proteus syndrome is one of the very rare syndromes with occurrence of cerebriform connective tissue nevus. The aim of the present manuscript was to present a case of Proteus syndrome in an unusual facial location, which to the best of our knowledge, is being reported for the first time. The unusual occurrence further strengthens the mosaical basis of its etiopathogenesis.

Syndromes with focal overgrowth in infancy: diagnostic approach and surgical treatment.

Syndromes with focal overgrowth are sporadic diseases and comprise Proteus syndrome and congenital lipomatous overgrowth, vascular malformations, and epidermal naevi (CLOVE) syndrome, and isolated hemihyperplasia. We describe 3 children classified according to standard criteria with dysregulated growth of various tissues that was excised, together with excess toes, and tumours. Correct classification facilitates diagnosis and operations. Interdisciplinary treatment and follow-up are recommended to prevent disfiguration.

A computer-assisted diagnostic and treatment concept to increase accuracy and safety in the extracranial correction of cranial vault asymmetries.

PURPOSE: Proteus syndrome is described as a progressive, asymmetric, disproportional overgrowth of various parts of the body. The theory of somatic mosaicism is widely accepted to be the cause of this disease. Affected patients present very heterogeneous symptoms, but in about 30% craniofacial deformities are the leading clinical features. Because no causal therapy exists, treatment options are limited to surgical improvement of functional constraints. MATERIALS AND METHODS: A computer-assisted method was used to increase the accuracy and safety of bone removal in the extracranial correction of cranial vault asymmetries. Descriptions of the diagnosis, preoperative planning, and intraoperative management of craniofacial dysmorphia caused by Proteus syndrome in a 6-year-old boy are presented. After computed tomography-based generation of a virtual 3-dimensional (3D) model of the patient and a haptic stereolithographic model to display the special pathology, flow-sensitized 4-dimensional magnetic resonance imaging was performed to clarify the properties of vascular formation inside the hyperostosis. To transfer the mathematically optimized preoperative planning of a new skull shape to the patient, a surgical guide was fabricated by rapid manufacturing. Intraoperative 3D real-time navigation was installed as an additional visualization and security feature. RESULTS: The surgery could be performed safely and quickly. Postoperative imaging showed that the surgical plan was realized with high accuracy. CONCLUSION: This newly developed and validated method can be successfully implemented in the operating room environment.

Macrodystrophia lipomatosa involving multiple nerves.

Macrodystrophia lipomatosa (MDL), a rare congenital disorder, is considered by some to be a localized form of Proteus syndrome. The implication of the PTEN (phosphatase and tensin homolog deleted on chromosome 10) gene in both strengthens this belief. We present a case who had MDL in multiple nerve territories--all on the same side of the body--with hypertrophy of mainly fibroadipose tissue throughout their distribution, thus pointing to a form of localized hemihypertrophy; both hemihypertrophy and lipomatous tumors are components of Proteus syndrome.

Management of craniofacial hyperostosis in Proteus syndrome.

Proteus syndrome is a rare congenital hamartomatous condition that is characterized by a wide range of malformations, occasionally involving the head and the face. Skin and skeletal developmental malformations are common and may be manifested in significant physical anomalies. In this report, we describe the cases of 2 patients affected by this condition. For one patient, a recurrence occurred 4 years after the elimination of cranial hyperostosis. In the second patient, although we observed macrosomia and peculiar countenance in the context of craniofacial hyperostosis, the patient did not visit a clinic for approximately 50 years before seeking treatment. The management of the craniofacial involvement is described, and a literature overview is presented.

Proteus syndrome: a case report.

Proteus syndrome is a rare, sporadically occurring hamartomatous disorder with complex multisystem involvement and wide clinical variability. Clinical characteristics include craniofacial abnormalities; asymmetrical overgrowth of the trunk, limbs, and digits; lipomas; and vascular malformations. Cystic lung disease is noted in approximately 10 per cent of patients. These cystic malformations may lead to cystic pulmonary emphysema, which may cause significant morbidity for the patient. We describe the case of a 27-year-old woman with known Proteus syndrome who developed acute on chronic respiratory failure. Subsequent CT scan of the chest was significant for extensive bullous disease with nearly complete replacement of the right lung tissue. Our operative management and the patient's clinical course are described.

Pediatric chest wall and breast deformities.

Pediatric chest wall and breast deformities present as a wide spectrum of anomalies, and often occur coincidentally. Chest wall abnormalities fall into two categories, congenital (which are largely hypoplastic) and deformational (including both chest wall malignancies and postoperative abnormalities). Breast abnormalities can be categorized into three groups, including hypoplastic, hyperplastic, and deformational anomalies. Hypoplastic breast anomalies require reconstruction with augmentation techniques and are often associated with significant reoperative rates, as are deformational anomalies; hyperplastic abnormalities require reduction techniques and are less likely to require reoperation. Considerations about surgical correction of pediatric chest wall and breast deformities often require coordinated efforts between pediatric and pediatric plastic surgeons with anticipation of continued growth of the child and careful timing for treatment to maximize functional and aesthetic outcomes.

Overgrowth conditions: a diagnostic and therapeutic conundrum.

Over the past five decades, one of the major problems in the treatment of overgrowth syndromes of the hand has been classification. Currently, a number of specific conditions with known natural histories have been delineated and reviewed. Treatment is highly individualized. Amputation is still recommended for grotesque deformities of the upper limb. Early aggressive surgery, when indicated, will improve contour, function, and appearance. Specific therapeutic techniques include radical debulking, microvascular neurolysis, vascular reconstruction, epiphysiodesis, and, in some cases, thumb or digit replacement. Long-term outcomes remain in the good-to-fair range and are dependent upon the condition, reconstructive techniques employed, age of patient, and the severity of deformity.