Cerebriform Connective Tissue Nevus Research Articles

Spinal Anesthetic Management for Proteus Syndrome: A Case Report

Proteus syndrome is a rare, complex, and progressive disorder characterized by tissue overgrowth, deformities, and vascular anomalies. We present a case of a 56-year-old patient with Proteus syndrome who underwent successful incision and drainage an ulcerative lesion on a Cerebriform connective tissue nevus on the left plantar surface under spinal anesthesia. The patient had a history of mild lumbar scoliosis and a previous hospitalization for pulmonary embolism. Due to the patient's difficult airway and increased risk of thromboembolism, spinal anesthesia was chosen as the anesthetic technique. The procedure was carried out without complications, and the patient had a satisfactory postoperative recovery.

Proteus Syndrome: Case Report with Anatomopathological Correlation

Background Proteus syndrome is characterized by a progressive segmental or patchy growth of bone, skin, adipose tissue, and central nervous system, associated with a wide range of neoplasms, pulmonary pathology, and thrombotic risk. The main histological findings are diffuse patchy overgrowth of skin and subcutaneous tissue, plantar cerebriform connective tissue nevus, and ossification defects. Case report: We present a patient that met the clinical and histological criteria necessary for the diagnosis of the disease. He required multiple surgical interventions, including amputation of the right foot. Genetic evaluation confirmed an AKT1 mutation. Discussion: CLOVES syndrome, neurofibromatosis 1 or PTEN hamartoma tumor syndrome are partially superimposable entities to Proteus syndrome and may generate diagnostic doubt. Although the clinical criteria and histologic findings are indicative, the diagnostic confirmation of this entity is genetic.

Pharmacodynamic Study of Miransertib in Individuals with Proteus Syndrome

Proteus syndrome is a life-threatening segmental overgrowth syndrome caused by a mosaic gain-of-function AKT1 variant. There are no effective treatments for Proteus syndrome. Miransertib is an AKT1 inhibitor that, prior to this study, has been evaluated only in adult oncology trials. We designed a non-randomized, phase 0/1 pilot study of miransertib in adults and children with Proteus syndrome to identify an appropriate dosage starting point for a future efficacy trial using a pharmacodynamic endpoint. The primary endpoint was a 50% reduction in the tissue levels of AKT phosphorylation from biopsies in affected individuals. We also evaluated secondary efficacy endpoints. We found that a dose of 5mg/m2/day (1/7 the typical dose used in oncology) led to a 50% reduction in phosphorylated AKT (pAKT) in affected tissues from five of six individuals. This dose was well tolerated. Two of the six efficacy endpoints (secondary objectives) suggested that this agent may be efficacious. We observed a decrease in a cerebriform connective tissue nevus and a reduction in pain in children. We conclude that 5mg/m2/day of miransertib is an appropriate starting point for future efficacy trials and that this agent shows promise of therapeutic efficacy in children with Proteus syndrome.

Pathogenetic insights from quantification of the cerebriform connective tissue nevus in Proteus syndrome

The plantar cerebriform connective tissue nevus (CCTN) is the most common and problematic cutaneous manifestation of Proteus syndrome. To gain insights into CCTN pathogenesis and natural history. The size and location of plantar CCTN was measured on 152 images from 22 individuals with Proteus syndrome by 2 independent, blinded reviewers. Average measures of plantar CCTN were transformed into a linear mixed model to estimate proportionate change in size with age. Median patient age was 6.9years at study onset. The intraclass correlation coefficient between 2 blinded reviewers was 0.946 for CCTN single measures. The CCTN relative area increased with age in children (n=18, P<.0001) by 5.6% per year. Confluent papules and nodules extending beyond the boundaries of CCTNs were gradually replaced by typical CCTN over time. The location of CCTN in different individuals overlapped near the ball of the foot. A positive relationship between CCTN growth rate and AKT1 mutant allele frequency was observed (0.62, P=.10, n=8). This was a retrospective review using photographs. CCTN growth is affected by age and extent of the CCTN precursor lesion. Monitoring of CCTN size might prove useful for evaluating drug response in the treatment of Proteus syndrome.

