A case report of Proteus syndrome (PS).

BACKGROUND: Proteus syndrome (PS) is an extremely rare disease characterized by excessive chimeric growth of cells, and progressive and irregular asymmetrical hyperplasia. CASE PRESENTATION: Herein, a PS case with atypical clinical features and syndromes was reported, to improve the understanding of the diagnosis and treatment of the disease. The case was a 3-year-and-11-month-old male child. He was admitted due to a primary diagnosis of McCune-Albright syndrome. After admission, the lesion samples from the milk coffee spots, and nodular thickening skin at hands and feet were subjected to genetic screening. Genetic testing results confirmed the diagnosis of PS. CONCLUSIONS: Based on the clinical manifestations, laboratory tests, imaging data, and literature reviewing, the etiology, diagnosis, treatment and prognosis of PS have been analyzed and discussed.

Characterization of thrombosis in patients with Proteus syndrome.

Patients with overgrowth and complex vascular malformation syndromes, including Proteus syndrome have an increased risk of thromboembolism. Proteus syndrome is a mosaic, progressive overgrowth disorder involving vasculature, skin, and skeleton, and caused by a somatic activating mutation in AKT1. We conducted a comprehensive review of the medical histories and hematologic evaluations of 57 patients with Proteus syndrome to identify potential risk factors for thrombosis. We found that six of ten patients, who were deceased, died secondary to deep venous thrombosis and/or pulmonary embolism. Of the remaining 47 living patients, six had thromboembolic events that all occurred postoperatively and in an affected limb. Eleven of 21 patients had an abnormal hypercoagulable panel including Factor V Leiden heterozygotes, antithrombin III deficiency, positive lupus anticoagulant, or Protein C or S deficiencies. We observed that eight of 17 patients had an abnormal D-dimer level >0.5 mcg/dl, but deep venous thromboses occurred in only four of those with D-dimer >1.0 mcg/dl. We conclude that the predisposition to thrombosis is likely to be multifaceted with risk factors including vascular malformations, immobility, surgery, additional prothrombotic factors, and possible pathophysiologic effects of the somatic AKT1 mutation on platelet function or the vascular endothelium. The D-dimer test is useful as a screen for thromboembolism, although the screening threshold may need to be adjusted for patients with this disorder. We propose developing a registry to collect D-dimer and outcome data to facilitate adjustment of the D-dimer threshold for Proteus syndrome and related disorders, including PIK3CA-Related Overgrowth Spectrum.

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.

Clinical and historical aspects of the Elephant Man: exploring the facts and the myths.

Joseph Merrick, the Elephant Man, presented to the Royal London Hospital in 1884 with an obscure condition that puzzled his contemporaries, and fascinates clinicians to this day. Throughout the 1900s, a number of theories were advanced to explain the numerous growths that covered his body: neurofibromatosis, Proteus syndrome, and a combination of childhood injury, fibrous dysplasia, and pyarthrosis. The debate continued throughout the 20th century without resolution. Today, new consensus on the genetic and clinical diagnosis of neurofibromatosis and Proteus syndrome has allowed advancements in the Elephant Man's diagnosis. Using recent clinical diagnostic criteria it is now possible to conclude that Joseph Merrick was in all likelihood suffering from Proteus syndrome. Nevertheless, details of his genotype remain unknown. Obtaining intact DNA from the Elephant Man's skeleton is challenging, yet it is possible that sequencing Merrick's genome could provide genetic confirmation of his clinical diagnosis, and shed light on the process of tumourigenesis.

Proteus syndrome and hypothyroidism. An unusual association.

We present a case of a 3½-year-old girl diagnosed as Proteus syndrome with severe cosmetic disfigurement-macrodactyly, hemi-hypertrophy of the face and limbs, megalencephaly, lymph edema of both hands and feet along with severe global developmental delay. She was found to have severe recalcitrant epilepsy and also primary hypothyroidism; the association of which is not mentioned in the previous literature.

[Proteus syndrome with cerebral vascular malformations]. / Síndrome de Proteus con malformaciones vasculares cerebrales.

INTRODUCTION: Proteus syndrome is a congenital hamartomatous dysplasia. This sporadic disorder involves the skeletal system, soft tissues, skin and vascular system. The most likely pathogenesis involves somatic mosaicism. Main manifestations included soft-tissue and epidermal nevi, partial gigantism, hemihypertrophy, exostoses, lipomas and vascular anomalies. The most common brain abnormalities are hemimegencephaly and migrational disorders. We present a case of Proteus syndrome with cerebral vascular anomalies which are not described previously. CLINICAL CASE: Our patient is a 61 year-old male who has hypertrophy of the four limbs, macrodactyly and hypertrophy of chest and abdomen asymmetric with mild facial asymmetry. Prominent and abundant of the four extremities and trunk, also asymmetric. Vascular tumors in the skin of trunk and left limb. Cerebral MRI shows venous angiomas and multiple cavernous malformations. CONCLUSION: Clinical diagnostic criteria of Proteus syndrome are documented in our patient. He also has brain vascular malformations which are not described previously in the literature. We consider that both findings are not a product of causality due to the high prevalence of systemic vascular hamartomatous malformations in these patients. We hypothesize that a single mutation, probably involving genes in relation with apoptotic control will be responsible of Proteus syndrome and cerebral vascular anomalies in our patient, due to a defect of angiogenesis.

