PHACE Syndrome Clinical Trial
Official title:
Longitudinal Study of Neurologic, Cognitive, and Radiologic Outcomes in PHACE Syndrome
The overall goal of this 2-year pilot project is to utilize interdisciplinary strategies to determine the prevalence and type of neurodevelopmental impairment in PHACE syndrome, a rare vascular syndrome, and to rapidly translate discovery into clinical care guidelines that will identify at risk infants so early intervention can be initiated. Infantile hemangioma is the most common benign tumor of infancy, with an incidence estimated between 4-5%. A subgroup of patients with infantile hemangiomas exhibits additional associated structural anomalies of the brain, cerebral vasculature, eyes, aorta, heart, and chest wall in the rare neurocutaneous disorder called PHACE syndrome (OMIM 606519). PHACE refers to Posterior fossa anomalies, Hemangioma, Arterial lesions, Cardiac abnormalities/aortic coarctation, and abnormalities of the Eye. Affected children have multi-organ involvement, and an increasing number of cerebral, cerebellar, and cerebrovascular anomalies are being described; however, the significance of these neuroradiologic findings is not known. As the investigators' neonates with hemangiomas have grown into young children, neurodevelopmental impairment has become more evident, even among patients without MRI evidence of stroke or structural brain anomalies. Some infants develop progressive cerebral arterial disease leading to a moyamoya-like vasculopathy and ischemic stroke. An interdisciplinary research project studying brain and cerebral vascular imaging in concert with neurological, psychological, behavioral, neurodevelopmental, and quality of life outcome measures has never been conducted. Diagnostic and management guidelines are also lacking. The investigators' long-term goal is to develop medical and/or surgical therapeutic interventions that improve the overall health of children with PHACE syndrome. This novel project constitutes the first study of the most devastating feature of PHACE syndrome: the neurodevelopmental sequelae.
Aim 1) Establish a cohort of 30 well-characterized patients with PHACE syndrome and enhance
existing tissue and DNA banks to facilitate future investigation.
We will use rigorous phenotyping strategies to establish a cohort of 30 patients with PHACE
syndrome 4-6 years of age, and collect neuroimaging studies and patient tissue and DNA
samples to enhance an existing tissue repository to facilitate future studies, such as
validation of biomarkers.
Aim 2) Determine the prevalence and describe the spectrum of neurodevelopmental impairment
in a cohort of patients 4-6 years of age with PHACE syndrome.
Given the multiple risk factors for neurodevelopmental deficits in PHACE patients, we
propose a comprehensive assessment of a cohort of patients 4-6 years of age, this age range
represents a critical period, as it is the time that most children enter the formal
educational system and it allows for a more thorough evaluation of neurodevelopmental
skills. Upon completion of this 2-year study we expect to have immediate impact on clinical
care by identifying specific deficits in this cohort. Once identified and quantified, we
will publish the data with clinical guidelines for patient management including age and
frequency of neuroimaging, frequency of neurologic evaluation, and age and utility of
neurodevelopmental assessment. We anticipate that these guidelines will identify at risk
infants and early intervention can be initiated, resulting in improved functional outcomes.
In addition, this data will provide a cost-effective functional outcome methodology that can
be used for clinical trials and to validate biomarkers identified in this pilot study.
Aim 3) Identify potential clinical, molecular, biochemical, and imaging biomarkers aimed at
early detection and risk stratification of cerebrovasculopathy and neurodevelopmental
impairment.
We hypothesize that certain risk factors including, but not limited to, genotype, hemangioma
size, hemangioma location, cerebral anomalies, cerebellar anomalies, and cerebrovascular
anomalies predispose patients to progressive vasculopathy. We will determine risk factors
and identify biomarkers for progressive cerebrovascular disease. Based on this information
we will establish guidelines for serial and diagnostic cerebrovascular imaging and develop a
method of risk-stratification that will allow for early clinical prediction and intervention
of long-term neurodevelopmental prognosis. Specific Aims
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Enrolling by invitation |
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| Completed |
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| Recruiting |
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