Registration is now open for the 2014 NOVA Family Conference
May 30 – June 1 2014 Charleston, SC
Infantile Hemangioma is the most common benign tumor o infancy and children. Although benign, patients diagnosed with IH often experience complications. It is often challenging for parents to determine if and when treatment is necessary. Many primary care physicians delay referral to physicians with experience in the diagnosis and treatment of IH based on the misconception that these lesions do not require treatment.
We have known for nearly 30 years that most infantile Hemangioma (IH) do not require medical intervention since they spontaneously regress in a process known as involution. Most of these lesions resolve to an acceptable state. However; a significant subset of Hemangioma patients do require treatment. Dr. Drolet and associates report that many patients experience complications including ulceration, bleeding, pain, visual impairment, airway impairment, residual scaring and permanent disfigurement. Dr. Frieden and associates have divided these complications into 3 categories as reasons to intervene.
- · Ulceration
- · Disfigurement
- · Impairment of function or vital structures
It is also noted that certain IH have a risk of structural anomalies which must be addressed.
Current research suggest s that the decision of if and when to intervene requires an understanding and “detailed knowledge” of the natural history of Hemangioma and the clinical indications of the increased risk. The data from recent studies reveal insights into the identification, evaluation and management of IH. The indication for treatment and the type of treatment; specifically medical treatments like corticosteroids, Beta-Blockers and Vincristine is revealed by Dr. Drolet’s recent publication.
NOVA Thanks all of the researchers and physicians dedicated to continuing the work to understanding the diagnosis and treatment of IH and other vascular anomalies. This work simplifies the decisions parents must make in seeking treatment for their child.
National Organization of Vascular Anomalies
1. Br J Dermatol. 2013 May 22. doi: 10.1111/bjd.12436. [Epub ahead of print], Hemangioma: Clinical Course, Complications, and Management. Luu M., Frieden IJ.
2. Am J Clin Dermatol. 2013 Apr;14(2):111-23. doi: 10.1007/s40257-013-0008-x., Infantile hemangiomas : an update.
NOVA has two Facebook pages: https://www.facebook.com/#!/pages/National-Organization-of-Vascular-Anomalies-NOVA/98394768856 and https://www.facebook.com/#!/groups/NOVANews/ join us!
Our laboratory and collaborators at the Medical College of Wisconsin/Children’s Hospital of Wisconsin are getting closer every day in our mission to identify the cause of PHACE syndrome. We are using whole genome sequencing to look for changes in genes that could cause PHACE syndrome. To successfully complete this work, we need to obtain more grant funding. Our grant will be much stronger if we have DNA from 100 families- that means getting a blood sample or buccal swab from both parents. We already have some initial results, but we can only make sense of these if we can compare the results to the parents’ DNA samples. In addition, the most helpful information is coming from tissue samples. If your child has any surgery for the revision of the hemangioma or aorta, please let us know!
Dawn Siegel, MD
Beth Drolet, MD
The PHACE syndrome Clinical Registry and Genetic Repository
Medical College of Wisconsin/Children’s Hospital of Wisconsin
After 25 years of searching, the Sturge-Weber Foundation (SWF) is thrilled to join patients, physicians, researchers and government agencies in celebrating the identification of the gene mutation responsible for Sturge-Weber syndrome and port-wine birthmarks. The new research was published online today in The New England Journal of Medicine. http://www.sturge-weber.org/
FOR IMMEDIATE RELEASE
Thursday, May 31, 2012
Researchers at Boston Children’s Hospital identify a genetic cause for CLOVES, a rare but debilitating overgrowth and malformation syndrome
Discovery opens doors to targeted therapeutic development and to understanding other, similar disorders
Boston, Mass.—Using advanced technologies for rapidly sequencing and analyzing DNA from clinical and pathologic samples, a multidisciplinary research team consisting of geneticists, pathologists and surgeons at Boston Children’s Hospital has identified the genetic basis for CLOVES syndrome, a rare congenital malformation and overgrowth disorder.
The discovery raises the hope that, for the first time, it will be possible to develop targeted medical treatments capable of delaying, reversing or possibly preventing CLOVES’s debilitating consequences. Importantly, it also demonstrates the potential of advanced DNA sequencing technologies for identifying the underlying molecular roots of malformation disorders that are genetic but not hereditary.
The team—led by Matthew Warman, MD, director of the Orthopedic Research Laboratories at Boston Children’s, and Kyle Kurek, MD, of the hospital’s department of Pathology, and members of the hospital’s Vascular Anomalies Center—reported the discovery today in the online edition of the American Journal of Human Genetics.
