Longitudinal Study of Neurologic, Cognitive, and Radiologic Outcomes of PHACE Syndrome
Condition: PHACE Syndrome
MeSH terms: Syndrome
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Children between the ages of 4-6 years who fulfill the diagnostic criteria for PHACE
        syndrome will be contacted for enrollment.