PHACE Syndrome
Introduction to PHACE Syndrome
PHACE syndrome is a rare neurocutaneous disorder characterized by a constellation of congenital anomalies. The acronym PHACE stands for the major features of the syndrome:
- Posterior fossa brain malformations
- Hemangiomas of the face, neck, and/or scalp
- Arterial anomalies
- Cardiac defects and coarctation of the aorta
- Eye abnormalities
PHACE syndrome primarily affects females, with a female-to-male ratio of approximately 9:1. The exact prevalence is unknown, but it is estimated to occur in 1 in 25,000 newborns. It is considered the most common neurocutaneous disorder associated with infantile hemangiomas.
Clinical Features of PHACE Syndrome
The clinical presentation of PHACE syndrome can vary significantly among affected individuals. The key features include:
1. Cutaneous Hemangiomas
- Large, segmental hemangiomas of the face, neck, and/or scalp
- Often present at birth or develop within the first few weeks of life
- Typically follow a dermatomal distribution
2. Posterior Fossa Anomalies
- Dandy-Walker malformation
- Cerebellar hypoplasia or dysplasia
- Arachnoid cysts
3. Arterial Anomalies
- Persistent embryonic arteries
- Aberrant origin or course of major arteries
- Stenosis or occlusion of cerebral arteries
- Increased risk of stroke
4. Cardiac Defects
- Coarctation of the aorta (most common)
- Ventricular septal defects
- Atrial septal defects
- Patent ductus arteriosus
5. Eye Abnormalities
- Persistent fetal vasculature
- Optic nerve hypoplasia
- Retinal vascular anomalies
- Microphthalmos
6. Additional Features
- Midline ventral defects (sternal clefting, supraumbilical raphe)
- Endocrine abnormalities (thyroid dysfunction, growth hormone deficiency)
- Hearing impairment
- Developmental delays
Diagnosis of PHACE Syndrome
Diagnosis of PHACE syndrome is based on clinical criteria and imaging studies. The 2016 revised diagnostic criteria include:
Definite PHACE Syndrome
- Facial hemangioma >5 cm in diameter plus one major criterion or two minor criteria
Possible PHACE Syndrome
- Facial hemangioma >5 cm in diameter plus one minor criterion
- Hemangioma of the neck or upper torso plus one major criterion or two minor criteria
Diagnostic Workup
- Imaging studies:
- MRI and MRA of the brain, neck, and chest
- Echocardiogram
- Ophthalmologic examination
- Genetic testing:
- Currently, no specific genetic test is available for PHACE syndrome
- Genetic consultation may be recommended to rule out other syndromes
- Additional evaluations:
- Audiologic assessment
- Endocrine evaluation
- Developmental assessment
Management of PHACE Syndrome
Management of PHACE syndrome requires a multidisciplinary approach and is tailored to the specific needs of each patient. Key components include:
1. Treatment of Hemangiomas
- Oral beta-blockers (e.g., propranolol) as first-line therapy
- Topical beta-blockers for smaller lesions
- Systemic corticosteroids in selected cases
- Laser therapy or surgery for residual lesions
2. Neurological Management
- Regular neurological examinations
- Anticoagulation therapy for patients with high-risk arterial anomalies
- Neurosurgical intervention for structural brain anomalies if needed
3. Cardiac Care
- Surgical repair of cardiac defects (e.g., coarctation of the aorta)
- Ongoing cardiac monitoring
4. Ophthalmologic Care
- Regular eye examinations
- Management of specific ocular complications
5. Endocrine Management
- Thyroid function monitoring
- Growth hormone replacement if deficient
6. Developmental Support
- Early intervention services
- Speech and language therapy
- Occupational and physical therapy as needed
7. Long-term Surveillance
- Regular follow-up with a multidisciplinary team
- Periodic imaging studies to monitor vascular anomalies
Prognosis and Long-term Outcomes
The prognosis for children with PHACE syndrome varies depending on the severity and extent of involved organ systems:
- Overall, many children with PHACE syndrome have a good long-term prognosis with appropriate management
- Neurodevelopmental outcomes are generally favorable, with most children achieving normal cognitive development
- Stroke remains a significant risk, particularly in early childhood
- Facial hemangiomas typically involute over time, but may leave residual skin changes
- Ongoing monitoring for potential late-onset complications is essential
- Quality of life can be impacted by facial appearance, surgical interventions, and associated medical conditions
Research and Future Directions
Ongoing research in PHACE syndrome focuses on several key areas:
- Genetic basis: Identifying genetic mutations or pathways involved in PHACE syndrome
- Pathogenesis: Understanding the developmental mechanisms leading to the diverse features of PHACE
- Improved diagnostics: Developing more sensitive and specific diagnostic tools
- Novel therapies: Investigating new treatments for hemangiomas and associated anomalies
- Long-term outcomes: Conducting longitudinal studies to better understand the natural history and long-term prognosis
- Risk stratification: Developing tools to predict which patients are at highest risk for complications
As research progresses, it is hoped that improved understanding of PHACE syndrome will lead to more targeted therapies and better outcomes for affected children.