Some 90 children worldwide have been diagnosed with CLOVES (which stands for Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevis, Spinal/skeletal anomalies/scoliosis) since 2006, when the condition was first characterized by Boston Children’s Ahmad Alomari, MD, and investigators at the National Institutes of Health. Alomari co-directs the Vascular Anomalies Center with Steven Fishman, MD, and John Mulliken, MD; all three are authors on the paper.
The clinical features of CLOVES—in general a combination of fatty growths in the torso, vascular and skin anomalies, overgrowth in or deformities of limbs or extremities and spinal problems such as scoliosis—can vary greatly from child to child. Presently there is no cure for CLOVES, only surgical treatments aimed at alleviating symptoms or managing the syndrome’s progression.
Until now, the exact nature of the genetic defect or defects that cause CLOVES has remained a mystery.
“CLOVES is dynamic, presenting itself in new ways all the time, even within the same patient,” said Fishman, who with Alomari and others in the Vascular Anomalies Center has treated numerous children with CLOVES. “With this discovery we are optimistic that it will now be possible to develop treatments that take less of a shotgun approach and which could prevent the syndrome’s progression.”
The researchers started from the assumption that CLOVES is genetic but not inherited, because the syndrome always appears sporadically and is never passed from affected parents to their children; nor do the parents of affected children show signs of the syndrome.
“We suspected that a mutation in a single gene would be the cause, but in the beginning we weren’t sure if the mutation would affect the gene’s coding sequence or genetic regions that determine how a gene’s expression is regulated.” said Warman. “We also did not know whether the mutation would be the same across patients.”
To identify the disease-causing mutation, Warman, Kurek and their colleagues used massively parallel (also known as next generation) sequencing technologies to read and compare the full exomes (all protein-coding gene sequences) of affected and unaffected tissues from several CLOVES syndrome patients treated in the Vascular Anomalies Center at Boston Children’s.
The team found that between six and 60 percent of cells in each individual’s affected tissues contained mutations in a gene called PIK3CA, a component of a key molecular pathway regulating cell division and growth. Even though the precise mutations differed slightly between the patients, each mutation—a simple replacement of one DNA base for another, altering the structure of the protein PIK3CA encodes—has the effect of activating the pathway in the absence of external signals promoting growth.
The mutations were absent in the unaffected tissues tested.
Based on their findings, Warman and his colleagues determined that CLOVES is the result of a somatic mosaic mutation—a mutation that appears only in a portion of an individual’s cells, rather than being present throughout his or her entire body.
“These are point mutations that likely arise spontaneously in a single cell during embryonic or fetal development, and which are passed on only to cells derived from that original mutant cell,” Warman explained. “The presence of a large percentage of unmutated cells within affected tissues suggests that there is a kind of innocent bystander effect occurring, where unmutated cells respond to abnormal signals produced by cells carrying the mutation and contribute to the syndrome’s malformations and overgrowths.”
Both Fishman and Warman credit the interdisciplinary environment at Boston Children’s with making the team’s breakthrough possible.
“Gene discovery in rare conditions like CLOVES requires a combination of circumstances nearly unique to Children’s: doctors who classified CLOVES as a new condition; tissues from the large number of CLOVES patients referred to the Vascular Anomalies Center because of our experience with unusual vascular and overgrowth conditions; and world-class molecular genetic expertise,” Fishman said. “The methods Drs. Warman and Kurek developed to find these mutations are very exciting and could help many other children with sporadically occurring diseases that are not hereditary but likely genetic.”
“This project represents the perfect marriage of surgery, pathology and genetics,” said Warman. “It was only through the combined efforts of multiple specialists—the surgeons in the Vascular Anomalies Center who had the foresight to save for future genetic studies the tissues resected from their patients, the pathologists who could tease apart affected and unaffected tissues from within the lesions, and the geneticists with the tools to sequence and compare unaffected and affected genomes—that this breakthrough was possible.
“Having now found these driving mutations in CLOVES,” he continued, “we have a good starting point from which to both develop models to understand how mutations in PIK3CA cause malformation and overgrowth and to determine which drugs and other therapies can be used safely and successfully to improve the lives of individuals with CLOVES and other conditions with similar clinical characteristics, such as Klippel-Trenaunay syndrome.”
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Manton Center for Orphan Disease Research and the Stuart and Jane Weitzman Family Vascular Anomalies Fund (both at Boston Children’s Hospital), and the Howard Hughes Medical Institute.
Boston Children’s Hospital is home to the world’s largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including nine members of the National Academy of Sciences, 11 members of the Institute of Medicine and nine members of the Howard Hughes Medical Institute comprise Boston Children’s research community. Founded as a 20-bed hospital for children, Boston Children’s today is a 395 bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Boston Children’s also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about research and clinical innovation at Boston Children’s, visit: http://vectorblog.org.