Síndrome de Proteus con malformaciones vasculares cerebrales / Proteus syndrome with cerebral vascular malformations

Introducción. El sindrome de Proteus es una displasia hamartomatosa congénita y esporádica que afecta a huesos, tejido conectivo, piel y sistema vascular. Se atribuye a un mosaicismo somático del que se desconoce el gen responsable. Los signos principales incluyen nevo del tejido conjuntivo y epidérmico, gigantismo parcial, hemihipertrofia corporal, exostosis, lipomas y anomalías vasculares. Las alteraciones cerebrales más frecuentemente descritas son la hemimegaencefalia y las alteraciones de la migración. Presentamos un caso de síndrome de Proteus con alteraciones cerebrales vasculares no descritas previamente. Caso clínico. Nuestro paciente es un varón de 61 años que presenta hipertrofia de las cuatro extremidades con macrodactilia junto con hipertrofias de tórax y abdomen asimétricas, así como ligera asimetría facial. Prominentes y abundantes venas varicosas en las cuatro extremidades y tronco, de forma asimétrica. Lesiones cutáneas vasculares en costado y pierna izquierda. En angio-RM cerebral se observan imágenes muy sugerentes de angiomas venosos y angiomas cavernosos múltiples. Conclusiones. Nuestro paciente cumple criterios clínicos para el diagnóstico de síndrome de Proteus; además presenta alteraciones venosas cerebrales en forma de angiomas venosos y cavernomas múltiples. Dichas alteraciones cerebrales no han sido descritas con anterioridad en relación a este síndrome. Consideramos que ambos hallazgos no son producto de la casualidad dada la alta prevalencia de malformaciones hamartomatosas vasculares a nivel sistémico en estos pacientes. Postulamos que una misma mutación, probablemente implicando genes relacionados con el control de la apoptosis, sería la causa del síndrome de Proteus y de la cavernomatosis y angiomatosis venosa cerebral de nuestro paciente debido a un defecto extendido de la angiogénesis

Introduction. Proteus syndrome is a congenital hamartomatous dysplasia. This sporadic disorder involves the skeletal system, soft tissues, skin and vascular system. The most likely pathogenesis involves somatic mosaicism. Main manifestations included soft-tissue and epidermal nevi, partial gigantism, hemihypertrophy, exostoses, lipomas and vascular anomalies. Ihe most common brain abnormalities are hemimegencephaly and migrational disorders. We present a case of Proteus syndrome with cerebral vascular anomalies which are not described previously. Clinical case. Our patient is a 61 year -old male who has hypertrophy of the four limbs, macrodactyly and hypertrophy of chest and abdomen asymmetric with mild facial asymmetry. Prominent and abundant of the four extremities and trunk, also asymmetric. Vascular tumors in the skin of trunk and left limbo Cerebral MRI shows venous angiomas and multiple cavernous malformations. Conclusion. Clinical diagnostic criteria of Proteus syndrome are documented in our patient. He also has brain vascular malformations which are not described previously in the literature. We consider that both findings are not a product of causality due to the high prevalence of systemic vascular hamartomatous malformations in these patients. We hypothesize that a single mutation, probably involving genes in relation with apoptotic control will be responsible of Proteus syndrome and cerebral vascular anomalies in our patient, due to a defect of angiogenesis

Proteus syndrome: a natural clinical course of Proteus syndrome.

A 16-year-old Korean male patient presented with macrodactyly, hemihypertrophy of the face and extremities, plantar cerebriform hyperplasia, a subcutaneous mass of the left chest, macrocephaly and verrucous epidermal nevi. These findings are consistent with Proteus Syndrome. The clinical features, etiology, management, natural course and differential diagnosis of this case are discussed.

The multifaceted challenges of Proteus syndrome.

Proteus syndrome is a rare and sporadic disorder that causes postnatal overgrowth of multiple tissues in a mosaic pattern. The overgrowth can involve skin, subcutaneous tissue, connective tissue (including bone), the central nervous system, and viscera. Complications of Proteus syndrome include, among others, progressive skeletal deformities, invasive lipomas, benign and malignant tumors, and deep venous thrombosis with pulmonary embolism. Care of patients with Proteus syndrome presents significant challenges to both physicians and parents because of the various medical as well as psychosocial consequences of the disease. Herein, the case of a 5-year-old patient who manifested a number of these complications is presented. Current knowledge about the diagnosis, natural history, etiology, and management of the disorder is reviewed.

[Neurophysiological aspects of Proteus syndrome]. / Aspectos neurofisiológicos en el síndrome de Proteus.

