Note: research summaries are intended for patient/parent educational purposes. If you are interested in reading more about a topic/article, the link that follows will take you to the full abstract and reference. Unless an article is available as an open-access resource, you will need to contact your local library, hospital, or medical provider to obtain a copy of the full article due to copyright restrictions.

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Delphi Consensus on Diagnostic Criteria for LUMBAR Syndrome

​September 2024

The Journal of Pediatrics, Volume 272, September 2024

Objective: To develop consensus on diagnostic criteria for LUMBAR syndrome, the association of segmental infantile hemangiomas that affect the Lower body with Urogenital anomalies, Ulceration, spinal cord Malformations, Bony defects, Anorectal malformations, Arterial anomalies and/or Renal anomalies.

Click here for study

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Multi-center Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10

Journal of Pediatrics Published: January 11, 2024DOI: https://doi.org/10.1016/j.jpeds.2024.113907

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Objective:  To characterize long-term outcomes of PHACE syndrome. Study design: Multi-center study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ³10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains.

 

Facing PHACE Twenty-five Years Later

Journal of Vascular Anomalies 2(4):p e027, December 2021

Authors: Braun, Mitchell T.a; Mathes, Erin F.b; Siegel, Dawn H.c; Hess, Christopher P.d; Fox, Christine K.e; Frieden, Ilona J.b

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Objective of the study: To review the key features of PHACE syndrome over the past 25 years, highlighting evaluation, management, current gaps in knowledge, and potential next steps in research and patient-centered care.

Click here for a link to the study

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Evaluating the Safety of Oral Propranolol Therapy in Patients With PHACE Syndrome

JAMA Dermatol. 2020 Feb; 156(2): 186–190.

Published online 2019 Dec 11. doi: 10.1001/jamadermatol.2019.3839

Authors: Olsen, G., Hansen, L., Stefanko, N., Mathes, E., Puttgen, K., Tollefson, M., Lauren, C., Mancini, A., McCuaig, C., Frieden, I., Adams, D.,  Baselga, E., Chamlin, S., Gupta, D., Frommelt, P., Garzon, M., Horii, K., Klajn, J., Maheshwari, M., Newell, B., Nguyen, H., Nopper, A., Powell, J.,  Siegel, D., Drolet, B.

Outlet: JAMA Dermatology

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This multi-center cohort study describes the use of oral propranolol in 76 infants with PHACE syndrome with no reports of serious adverse events. There was no significant difference in the rate of serious adverse events between patients with PHACE syndrome and patients without PHACE syndrome who received oral propranolol for infantile hemangioma.

Click here for a link to the study.

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PHACE Syndrome — Before and After Propranolol Therapy
February 2018
Authors: Disse, S. C., Zemlin, M., Mueller, C., & Meyer, S. 
Outlet: The Journal of pediatrics, 193, 275.

 

This case report describes a little girl with PHACE syndrome, before and after treatment with propranolol.  Like so many other children with PHACE, she was first misdiagnosed with another condition (i.e., port wine stain) but then later found to have PHACE syndrome.  Her hemangioma grew very rapidly at first, so propranolol treatment was started.  In this case she was treated for 3 years with propranolol with excellent results and no complications. The pictures in this report show the progression and outcomes of her treatment.

Click here for a link to the study. 

 

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Moyamoya vasculopathy in PHACE syndrome: six new cases and review of the literature

December 2017

Authors: Tortora, D., Severino, M., Accogli, A., Martinetti, C., Vercellino, N., Capra, V., Rossi, A. & Pavanello, M.  

Outlet: World Neurosurgery, 108, 291-302.

 

The most common problem in PHACE syndrome, aside from large facial hemangiomas, are differences in the arteries of the brain.  As children with PHACE grow up, these artery problems can worsen and may lead to headaches, seizures, and even stroke.  Therefore, it is important to study the arteries carefully and find which children are at highest risk for serious problems.  Those whose arteries are the most severely affected need to be studied with imaging more often, to decide on management including possible surgery to correct these problems. The abnormal blood vessels in the brain in PHACE can lead to something called “Moyamoya vasculopathy”. The word “Moyamoya” in Japanese means “puff of smoke”.  It refers to the appearance of many small arteries coming off of larger arteries and can be detected with MRI scans. Though these tiny blood vessels are believed to be the body’s attempt to increase blood flow to the affected areas, they can increase the risk for a stroke. This study presents detailed information about six new cases of children with PHACE and moyamoya disease, and reviews another 15 cases that had been published before.  The authors report that there are surgical treatments that can be done for these complicated problems with good results. 

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Prenatal Risk Factors for PHACE Syndrome: A Study Using the PHACE Syndrome International Clinical Registry and Genetic Repository

November 2017

Authors: Wan, J., Steiner, J., Baselga, E., Blei, F., Cordisco, M., Garzon, M. C., & Metry, D. Outlet: The Journal of Pediatrics, 190, 275-279.