266 Growth of the cerebriform connective tissue nevus in individuals with Proteus syndrome

266 Growth of the cerebriform connective tissue nevus in individuals with Proteus syndrome

Proteus Syndrome: Three Case Reports with a Review of the Literature

Proteus syndrome (PS) is a rare, progressive disorder that manifests as asymmetric, disproportionate overgrowth affecting tissues derived from any germline layer. Cases of PS from 2005–2010 were retrieved from the pathology files at our institution. Two confirmed cases and one possible case of PS were identified. All patients came from different ethnic backgrounds. Patient 1 displayed classic skin and overgrowth lesions. Patient 2 displayed various features, particularly vascular malformations. Patient 3 demonstrated a cerebriform connective tissue nevus alone. These patients demonstrate the spectrum of presentations of PS. Much is left to learn about this disfiguring disease.

Progressive overgrowth of the cerebriform connective tissue nevus in patients with Proteus syndrome

Proteus syndrome is a rare overgrowth disorder that almost always affects the skin. Our purpose was to evaluate progression of skin lesions in patients with Proteus syndrome. Skin findings were documented in 36 patients with Proteus syndrome. Progression of skin lesions in 16 of these patients was assessed by comparing photographs obtained on repeated visits for an average total duration of 53 months. The skin lesion most characteristic of Proteus syndrome, the cerebriform connective tissue nevus, showed progression in 13 children but not in 3 adults. The cerebriform connective tissue nevus progressed by expansion into previously uninvolved skin, increased thickness, and development of new lesions. Lipomas increased in size, number, or both in 8 of 10 children with lipomas. In contrast, epidermal nevi and vascular malformations generally did not spread or increase in number. Only 3 adults with Proteus syndrome were evaluated longitudinally. The cerebriform connective tissue nevus in Proteus syndrome grows throughout childhood but tends to remain stable in adulthood.

Monozygotic twins discordant for Proteus syndrome

Proteus syndrome is a rare, complex disorder predominantly characterized by asymmetric overgrowth of body parts, connective tissue and epidermal nevi, and vascular malformations. General diagnostic criteria comprise mosaic distribution, sporadic occurrence, and progressive course. We report on Proteus syndrome in discordant monozygotic twins. The affected 9-year-old boy showed progressive postnatal overgrowth of his right leg and foot and asymmetric progressive overgrowth of single toes with a small cerebriform connective tissue nevus on his right fourth toe. The progressive course was documented by serial photographs over a period of 3 years. Twin monozygosity was determined by PCR-amplified short tandem repeat (STR) analysis, revealing complete concordance of all alleles in both twins. This observation, to our knowledge, is only the second case report of discordant Proteus syndrome in monozygotic twins. This supports the hypothesis that this rare condition is caused by a postzygotic mutational event resulting in mosaicism.

A Mild Form of Proteus Syndrome

Proteus syndrome is a multisystem disorder and diagnosis has been difficult because of the variability of the syndrome's manifestations. Dermatologists have an important role as cutaneous findings could provide clues for the early diagnosis of the disease. Herein we report a case who had cerebriform connective tissue nevus and lipoma as the sole manifestations of the disease.

Proteus syndrome: An update

Proteus syndrome is a complex disorder consisting variably of disproportionate, asymmetric overgrowth of body parts; cerebriform connective tissue nevi; epidermal nevi; vascular malformations of the capillary, venous, and lymphatic types; and dysregulated adipose tissue. Serious complications may ensue, such as pulmonary embolism, cystic lung disease, and various neoplasms. Somatic mosaicism, lethal in the nonmosaic state, is the best working hypothesis. Although Proteus syndrome data are consistent with this hypothesis, it has not been proven. The etiology is unknown to date. Diagnostic criteria are emphasized because misdiagnosis of Proteus syndrome is common. Finally, evaluation and management are discussed.

Evolution of skin lesions in Proteus syndrome

Proteus syndrome is a rare overgrowth disorder that is generally progressive, but the natural history of the skin lesions is not known. Our purpose was to document the evolution of 4 common skin lesions in 16 patients with Proteus syndrome. Most epidermal nevi and vascular malformations were reported to appear in the first month of life and had little tendency for expansion or development of additional lesions. Subcutaneous lipomas and cerebriform connective tissue nevi were commonly noted in the first year of life, but not in the first month. Most patients reported that subcutaneous lipomas and cerebriform connective tissue nevi progressively increased in size, and in most patients additional lesions developed at new locations. Of the 4 types of skin lesions, plantar cerebriform connective tissue nevi were most frequently cited as a source of symptoms. Skin lesions of Proteus syndrome may not appear until later infancy or early childhood, making it difficult to diagnose in young children.