INTRODUCTION: The Proteus Syndrome was defined in 1983 by Wiedeman. However, the first case mentioned in the literature was that of Joseph Merrick, the Elephant Man, presented by Sir Frederick Treves in 1884. It is a rare pathological condition. Its multiple clinical features include; partial gigantism of hands and/or feet, pigmented nevi, hemihypertrophy of the body, tumors, skeletal anomalies, growth disorders and visceral anomalies. Hereditary transmission has not been clearly defined. Diagnosis and treatment require the participation of experts from several medical and surgical specialties. CLINICAL CASE: We present a case sent to our hospital for the surgical correction of cranio-facial malformations. Epileptic crises post-operatively indicated the need for neurological and neuro-physiological study. This was done by means of conventional electro-encephalography: brainstem, somato-sensorial and visual auditory evoked potentials, together with imaging techniques which showed the structural and functional asymmetry of the central nervous system at both cerebral and brainstem levels. CONCLUSIONS: Few neuro-physiological studies are included in the literature we reviewed for this paper. Therefore we do not know whether the functional anomalies of the central nervous system which we describe should be considered to be part of the syndrome.

Síndrome de Proteus / Proteus syndrome

Introducción. Wiedemann describió en 1983 por primera vez el síndrome de Proteus en toda su extensión. Consiste en una gran variedad de síntomas, todos caracterizados por sobrecrecimiento focal: macrodactilia, gigantismo (parcial) de manos/pies, con dermatoglifos cerebriformes característicos de palmas y plantas, hemihipertrofia, tumores subcutáneos (linfangiomas y lipomas), nevos pigmentados y macro-encefalia focal entre otros. El síndrome también es pleomorfo en el tiempo. Casos clínicos. Caso 1. Femenino de 14 meses con seguimiento de dos años. A su nacimiento se observó aumento de volumen de manos y pies, hemihipertrofia corporal izquierda y máculas eritematosas difusas. Se observó un aumento progresivo de tejido subcutáneo en extremidades, macrodactilia y la aparición de los dermatoglifos. Las radiografías confirman la hipertrofia tanto en tejidos blandos como de huesos largos y de metacarpianos/tarcianos. La tomografia computada muestra hemi-macroencefalia. Existe encefalopatía difusa en el electroencefalograma. La biopsia muestra un nuevo hamartomatoso. Evoluciona con leve retraso mental. Caso 2: femenino de quince meses con hemihipertrofia corporal derecha y macrodactilia, sin alteraciones vasculares todavía. Conclusiones. La patogenia del síndrome probablemente consiste en una mutación somática, en un gen que regula la cantidad y la afinidad de los receptores del factor de crecimiento tipo insulina II (insulin-like growth factor II binding protein). Todavía es un síndrome poco conocido y probablemente subdiagnosticado, que tiene que formar parte del diagnóstico diferencial en cualquier niño con hipertrofias focales. Aún si el paciente al primer contacto no tiene todos los signos, el seguimiento es primordial

The radiological features of hemimegalencephaly including three cases associated with proteus syndrome.

We report the radiological appearances of 5 children with hemimegalencephaly. There are few reports of this rare condition in the radiological literature. Two of the children have hemimegalencephaly as an isolated finding while the other three have Proteus syndrome. Four children have seizures which commenced within the first 6 months of life and two of these subsequently required hemispherectomy. In addition to the typical radiological features of hemimegalencephaly there was a high incidence of other brain anomalies. These include hypoplasia of the corpus callosum and crus cerebri, grey and white matter calcification and cortical migration/organisational disorders.

Growth hormone (GH), insulin-like growth factors (IGFs), and IGF-binding protein-3 (IGFBP-3) in a child with Proteus syndrome.

Proteus syndrome is a congenital hamartomatous disorder characterized by partial overgrowth involving all germ layers. A somatic mutation model has been proposed since familial cases are extremely rare. We report on a 3-year-old girl with typical manifestations of Proteus syndrome, including local, asymmetric hypertrophy of various parts of the body. Total body length was reduced. Serum levels of IGF-I and especially IGF-II and their major growth hormone dependent binding protein (IGFBP-3) were significantly reduced, although growth hormone secretion after a pharmacological stimulus was normal. In vitro studies of fibroblasts derived from hypertrophied tissue showed normal IGF-I production and somewhat reduced IGF-II and IGFBP-3 production as compared to normal human skin fibroblasts. Affinity cross-linking experiments showed that fibroblasts of the affect tissue in Proteus syndrome produced an unusual pattern of IGF bindings proteins containing large amounts of an IGFBP with high affinity to IGF-II. The data suggest that IGF production is generally disturbed in Proteus syndrome with imbalanced levels of specific IGFBP in affected tissue.

Proteus syndrome with cardiomyopathy and a myocardial mass.

Proteus syndrome is an overgrowth syndrome principally affecting cutaneous and skeletal tissues, accompanied by subcutaneous hamartomas. We report on a patient with predominantly skeletal and visceral involvement, including a cardiac mass and thickening of the myocardial septum affecting cardiac conduction and contraction.