 

The cause of PHACE syndrome is unknown. Many past studies have reported in detail about possible pregnancy-related factors that could be related to PHACE syndrome. In this study, mothers of children with PHACE completed detailed questionnaires about their pregnancies. The results revealed that rates of certain kinds of placental problems were greater among kids with hemangiomas and PHACE than in the general population. Overall there was no single prenatal risk factor that was found to be a cause of PHACE, and no clear genetic cause has yet been identified. There are no clear differences the features of PHACE found in boys vs girls with PHACE, even though PHACE is more common in girls.  Most of the kids are white (Caucasian), but we know that PHACE can occur in all races. Future research will continue to examine how genetics and prenatal factors might work together to cause PHACE.

Click here for the study.

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Structural malformations of the brain, eye, and pituitary gland in PHACE Syndrome

November 2017

Authors: Steiner, J. E., McCoy, G. N., Hess, C. P., Dobyns, W. B., Metry, D. W., Drolet, B. A., Maheshwari, M, & Siegel, D. H.  

Outlet: American Journal of Medical Genetics Part A, 176(1), 48-55.

 

PHACE is a syndrome including facial hemangiomas and an assortment of birth defects affecting the arteries, heart, brain, and eyes. About half of all PHACE kids have some problems of the brain itself, which in some cases can interfere with development of skills like walking, talking, reading, etc. This study was a look back at children already diagnosed with PHACE to better understand abnormal Magnetic Resonance Imaging (MRI) findings. The study looked at 55 patients with PHACE who had good quality MRI scans among 224 PHACE patients enrolled in the PHACE syndrome International Clinical Registry.  The authors evaluated these brain MRI scans carefully.  Of the 55 scans reviewed, nearly two-thirds did show at least one brain abnormality. The most common was under-development of a part of the back of the brain in an area called the cerebellum, which helps control balance and motor development.  The study also found some problems with the pituitary gland – also known as the “master gland”- which helps control production of cortisone, growth hormone, and other hormones.   Other problems found included abnormalities of the eyes or the nerves to the eyes.  This study confirms a lot of what was already known about the brain abnormalities in PHACE but it gives us a clearer picture of the specific problems and also the importance of eye and pituitary structure problems in some individuals with PHACE. 

Click here for the study.

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PHACE Syndrome International Registry Headache Survey

Authors: JiaDe Yu, MD,1 Dawn H. Siegel, MD,1 Beth A. Drolet, MD,1 Francine Blei, MD,2 Leon G. Epstein, MD,3 Denise Metry, MD,4 and Geoffrey L. Heyer, MD5

Outlet: J Child Neurol. 2016 Mar; 31(4): 468–473

PHACE syndrome is a neurocutaneous disorder often involving the cerebral vasculature. PHACE patients appear to have early-onset and severe headaches more commonly than children without PHACE. The objective of this study was to characterize the clinical features and prevalence of headache by conducting a cross-sectional survey of families in two large PHACE registries. Sixty-six percent of eligible families completed the survey in which 62.7% of respondents reported headaches. Average age of headache onset was 48.8 months. Females were more likely to have headaches (68.6% versus 30.8%, p=.014). Families reported associated migrainous features including nausea (62.5%), vomiting (37.5%), photophobia (75%), and phonophobia (75%). Headaches occurred at least weekly in 29.4%, lasted ≥1 hour in 85.4%, and led to ≥1 hospital admission in 15.7%. Three respondents with headaches had at least one ischemic stroke. We demonstrated that headaches are common among PHACE patients, develop at an early age, and have migrainous features.

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Neurodevelopmental Outcomes in Children with PHACE Syndrome

June 2016

Authors: Brosig, C. L., Siegel, D. H., Haggstrom, A. N., Frieden, I. J., & Drolet, B. A.

Outlet: Pediatric Dermatology, 33(4), 415-423.

 

Children with PHACE syndrome have facial hemangiomas, and may have problems with their heart, blood vessels, and eyes.  90% of children with PHACE also have some type of brain abnormality detected on MRI.  These could cause slower development of skills like speaking, paying attention, reading, and walking. Also, children with PHACE may have behavior and emotional problems.  This study was performed to find out how many children with PHACE have developmental delays and behavior difficulties. 25 children with PHACE syndrome completed a day of testing. Tests of intelligence, memory, language, strength, and coordination were completed.  Parents were asked their about children’s emotions and behavior. The results of these tests and interviews were compared to the performance of children without PHACE. Most children with PHACE were no different from other children without PHACE. However, some children with PHACE had developmental delays or learning problems.  All specialists who care for children with PHACE need to be aware of the possibility of learning problems and psychological issues that can be part of this condition.

Click here for the study.

 

Infantile Hemangiomas and Structural Anomalies: PHACE and LUMBAR Syndrome

September 2016

Authors: Luu, M., & Frieden, I. J.  

Outlet: Seminars in Cutaneous Medicine and Surgery (Vol. 35, No. 3, pp. 117-123).