PHACE Syndrome in Children
- What does the acronym PHACE stand for in PHACE syndrome?
Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects, Eye abnormalities - Which gender is more commonly affected by PHACE syndrome?
Females - What is the characteristic cutaneous feature of PHACE syndrome?
Large, segmental facial hemangiomas - Which area of the brain is most commonly affected in PHACE syndrome?
Posterior fossa - What is the most common cardiac defect associated with PHACE syndrome?
Coarctation of the aorta - Which ocular abnormality is frequently seen in PHACE syndrome?
Persistent fetal vasculature - What is the most common arterial anomaly in PHACE syndrome?
Dysplasia or narrowing of the internal carotid artery - At what age do the cutaneous hemangiomas typically appear in PHACE syndrome?
Within the first few weeks of life - Which imaging modality is most useful for diagnosing brain and vascular anomalies in PHACE syndrome?
Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) - What is the risk of stroke in children with PHACE syndrome?
Increased risk due to cerebrovascular anomalies - Which endocrine abnormality is associated with PHACE syndrome?
Hypothyroidism - What is the first-line treatment for problematic hemangiomas in PHACE syndrome?
Oral propranolol - Which cranial nerve dysfunction is commonly seen in PHACE syndrome?
Horner syndrome - What is the long-term prognosis for children with PHACE syndrome?
Variable, depending on the severity of associated anomalies - Which cardiac imaging technique is recommended for children with PHACE syndrome?
Echocardiography - What is the significance of sternal defects in PHACE syndrome?
Associated with intracardiac hemangiomas - Which subtype of PHACE syndrome involves only cutaneous hemangiomas and posterior fossa anomalies?
PHACE syndrome without extracutaneous manifestations - What is the role of systemic corticosteroids in treating hemangiomas in PHACE syndrome?
Second-line treatment when propranolol is contraindicated or ineffective - Which respiratory complication can occur in PHACE syndrome due to subglottic hemangiomas?
Airway obstruction - What is the recommended frequency of neuroimaging follow-up in PHACE syndrome?
Annually or more frequently if clinically indicated - Which genetic testing is recommended for children with PHACE syndrome?
Currently, no specific genetic test is available for PHACE syndrome - What is the risk of developmental delay in children with PHACE syndrome?
Increased risk, particularly in those with significant brain anomalies - Which subspecialists are typically involved in the multidisciplinary care of PHACE syndrome?
Dermatology, neurology, cardiology, ophthalmology, and otolaryngology - What is the significance of midline ventral defects in PHACE syndrome?
Associated with an increased risk of structural brain anomalies - Which vascular malformation can mimic PHACE syndrome?
Sturge-Weber syndrome - What is the role of laser therapy in treating hemangiomas in PHACE syndrome?
Used for residual cutaneous lesions after involution - Which growth parameter is often affected in infants with PHACE syndrome?
Head circumference - What is the recommended ophthalmological follow-up for children with PHACE syndrome?
Regular examinations to monitor for amblyopia and other ocular complications - Which cerebrovascular anomaly in PHACE syndrome increases the risk of moyamoya syndrome?
Progressive narrowing of the internal carotid arteries
