Longitudinal Study of Neurologic, Cognitive, and Radiologic Outcomes of PHACE Syndrome

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

Inclusion criteria

• Fulfills definite or possible PHACE syndrome diagnostic criteria, per consensus statement November 2008;
• Child is between 4-6 years of age; and
• Parents able and willing to travel to our center (Medical College of Wisconsin) for evaluations.

Exclusion criteria

• Patients with known genetic disorders in addition to PHACE syndrome;
• Patients unable to undergo adequate MR imaging due to pacemaker or other MRI-incompatible implant(s); or
• Non-English and non-Spanish speaking patients will be excluded due to interpreter-related inconsistencies in neurocognitive testing. Clinical Evaluation: A standardized electronic data collection form will be designed. Demographic data, clinical -