 

Doctors Liu and Frieden describe in detail two well studied syndromes where infantile hematomas have internal conditions as well.  The first syndrome PHACE has hemangiomas involving the face and scalp together with abnormalities involving brain, heart and other blood vessel problems.   In the other condition, LUMBAR syndrome, hemangiomas of the lower half of the body, especially the diaper area can have problems with the spinal cord, kidneys and genital structures. This article tells how to recognize simple benign hemangiomas that may require only good care for the skin problem itself, from the larger “segmental” hemangiomas that require further evaluations to look for other problems.  It explains what studies are needed for these syndromes, and some of the likely specialists that will be needed to manage problems that might be present.  It also reviews the main treatments for these hemangiomas.

Click here for the study.

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Aortic arch repair in children with PHACE Syndrome

September 2016

Authors: Caragher, S. P., Scott, J. P., Siegel, D. H., Mitchell, M. E., Frommelt, P. C., & Drolet, B. A.  

Outlet: The Journal of Thoracic and Cardiovascular Surgery., 152(3), 709-717.

 

This study looks back at seven children with PHACE Syndrome who required surgery to repair aortic arch anomalies.  The aorta is the body’s largest artery and other major arteries including those to the neck, brain, and arms branch off of the aorta.   In PHACE syndrome, these arteries, as well as the aorta, can be affected. When the aorta and the large vessels branching from it are narrowed or oddly shaped, it can lead to poor circulation or weakness of the blood vessels, which can be very serious, even life-threatening.  The 7 children reported underwent different complicated surgeries, which are described in detail in this paper.  Some children needed repeat operations as they grew older.  This paper adds to the knowledge of what kind of aorta and heart problems are found in PHACE and some of the successful treatments surgeons can use to repair them.

Click here for the study.

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New Care Guidelines for Patients with PHACE

November 2016

 

PHACE Syndrome Community's Medical Advisory Board heard members of our community loud and clear. Parents can feel overwhelmed by a child's diagnosis of PHACE Syndrome, particularly because so many doctors have never heard of it before. This 12-page paper, published by the prestigious  The Journal of Pediatrics, compiles all the latest research on best protocols for treatments of individuals with PHACE Syndrome. Click here or the title above to download the report.

Click here for Guidelines

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Results of the first pediatric study evaluating efficacy of propranolol

Feb. 20, 2015

 

Pierre Fabre announced today that the results from the landmark clinical trial evaluating the first ever pediatric propranolol treatment for use in certain types of infantile hemangiomas resulted in significantly higher complete or nearly complete resolution of the target hemangioma. This data has just been published in the New England Journal of Medicine and specifically shows that the dose regimen of 3mg of propranolol base (3.4mg propranolol hydrochloride) per kilogram per day for 6 months has a significantly higher successful treatment rate than placebo (60.4% vs 3.6%; p<0.0001).

Click here for the complete press release.

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Therapy of ulcerated hemangiomas

July-August 2013

Outlet: Journal of Cutaneous Medicine and Surgery

 

BACKGROUND: Cutaneous ulceration is the most common complication of infantile hemangiomas (IHs) seen in a pediatric dermatology practice. OBJECTIVE: The most effective treatments in our experience are compared to those in the current literature. METHODS: The study was a retrospective chart review of therapy of 169 ulcerated IHs at a tertiary care pediatric hospital and a literature review. RESULTS: Combination therapy was the rule. Local wound care was required in all, pain management in 72%, pulsed dye laser in 42%, infection control in 38%, diminution of the hemangioma through systemic therapy in 36%, and suppression of bleeding in 2%.LIMITATIONS: A retrospective review compared to a case-control study has inherent bias. In addition, our cases were all at a tertiary referral center.

 

CONCLUSION: All ulcerated IHs benefit from local barrier creams or dressings. Pulsed dye laser, antibiotics, topical morphine 0.1% in hydrogel, topical becaplermin, and, most importantly, systemic therapy (especially propranolol) to reduce the hemangioma may be useful.

Click here for the study.

 

Stroke in children with posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities (PHACE) syndrome: a systematic review of the literature

March 2012

 

Background and purpose: PHACE is an acronym for posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities. Several case reports of arterial ischemic stroke (AIS) in individuals with PHACE have been published, but risk factors for AIS in PHACE have not been clearly defined. The objective of this article is to review all cases of stroke in PHACE in children and describe clinical characteristics that may be associated with an increased risk of AIS.

Click here for the study

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Medical Publications

The NCBI has been charged with creating automated systems for storing and analyzing knowledge about molecular biology, biochemistry, and genetics; facilitating the use of such databases and software by the research and medical community; coordinating efforts to gather biotechnology information both nationally and internationally; and performing research into advanced methods of computer-based information processing for analyzing the structure and function of biologically important molecules. Follow the links below to search the National Center for Biotechnology Information (NCBI) database.

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PHACE Syndrome

https://www.ncbi.nlm.nih.gov/pubmed/?term=phace+syndrome

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Lumbar Syndrome

https://www.ncbi.nlm.nih.gov/pubmed/?term=lumbar%20syndrome

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