Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations.

Blue rubber bleb nevus syndrome (Bean syndrome) is a rare, severe disorder of unknown cause, characterized by numerous cutaneous and internal venous malformations; gastrointestinal lesions are pathognomonic. We discovered somatic mutations in TEK, the gene encoding TIE2, in 15 of 17 individuals with blue rubber bleb nevus syndrome. Somatic mutations were also identified in five of six individuals with sporadically occurring multifocal venous malformations.

Common somatic alterations identified in maffucci syndrome by molecular karyotyping.

Maffucci syndrome (MS) is a rare congenital disorder characterized by multiple central cartilaginous tumors (enchondromas) in association with cutaneous spindle cell hemangiomas. These patients have a high incidence of malignant transformation. No familial case is known and the etiopathogenic cause remains unknown.

Somatic uniparental isodisomy explains multifocality of glomuvenous malformations.

Inherited vascular malformations are commonly autosomal dominantly inherited with high, but incomplete, penetrance; they often present as multiple lesions. We hypothesized that Knudson's two-hit model could explain this multifocality and partial penetrance. We performed a systematic analysis of inherited glomuvenous malformations (GVMs) by using multiple approaches, including a sensitive allele-specific pairwise SNP-chip method.

[Osteoma cutis presenting as an erythematous and grainy, retroauricular plaque].

Background: Authentic bone tissue can be observed in the skin, in both the epidermis and dermis, where it produces cutaneous osteomas. These lesions are classed as either primary or secondary ossifications. Secondary ossifications are the consequence of inflammatory lesions such as acne or injuries while primary ossifications are neither preceded by preexisting lesions nor associated with other lesions.

[Classification of superficial vascular anomalies].

All superficial vascular abnormalities are not angiomas even though this term continues - incorrectly - to be used. Because the suffix "oma" implies a tumor, it is necessary to differentiate true vascular tumors, such as infantile hemangioma, from vascular malformations. From a hemodynamic perspective, there are two types of vascular malformations: slow- and fast-flow.

Hereditary cutaneomucosal venous malformations are caused by TIE2 mutations with widely variable hyper-phosphorylating effects.

Mutations in the angiopoietin receptor TIE2/TEK have been identified as the cause for autosomal dominantly inherited cutaneomucosal venous malformation (VMCM). Thus far, two specific germline substitutions (R849W and Y897S), located in the kinase domain of TIE2, have been reported in five families. The mutations result in a fourfold increase in ligand-independent phosphorylation of the receptor.

Nasal tip haemangiomas: guidelines for an early surgical approach.

The treatment of Cyrano nose haemangioma (CNH) is difficult because of its location and possible complications: psychological impact, severe skin infiltration and consequences on nasal growth. We suggest that the best treatment for nasal tip haemangiomas is an early surgery to remove the affected tissues and preserve the anatomy. A total of 39 children (32 females and seven males) underwent early surgery for the treatment of CNH.

Role of Propranolol in the therapeutic strategy of infantile laryngotracheal hemangioma.

There are recent reports of effective treatment of cutaneous hemangiomas with Propranolol. The current study aims to assess efficacy of systemic Propranolol for subglottic hemangiomas and to discuss its place among the other available therapies. We report 2 infants with subglottic hemangiomas, which were resistant to other established medical treatments.

Frequency and phenotypes of cutaneous vascular malformations in a consecutive series of 417 patients with familial cerebral cavernous malformations.

Background: Familial cerebral cavernous malformations (FCCM) are vascular malformations inherited as an autosomal-dominant condition. Three genes (KRIT1/CCM1, MGC4607/CCM2, PDCD10/CCM3) have been identified so far. Extra-neurological manifestations include retinal and cutaneous vascular malformations.

Coagulation disorders in patients with venous malformation of the limbs and trunk: a case series of 118 patients.

Objective: To investigate the clinical characteristics of venous malformation of the limbs and trunk and known but poorly appraised associated coagulation disorders. Venous malformations are ubiquitous, slow-flow vascular anomalies known to be occasionally painful because of thrombotic episodes inside the lesion.

Design: Large case series, with screening of accepted standard coagulation tests.

Utility of radiofrequency ablation for haemorrhagic lingual lymphangioma.

Lymphangiomas of the mouth and tongue pose considerable therapeutic problems. Their complete exeresis is not feasible, and they can be a major functional impediment and cause face and jaw deformities. A risk of secondary growth is classically described after surgical reduction.

Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast-flow vascular anomalies are caused by RASA1 mutations.

