Congenital Plaque-Type Glomuvenous Malformations Presenting in Childhood

Abstract

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, redpink 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.

Genotypes and Phenotypes of 162 Families with a <b><i>Glomulin</i></b> Mutation

“…The most frequent unusual presentation was a plaque-like GVM, which can be confused with a capillary malformation. We reported 10 such cases earlier, 3 of which had a proven GLMN mutation [Mallory et al, 2006]. Nine additional plaque-like GVMs were detected in this series.…”

“…A mutation was found in 60 GVM, 9 VM and none of the BRBN samples. Taking into account the 87 families that we reported previously [Brouillard et al, 2002[Brouillard et al, , 2005[Brouillard et al, , 2008Mallory et al, 2006;Goujon et al, 2011;Butler et al, 2012] ac.be/vikkula/VAdb/). The majority (143/162; 88%) of the patients in which a mutation was found had a familial history of the disorder; only 19 patients were considered sporadic.…”

“…1 F-H) [Boon et al, 2004]. Diagnosis can also be confounded with a capillary malformation and a plaque-like GVM [Mallory et al, 2006]. Several clinical criteria and a biomarker have been defined [Dompmartin et al, 2010].…”

“…Plaque-like GVM, which is less frequent, is flat and purple in the newborn but darkens with time ( fig. 1 A, individual 810) [Mallory et al, 2006]. Most are located on the extremities.…”

“…We mapped the VMGLOM locus on the short arm of chromosome 1, in 1p21p22 [Boon et al, 1999;Brouillard et al, 2000;Irrthum et al, 2001], and identified the causative gene that we named glomulin ( GLMN ) [Brouillard et al, 2002]. We have reported a GLMN mutation in 87 families [Brouillard et al, 2002[Brouillard et al, , 2005[Brouillard et al, , 2008Mallory et al, 2006;Goujon et al, 2011;Butler et al, 2012], and others reported 6 [O'Hagan et al, 2006;Ostberg et al, 2007;Borroni et al, 2011]. The mutations result in loss of function, either by causing a stop codon, by altering the reading frame or by changing the splice-site consensus sequences, leading to aberrant transcripts.…”