The National Organization of Vascular Anomalies is proud to announce the award of a Grant to the Children’s Hospital of Milwaukee for PHACE. The first part of the Grant will be used to print/publish and distribute 150 Patient Handbooks of PHACE. The second part of the Grant will be used to design, launch and host a web site for the PHACE registry, research and digital copy of the PHACE Patient Handbook.
Thank you to all who have donated to NOVA making our Grant Program possible.
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NOVA is pleased to announce our 2012 Family Conference
October 5-7, 2012 Cincinnati Children’s Hospital, Cincinnati, OH & Kingsgate Marriott Hotel, Cincinnati, OH
The National Organization of Vascular Anomalies offers a unique medical conference for individuals affected by hemangioma, vascular malformation and related syndromes. We bring together nationally renowned physicians to present a medical seminar on the current approaches in the care and management of vascular anomalies. NOVA Family Conferences are free to families affected by Vascular Anomalies.
Presentations on the diagnosis and treatment of vascular anomalies, the latest scientific information and details on the spectrum of disorders will be featured at the 2012 Conference. Research, Registry and Clinical Trial information will be presented.
The 2012 NOVA Family Conference also offers families an opportunity to meet other families, share their concerns, hopes and prayers.
Registration can be completed on line at
Updates will be posted on facebook.
Please Return Registration to:
PO Box 38216
Greensboro, NC 27438-8216
Conference Update: Hotel Reservations for the NOVA Family Conference may be made by going to www.kingsgatemarriott.com and entering the Group Code NFCNFA. You can also call 1-888-720-1299 and ask for the NOVA Family Conference room block NFC. Standard room rates are $102/night. The block begins on 10/4/2012 and runs through 10/6/2012. NOVA will not be making reservations for guests. We will have general conference registration information available soon.
We have had a lot of discussion on face-book concerning the genetic/inheritance of hemangioma. It is the generally understood that infantile hemangioma is sporadic, that there is not an inheritance pattern. However there has been some families where it has appeared that there was more of an incidence then the rest of the population. This has cause concern for many parents, wondering if a sibling might also have a significant hemangioma.
First lets go over some basic terminology:
Congenital- simply means you were born with it. This does not necessarily mean that it is inherited for that it was passed down from your parents.
Genetic:- when this term is used it may mean that there is an inheritance pattern but it may also simply mean that a mutation or change in the gene occurred randomly.
Inherited- this is the term that when used is meant that there is a known inherited link in a family. There are many diseases that run in families, that there is a genetic cause that is passed down.
This is an over simplification of things but it will help you keep things straight.
In vascular anomalies we have two main groups. Tumors and Malformations.
The most common benign vascular tumor is the Infantile Hemangioma. It is this lesion that primarily occurs randomly. There is also the Congenital Hemangioma either the RICH or NICH forms. These are less common and while the child is born with a fully formed hemangioma it is not known to be inherited.
There are many types of vascular malformations. Malformations may occur in the veins, arteries, smaller vessels and even the lymphatic vessels.
Scientists have identified Genes and markers associated with malformations and hemangiomas. They have been able to test for the presence of the genes and markers to help distinguish between the types of anomalies.
MOST vascular anomalies are considered non-hereditary. Through the detailed analysis they have discovered inheritance forms of some vascular anomalies. They have identified mutations in genes that have cause familial malformations in RARE cases.
*Tie-2 gene (angiopoietin receptor): in mucocutaneous venous malformations (VMCM0
*Glomulin: in glomuvenous malformations (GVM)
*RASA1: in campllary malformations-arteriovenous malformations (CM-AVM)
The identification of these genes has allowed for more accurate and precise diagnosis, differential diagnosis, evaluation of variability in patients with known mutations and the study of treatments in identified patients. Identification of these genes will allow the clinician to determine the type of vascular anomaly and differentiate between malformation and tumor.
In infantile hemangioma there was an identified gene in one family that appeared in the published work of Doug Marchuk at Duke University. There have also been identified biomarks that have helped researchers understand the pathogenesis of hemangioma and to distinguish between infantile hemangioma/congenital hemangioma and malformations. At this time hemangioma is still primarily considered to be occurring sporadically.
Vikkula, M; Pathogenesis and Genetics of Vascular Anomalies, Ann Chir Plast Esthet, 2006 Aug-oct 51(4-5) .
Nauyen, VA; Kutzner, H; Furhapter, C; tzankov, A; Sepp, N, Infantile hemangioma is porliferation of LYVE-1-Negative blood endothelial cells without lymphatic competence, Modern Pathology, 2006 Feb:192(2):291-8
Mulliken, John, Enjolras, Odile, Congenital Hemangioma and Infantile Hemangioma: missing links. Journal of American Academy of Dermatology, July 2004; (875-881)