Capillary malformation-arteriovenous malformation (CM-AVM) is a newly recognized autosomal dominant disorder, caused by mutations in the RASA1 gene in six families. Here we report 42 novel RASA1 mutations and the associated phenotype in 44 families. The penetrance and de novo occurrence were high.

Prenatal imaging findings in rapidly involuting congenital hemangioma of the skull.

We report two cases of rapidly involuting congenital hemangioma (RICH) of the skull diagnosed in the third trimester of gestation, and also present a brief review of the literature. In both of our cases ultrasound examination showed a soft tissue vascular mass of the skull with a specific sonographic finding: a thin hyperechogenic line over the lesion and continuous with the calvaria, suggesting a subperiosteal origin and possibly accounting for a mass effect on the underlying skull. This was slight in one case and marked in the other (and associated with involvement of the calvaria).

Uncommon benign infantile vascular tumors.

Significant progress in the diagnosis of infantile vascular tumors has been achieved during the past 2 decades because of improvements in the recognition of clinical characteristics, radiologic features, and histopathologic analysis, as well as the discovery of important immunophenotypic markers such as GLUT-1. These recent advances make it possible to define more clearly the distinct clinical entities with their variable prognoses and to improve the management of lesions that, although histologically benign, infrequently may be lethal because of their invasive potential.

Use of ultrasonic dissection in the early surgical management of periorbital haemangiomas.

Purpose: To evaluate the efficacy and safety of the early surgical excision of periorbital haemangiomas with an ultrasonic scalpel in infants at risk of visual impairment.

Study: A retrospective analysis of 67 infants diagnosed to be at risk of amblyopia from periorbital haemangiomas, treated consecutively with the Dissectron between 1994 and 2005. Ophthalmic outcome parameters included the pre- and postoperative measurement of visual axis occlusion, strabismus, astigmatism, and degree of amblyopia.

Endothelial cells in infantile haemangiomas originate from the child and not from the mother (a fluorescence in situ hybridization-based study).

Background: Infantile haemangiomas are benign vascular tumours of infancy of unknown origin. Their aetiological relationship to maternal cells has been questioned given that they develop during the neonatal period.

Objectives: As endothelial cells in the placenta may be of maternal or fetal origin, we questioned whether vascular haemangioma cells originated from fetal or maternal tissue.

Vascular malformations. Part II: associated syndromes.

Unlabelled: Cutaneous vascular malformations are rare disorders representing errors in vascular development. These lesions occur much less commonly but are often confused with the common infantile hemangioma. It is important to properly diagnose vascular malformations because of their distinct differences in morbidity, prognosis and treatment.

[Antenatal diagnosis of rapidly involuting congenital hemangiomas (RICH)].

Introduction: Since 1996, vascular anomalies are classified either as tumors or malformations. Infantile hemangioma is the most common vascular tumor. It is an endothelial cellular proliferation, stimulated after birth (10th day) which then slow involves.

Vascular malformations: Part I.

Unlabelled: Cutaneous vascular malformations are rare disorders representing errors in vascular development. These lesions occur much less commonly but are often confused with the common infantile hemangioma. It is important to properly diagnose vascular malformations because of their distinct differences in morbidity, prognosis and treatment.

Successful management of a retroperitoneal kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon using alpha-interferon.

It has been shown recently that Kasabach-Merritt phenomenon, the association of a vascular tumour and consumption coagulopathy, does not--as previously thought--complicate "classical" infantile hemangiomas but distinctive entities called kaposiform hemangioendothelioma (KHE) and tufted angioma (TA), both tumours on the same neoplastic spectrum. These tumours have been found in the neck, face, thorax, abdomen, retroperitoneum and limbs and are associated with a mortality rate of as high as 30 %. Several therapeutic modalities, including alpha-interferon, vincristine, radiotherapy and surgery have been reported in the literature.

[Congenital haemangiomas and other rare infantile vascular tumours].

A number of infantile tumours, far less frequent than infantile haemangiomas, were long assimilated to them. Today they are clearly individualised, based on distinctive clinical and pathologic features, and this difference has been supported by the discovery of new immunophenotypic markers such as GLUT1. GLUT1 stains 100% of infantile haemangiomas and none of the other infantile vascular tumours.

Congenital plaque-type glomuvenous malformations presenting in childhood.

Background: Glomuvenous malformations (GVMs) are now considered a separate entity from venous malformations. The rarest type of GVM is the generalized congenital plaque-type GVM.

Observations: We present 10 new cases of congenital plaque-type GVM and describe their clinical progression and treatment.