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Glomuvenous malformations (GVMs) are hereditary vascular malformations characterized by the presence of small, multifocal bluish-purple venous lesions involving the skin.
ORPHA:83454Classification level: Disorder
- Hereditary multiple glomangiomas
- Multiple glomus tumors
- Venous malformations with glomus cells
- Prevalence: Unknown
- Inheritance: Autosomal dominant
- Age of onset: Infancy, Childhood, Adolescent, Adult, Neonatal
- ICD-10: Q27.8
- OMIM: 138000
- UMLS: C1841984
- MeSH: C536827
- GARD: -
- MedDRA: 10018381
Prevalence is unknown; about 100 families have been reported in the literature so far.
GVMs may be present at birth, and slowly expand during childhood. New small lesions appear with time. They are usually hyperkeratotic, raised and nodular with a cobblestone surface. Color varies from pink to purplish-dark blue. However, in some cases (especially in newborns) the lesions may be flat and purple in color; this plaque-like GVM usually darkens with time. GVMs are often painful on palpation and cannot be completely emptied by compression. They are usually multifocal and are located mainly on the extremities, involving the skin and subcutis. They are rarely encountered in mucosae and intestinal hemorrhage is not a feature of this condition. There is significant clinical variation with respect to the size, location and number of lesions, even between affected individuals from the same family. Patients with GVMs have normal mental and physical development.
GVMs are caused by mutations in the gene encoding glomulin (GLMN; 1p22.1). Paradominant inheritance was suggested by the identification of a double-hit mutation in one lesion, indicating that GVM lesions may be due to complete localized loss of glomulin. Glomulin is specifically expressed in vascular smooth muscle cells (vSMCs), but its exact function remains unknown.
Diagnosis of GVM is based on clinical evaluation of the cutaneous lesions. Doppler ultrasound examination and MRI can be used to confirm the venous component and extent of the lesions. Histologically, GVMs are characterized by the presence of abnormal mural cells called ``glomus cells''. Molecular genetic testing for confirmation of the diagnosis is available on a research basis.
The differential diagnosis should include mucocutaneous venous malformations (VMCMs, which are also commonly seen on mucosal membranes, are lighter purple in color than GMVs, and are compressible and generally not painful on palpation; see this term) and Blue rubber bleb nevus syndrome (characterized by the association of cutaneous and mucosal venous-like lesions with gastrointestinal lesions; see this term).
Prenatal diagnosis is feasible for affected families in which the disease-causing mutation has been identified, but is not widely available.
GVMs are inherited in an autosomal dominant manner. Genetic counseling should be provided for affected families, informing patients of a 50% risk of inheriting the disease-causing mutation and of the variability in clinical expression.
Management and treatment
The most effective treatment is plastic and reconstructive surgery, used depending on the size and location of the lesions. Sclerotherapy may be indicated in some cases: the sclerosing agent ethanol (96%) in the form of a gel for injection obtained EU orphan drug designation in April 2005 for the treatment of congenital venous malformations.
The prognosis for patients is good, malignant transformation has not been reported and the life expectancy for patients is not reduced.