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. Mutations in the glomulin gene were found in those patients who participated in the genetic study. CONCLUSIONS: Congenital plaque-type GVMs are unique in their congenital nature, extensive distribution, difficult to diagnose and treat, and progressive involvement after birth. Most cases are familial, yet affected relatives usually have only minor lesions. The lesions of congenital plaque-type GVM are severe, visible at birth, and usually mistaken for extensive venous malformations. Vascular malformations are divided by hemodynamic type into slow-flow and fast-flow lesions. Slow-flow lesions are subcategorized as capillary, lymphatic, and venous.(1) Capillary malformations are flat, sharply demarcated, red-pink vascular stains of the skin commonly referred to as port-wine stains. These persist throughout life and are characterized histologically by dilated capillaries within the dermis. They slowly increase in size with age. Lymphatic malformations are spongelike collections of abnormal channels and spaces that contain clear lymphatic fluid, causing an excess of fluid to accumulate and dilate the lymphatic channels. This results in swelling of the affected area and, if extensive, can cause enlargement of soft tissues and bones.     

Mutation analysis in Irish families with glomuvenous malformations

BACKGROUND: Glomuvenous malformations (GVMs) are rare bluish lesions that can affect the skin and mucosal surfaces. They represent defects in vasculogenesis. Lesions can occur sporadically or in an autosomal dominant mode of inheritance. Recent studies have shown that mutations in the glomulin gene (GLMN) on chromosome 1p21-22 are responsible for familial GVMs. OBJECTIVES: To search for mutations in GLMN in Irish families with GVMs. METHODS: We identified four Irish families with GVMs and confirmed linkage to chromosome 1p21-22 in these cases. We sequenced the glomulin gene in all affected and unaffected members of the families. Results Linkage analysis showed that affected individuals from the families shared a common haplotype. Mutation analysis revealed a delAAGAA mutation in exon 3 of the glomulin gene in all four families with GVMs. CONCLUSIONS: We confirm that mutations in the glomulin gene are responsible for GVMs and suggest a founder Irish mutation in the glomulin gene in four Irish families.     

Genetic analysis of a family with hereditary glomuvenous malformations

Glomuvenous malformations (MIM 138000) are rare vascular malformations consisting of glomus cells, and in affected individuals, lesions may appear in any number anywhere on the body. We analysed the DNA of one family with hereditary glomuvenous malformations and identified the mutation causing the disease in the glomulin gene on chromosome 1 p22. The deletion started at base pair 157: 157delAAGAA, which is a deletion of five base pairs. This mutation has been found in Europe, the USA and Australia, suggesting a founder effect with common ancestry. Thus far, no second-hit mutation for the 157delAAGAA mutation has been identified.     

Congenital plaque-type glomuvenous malformations associated with fetal pleural effusion and ascites

Glomuvenous malformations are hereditary vascular anomalies, usually without extracutaneous involvement. We report two cases of extensive thoracic plaque-type glomuvenous malformation in newborns who had previously been diagnosed in utero with pleural effusion and ascites, suggesting a pathogenic link between the two conditions.     

A novel mutation of the glomulin gene in an Italian family with autosomal dominant cutaneous glomuvenous malformations

Glomuvenous malformations (GVM) are hamartomas characterized histologically by glomus cells, which should be distinguished from glomus tumors. Familial GVM are rare, often present as multiple lesions, and exhibit familial aggregation, with autosomal dominant transmission. GVM are caused by mutations of the glomulin (GLMN) gene on chromosome 1p21-p22. Their development is thought to follow the 'two-hit' hypothesis, with a somatic mutation required in addition to the inherited germline mutation. We describe a novel GLMN mutation in an Italian family with GVM in which some members present with the less commonly observed phenotype of solitary lesions. A second somatic 'hit' mutation in GLMN was not discovered in our family. We further provide histological, immunohistochemical and electron microscopic data exhibiting the classic features of GVM. The diagnosis of GVM is critical because of distinction from venous malformations and blue rubber bleb nevus syndrome, which may demonstrate clinical similarities but require different treatment.     

