Symptomatic Congenital Hemangioma and Congenital Hemangiomatosis Associated With a Somatic Activating Mutation in <i>GNA11</i>

Funk, Tracy; Lim, Young Hee; Kulungowski, Ann M.; Prok, Lori; Crombleholme, Timothy M.; Choate, Keith; Bruckner, Anna L.

doi:10.1001/jamadermatol.2016.2365

Cited by 36 publications

(34 citation statements)

References 10 publications

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“…It has been proposed that a multifocal phenotype can result from these somatic mutations occurring early in embryologic development. The cutaneous lesions of our two cases are remarkably similar to the multifocal lesions reported by Funk et al …”

Section: Discussionsupporting

confidence: 90%

“…Typically occurring as solitary and large tumors of the skin or liver, congenital hemangiomas are often diagnosed clinically or by radiologic imaging. Histologically, they are distinguished from infantile hemangiomas by a unique vascular architecture and lack of immunostaining for the glucose transporter‐1 (GLUT‐1) protein . Congenital hemangiomas are characterized by widely dilated vessels with prominent intra‐ and perilobular channels with minimally prominent endothelium .…”

Section: Discussionmentioning

confidence: 99%

“…Typically round to oval in shape and red in color, CH is most often solitary and have a predilection for the head or limbs near a joint . Three clinical subtypes are recognized and classified based on their postnatal behavior: rapidly involuting (RICH), non‐involuting (NICH), and partially involuting . It is now believed that these lesions represent a spectrum of disease.…”

Section: Introductionmentioning

confidence: 99%

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Multifocal congenital hemangioma: Expanding the pathogenesis of “neonatal hemangiomatosis”

Blumenthal

Stefanko

Cossio

et al. 2019

Pediatric Dermatology

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Congenital hemangiomas are benign vascular tumors, categorized by their postnatal behavior as rapidly involuting, non‐involuting, or partially involuting. They are typically solitary, with a predilection for the head or limbs near a joint. We present two infants with small, multifocal congenital nonprogressive hemangiomas of the skin, one associated with hepatic and intracranial lesions, and another with an in utero intracranial hemorrhage and hydrocephalus. These cases further extend the differential diagnosis of congenital multifocal vascular lesions or “hemangiomatosis.”

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Multifocal congenital hemangioma: Expanding the pathogenesis of “neonatal hemangiomatosis”

Blumenthal

Stefanko

Cossio

et al. 2019

Pediatric Dermatology

View full text Add to dashboard Cite

show abstract

“…In a case described by Funk et al, a large vascular tumor and innumerable smaller vascular tumors were present at birth, and more vascular tumors developed postnatally. Tissue genomics showed a mutation in GNA11, confirming diagnosis of multifocal CH . This same mutation is seen in several other conditions, including blue nevi and uveal melanomas .…”

Section: Discussionsupporting

confidence: 52%

Atypical presentations of congenital hemangiomas: Extending the clinical phenotype

West

Totoraitis

Yadav

et al. 2019

Pediatric Dermatology

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Background/Objectives Congenital hemangiomas (CH) are a group of benign vascular tumors that are present at birth and exhibit variable involution during infancy. Congenital hemangiomas that do not involute are typically solitary patch or plaque‐type tumors that grow proportionally with somatic growth. We report a case series of 9 patients with persistent CH, which exhibited uncommon features including segmental involvement, recurrent or severe pain, or growth via volumetric increase in size or apparent increased extent of anatomic involvement over time. Methods Via retrospective chart review, we included patients with persistent CH and atypical presentations. Available data regarding clinical characteristics, natural history, histopathology, imaging, and genetic tests were collected. Results Data on 9 patients were collected, including 7 noninvoluting CH and 2 partially involuting CH. Three of the 9 cases had segmental distribution, 6 had apparent growth or clinical evolution, and 4 were symptomatic with pain. One also had marked localized intravascular coagulopathy. Conclusions Ongoing or recurrent pain and large extent of anatomic involvement can be features of CH, albeit uncommon ones, and can pose both diagnostic and management challenges. Tissue genomic studies can offer a novel tool for CH diagnosis.

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“…Our identification of GNA14 mutations in KHEs, TAs, and LCHs-three distinct classes of vascular tumors-also highlights the pleiotropy of G aq variants, as seen in GNAQ and GNA11 mutations causing LCHs, PWSs, and NICHs. [10][11][12]16,19 Similarly, activating mutations in HRAS, KRAS, and NRAS also demonstrate phenotypic heterogeneity within vascular anomalies, giving rise to both LCHs and NICHs. 8,9 It remains unclear how identical somatic mutations can give rise to distinct clinical phenotypes.…”

Section: 34mentioning

confidence: 99%

513 GNA14 somatic mutation causes congenital and sporadic vascular tumors by MAPK activation

Lim

Bacchiocchi

Qiu

et al. 2017

Journal of Investigative Dermatology

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Vascular tumors are among the most common neoplasms in infants and children; 5%-10% of newborns present with or develop lesions within the first 3 months of life. Most are benign infantile hemangiomas that typically regress by 5 years of age; other vascular tumors include congenital tufted angiomas (TAs), kaposiform hemangioendotheliomas (KHEs), and childhood lobular capillary hemangiomas (LCHs). Some of these lesions can become locally invasive and unresponsive to pharmacologic intervention, leading to significant complications. Recent investigation has revealed that activating mutations in HRAS, KRAS, NRAS, GNAQ, and GNA11 can cause certain types of rare childhood vascular tumors, and we have now identified causal recurrent somatic activating mutations in GNA14 by whole-exome and targeted sequencing. We found somatic activating GNA14 c.614A>T (p.Gln205Leu) mutations in one KHE, one TA, and one LCH and a GNA11 c.547C>T (p.Arg183Cys) mutation in two LCH lesions. We examined mutation pathobiology via expression of mutant GNA14 or GNA11 in primary human endothelial cells and melanocytes. GNA14 and GNA11 mutations induced changes in cellular morphology and rendered cells growth-factor independent by upregulating the MAPK pathway. Our findings identify GNA14 mutations as a cause of childhood vascular tumors, offer insight into mechanisms of oncogenic transformation by mutations affecting Gaq family members, and identify potential targets for therapeutic intervention.

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Symptomatic Congenital Hemangioma and Congenital Hemangiomatosis Associated With a Somatic Activating Mutation in GNA11

Cited by 36 publications

References 10 publications

Multifocal congenital hemangioma: Expanding the pathogenesis of “neonatal hemangiomatosis”

Multifocal congenital hemangioma: Expanding the pathogenesis of “neonatal hemangiomatosis”

Atypical presentations of congenital hemangiomas: Extending the clinical phenotype

513 GNA14 somatic mutation causes congenital and sporadic vascular tumors by MAPK activation

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