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.

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.

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.

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.

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.

[Intracranial hypertension in Proteus syndrome]. / Syndrome Proteus et hypertension intracrânienne.

Proteus syndrome, described for the first time in 1979, is a sporadic congenital poly-malformation syndrome named for its highly variable manifestations. We report the case of a 36-year-old male patient with several malformations including skull hyperostosis and huge frontal sinus hypertrophy compressing the brain. He complained of increasing headache for 5 years. Cerebrospinal fluid pressure monitoring revealed severe hypertension. The patient underwent frontoparietal craniectomy, which allowed partial decompression. Postoperatively headaches decreased and the intracranial pressure normalized. Proteus syndrome is a genetic disease with a mosaic pattern. Only a hundred cases have been reported, mostly in childhood. Common manifestations include disproportionate overgrowth of the limbs and the skull, various subcutaneous tumors, vascular, renal and pulmonary malformations. Brain abnormalities are not common in this syndrome. When present, retardation or seizure disorders are typically seen. Intracranial hypertension is described for the first time in this syndrome.

Morphological characterization of the breast in Proteus syndrome complicated by ductal carcinoma in situ.

Proteus syndrome (PS) is a severe, variable, and rare disorder with asymmetric and disproportionate overgrowth of body parts, cerebriform connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. It is associated with benign and occasionally malignant tumors. We report the first case of ductal carcinoma in situ (DCIS) in a 28-yr-old woman with PS who underwent a mastectomy for asymmetric overgrowth. The cut surface of the tissue showed a discrete, white, lobulated, solid mass with multiple cysts with occasional small polypoid nodules. Microscopically, the tissue was characterized by neoplastic and non-neoplastic changes. The former consisted of multiple intraductal papillomas and low-grade intraductal papillary, solid, and cribriform carcinoma. The non-neoplastic changes were characterized by cysts of various sizes, lined by cuboidal or apocrine cells, focally with epithelial papillary proliferation; the lumens contained eosinophilic, mucicarmine-positive, and PAS-positive material. Variable ductal proliferation and periductal, peri- and intra-lobular fibrosis with loose fibrous connective tissue was present. The carcinoma was positive for ER, PR, CK7, and MIB-1 (40%), and negative for p53 and CK20 staining. We conclude that DCIS may be one of the tumors associated with PS and that the proliferative phenotype serves as an initiator for carcinogenesis. This case highlights the difficulty of recognizing small foci of carcinoma in an asymmetrical overgrowth of the breast in a young woman with PS.

Proteus syndrome with huge tonsillar mass causing dysphagia: a rare case.

Proteus syndrome is a rare and highly variable hamartomatous syndrome that can affect multiple organ systems. It is characterized by hyperplasia of connective tissue, vascular malformations, epidermal naevi and hyperostosis. Most of the cases present to plastic and orthopaedic surgeons. Otolaryngologic presentations are minimal. We report such a rare case, which presented with a huge unilateral tonsillar mass causing dysphagia.

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.

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.

A minimal form of Proteus syndrome presenting with macrodactyly and hand hyperplasia.

Proteus syndrome is a rare congenital disorder characterized by progressive course and great variability of clinical presentation with partial gigantism of extremities, hemihyperplasia with macrocephaly, epidermal nevus, mesodermal hamartomas and the presence of peculiar cerebriform masses on the palms/soles. Many atypical cases have been reported and this is probably due to the mosaicism of the genetic disorder displaying different clinical features. We describe a patient with an extremely mild form of Proteus syndrome presenting macrodactyly and hyperplasia of one hand which was misdiagnosed until the age of 33 years.

Proteus syndrome: diagnosis and surgical management.

The congenital hamartomatous syndrome known as the "Proteus syndrome" (PS) manifests itself with regional giantism, lymphangiomatous hamartomas, and other variable features. Review of the medical literature shows approximately 50 cases reported to date. Since this syndrome has only recently been defined, the management of these patients has been speculative and often children are not treated. This report summarizes the characteristics of the PS and presents eight additional cases. All of the eight children had regional giantism with macrodactyly and skeletal hypertrophy. Asymmetrical leg length was pronounced in five children. All children had large lymphangiomas, the majority of which involved the trunk. Three of the children have been followed through adolescence, two into late childhood, and three into early childhood. In contrast to previous reports, we believe that early surgical reconstruction is necessary to reduce deformities due to the giantism and the large hamartomas. During extensive excisions, residual abnormal tissue is often needed in the reconstruction and it is not unusual for postoperative leakage of lymph to be prolonged. All of the children in this series have benefited both physically and emotionally from extensive surgical reconstruction.

Proteus syndrome.

A 34-year-old male patient was referred with a recalcitrant leg ulcer overlying an extensive vascular malformation, which had led several times to septic soft tissue infections. During his infancy he had been diagnosed to have Klippel-Trenaunay syndrome. Clinical examination revealed asymmetric hypertrophy of the lower extremities, an extensive portwine stain on the more severely affected left limb as well as prominent venous varicosities of both legs. Hands and feet showed striking cerebriform palmoplantar hypertrophy, and macrodactily with syndactily of several fingers. All toes had been amputated in early childhood due to extreme overgrowth and currently the patient walked on his forefeet in a prominent pes equinus deformity. Further symptoms consisted in several lipomas at both arms, another portwine stain at the left hemithorax and a single café-au-lait spot at the left scapula. Angio-magnetic resonance imaging scans of both legs showed an extensive venous-lymphatic vascular malformation involving the whole subcutis and infiltrating the muscle. The chronic wound was interpreted as venous stasis ulceration. Local percutaneous sclerotherapy of the dilated veins underneath the ulcer was discussed, but considered to carry a relevant risk of skin necrosis with consecutive progression of the wound. A conventional split-skin graft led to complete wound healing. Since, the patient consequently wears custom-made compression stockings and remained free from recurrences. The syndromatic constellation of palmoplantar overgrowth, multiple lipomas, giant fingers and toes, limb overgrowth, venous-lymphatic malformation and a café-au-lait spot led to the diagnosis of Proteus syndrome. The possible aetiology, clinical manifestations, differential diagnosis and management of this rare disorder are discussed.

Proteus syndrome: a case report.

Proteus syndrome is a rare genetic disorder, characterized by partial gigantism of the hands and/or feet, asymmetry of the limbs, plantar hyperplasia, multiple hamartomatous subcutaneous tumors, hyperostoses, and long bone overgrowth. A one day old Thai male infant is reported with macrosomia, hemihypertrophy of the left side of the face and left leg, large feet, macrodactyly of toes, plantar hyperplasia, large subcutaneous mass with a violet-red surface over the left side of the chest wall and a large port-wine stain involving the lateral aspect of the right chest wall. The clinical findings, diagnostic criteria, differential diagnosis, and management of the Proteus syndrome are reviewed.

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.