A collection of rare anomalies: multiple digital glomuvenous malformations,epidermal naevus,temporal alopecia,heterochromia and abdominal lipoblastoma

Glomuvenous malformations are a subtype of venous malformations, which present in infancy or childhood. We describe a teenage girl who presented with multiple digital glomuvenous malformations from birth. In addition, she had an epidermal naevus on the upper lip, an area of congenital alopecia of the scalp, heterochromia irides and an abdominal lipoblastoma. We are unaware of any reports of the association of multiple glomuvenous malformations with the other uncommon developmental anomalies seen in our patient, and a common link eludes us.     

Incomplete penetrance of GLMN gene c.395–1G>C mutation in a family with glomuvenous malformations

Glomuvenous malformations (GVMs, OMIM 138000) are hamartomas presenting in childhood as multiple, bluish, soft papules and nodules that tend to grow slowly in size and number with age. They are caused by autosomal dominant mutations in glomulin (GLMN) gene; penetrance varies from 80% at 20 to about 100% at age 30 years. We report on the c.395–1G>C mutation of GLMN gene in two siblings showing variable penetrance.     

Congenital plaque-type glomuvenous malformation associated with chylous ascites

Congenital plaque-type glomuvenous malformation (GVM) is caused by loss of function mutations in glomulin gene. We report a newborn with this rare vascular disorder associated with chylous ascites. The common mesenchymal origin of GVM and lymphatic vessels as well as the glomulin expression in vascular smooth muscle cells in utero could help explain this unusual prenatal complication of glomuvenous malformations.     

Large plaque-like glomuvenous malformation (glomangioma) simulating venous malformation

Glomuvenous malformations and venous malformations are vascular lesions that can be distinguished on the basis of clinical and pathological features. A vascular lesion of the skin and superficial and deep soft tissues of a lower limb in a 5-year-old child is described. The clinical and radiological features, including skeletal muscle involvement, were typical of venous malformation, whereas the histopathological features were those of a glomuvenous malformation. The clinical and histopathological features are briefly discussed.     

Glomuvenous malformations

A 9-year-old girl presented with a congenital, blue-purple, partially compressible plaque with a cobblestone surface on the left lateral foot and ankle. Similar, solitary, blue nodules later appeared elsewhere on the extremities. The lesions were tender to palpation and were associated with spontaneous paroxysms of pain and paresthesias. Histopathologic evaluation of a skin biopsy specimen showed rows of glomus cells that surrounded thin-walled vascular channels, which confirmed the diagnosis of glomuvenous malformations. This autosomal dominant condition, which is due to mutations in the GLMN gene, presents with clinical findings that are distinct from those of familial, multiple, cutaneous and mucosal venous malformations. Treatment options include excision, sclerotherapy, and laser therapy (ablative or pulsed dye).     

Unilateral linear capillaritis

We present four cases of a distinctive type of pigmented purpuric eruption occurring in a striking linear and pseudo-dermatomal distribution in young males. Whilst these cases share some of the clinical and histological features of other pigmented purpuric dermatoses, they are not readily classified with any of the entities so far defined in this group of disorders. We believe these cases represent a distinct group not previously described. Four patients with an unusual pigmented purpuric eruption are presented.     

Unilateral darier's disease

Various variations of Darier's disease have been mentioned in the literature. Here we describe a young male with unilateral involvement with clinical and histopathological features typical of Darier's disease.     

Unilateral lichen planus

A case of lichen planus with unilateral distribution of lesions is reported in a 26-year-old woman. The patient had no associated neurologic signs or symptoms. The role of neurologic influences in lichen planus is stressed.     

Unilateral nevoid telangiectasia

Unilateral nevoid telangiectasia is a cutaneous condition consisting of congenital or acquired patches of superficial telangiectases in a unilateral linear distribution. Unilateral nevoid telangiectasia has been associated with elevations of blood estrogen levels and/or an increased number of estrogen receptors in the involved skin. We present a hepatitis-B carrier case with unilateral nevoid telangiectasia on the face and the right side of the neck; she had normal blood estrogen and a normal number of estrogen receptors in the involved skin.     

Unilateral blepharochalasis.

True blepharochalasis occurring in young adults and associated with recurrent bouts of eyelid swelling and eventual lid laxity is an uncommon entity. We report the case of an 18-year-old woman who had a nine-year history of unilateral blepharochalasis. A skin biopsy specimen that showed the absence of stainable elastic tissue confirmed the clinical impression, and appropriate surgical correction was carried out.