Port-wine Birthmarks and Sturge-Weber Syndrome: The Challenge of Diagnosis and Management

Despite recent advances in our understanding of port-wine birthmarks and the related Sturge-Weber syndrome, the diagnosis and management of these conditions remain challenging.  In the September issue of Pediatrics in Review, Anna Poliner and colleagues provide a useful update of the management of port-wine vascular lesions and discuss the relationship of these lesions to Sturge-Weber syndrome.¹

The once confusing nomenclature of cutaneous vascular lesions was clarified in 1982, when Mulliken and Glowacki proposed that vascular birthmarks be classified as either malformations or hemangiomas based on their cellular features and clinical course.²  Vascular malformations are present from birth, expand in proportion to the child’s growth, and do not regress. Hemangiomas, in contrast, may or may not be visible at birth. They typically expand rapidly before eventually involuting.  Vascular malformations have normal endothelial cell turnover, while hemangiomas exhibit increased endothelial cell activity during the proliferating phase. 

A port-wine vascular malformation is present at birth. Its boundary expands in proportion to the child’s growth, although the lesion often becomes thicker by adulthood. Sturge-Weber syndrome is characterized by an upper facial port-wine lesion, an intracranial leptomeningeal vascular lesion, and the variable occurrence of glaucoma. About 85% of the individuals with a forehead port-wine nevus do not have an intracranial vascular malformation and thus never experience neurological symptoms, although some of these patients nevertheless develop glaucoma. Children without an upper face or eyelid nevus have little likelihood of having an intracranial vascular malformation and thus do not develop neurological complications.³ Historically, the forehead location of the nevus in individuals with Sturge-Weber syndrome was linked to the area’s cutaneous nerve supply by the ophthalmic division of the trigeminal nerve, but this odd notion has finally been discounted in favor of a purely vascular explanation.

While neurofibromatosis, tuberous sclerosis, and other neurocutaneous disorders have well-recognized inheritance patterns, port-wine nevi and Sturge-Weber syndrome occur sporadically. In 1987, Rudolf Happle suggested that the sporadic pattern of Sturge-Weber syndrome and other sporadic conditions could result from a post-conception somatic mosaic mutation.⁴ Some twenty-six years later, Shirley et al. confirmed with skin tissue analyses that port-wine nevi result from somatic mosaicism of GNAQ on chromosome 9q21.2.⁵ Mutation testing of blood specimens is not generally useful for somatic mosaic conditions, and since GNAQ mutations are responsible for both isolated port-wine lesions and Sturge-Weber syndrome, the presence of a mutation does not predict the phenotype.

Among people with Sturge-Weber syndrome, the neurological manifestations are highly variable. Most individuals are neurologically normal at birth, then experience seizures at a few months of age, often in conjunction with a febrile illness. Some children respond well to antiseizure medications, while others develop medically and sometimes surgically intractable epilepsy. Intellectual dysfunction is common but by no mean universal. Children whose seizures begin after age two years and those whose early seizures were promptly controlled tend to have fewer cognitive deficits, making early diagnosis of the syndrome and prompt seizure treatment vitally important.⁶

A port-wine nevus is obvious at birth, so the pediatrician must be prepared to address the family’s concerns and decide how to evaluate the child for other manifestations. Families can be reassured that relatives are unlikely to develop the syndrome. Not all babies with a forehead port-wine nevus develop neurological complications. Glaucoma may be present at birth or develop later, and its timely recognition and treatment is essential. Because of the tendency for the nevus to thicken over time, pulsed dye laser therapy is often more effective when begun early.

Confirmation of brain involvement prior to the onset of seizures requires neuroimaging, but the timing of the procedure is debated. Abnormal leptomeningeal vessels can be less evident in neonates undergoing magnetic resonance imaging, leading some physicians to defer imaging until one year of age. However, seizures typically begin well before age one year, and early confirmation of intracranial involvement facilitates planning for seizure management. In other conditions, earlier seizure treatment, perhaps starting even before the onset of clinical seizures in high-risk individuals, can lessen cognitive impairment and possibly reduce the severity of subsequent epilepsy.⁷ Asking a family to wait anxiously for months until the onset of seizures seems harsh, especially when so many children with a port-wine nevus never develop neurological complications.

*Above image from: Progression of a port-wine birthmark. Adult showing increased violaceous discoloration, thickening, and the development of vascular blebs. 10.1542/pir.2021-005437

References:

1. Polinar A, Fernandez Faith E, Blieden L, Kelly KM, Metry D. Port-wine birthmarks: update on diagnosis, risk assessment for sturge-weber syndrome, and management (in press). Pediatr Rev. 2022;43(9):507–514
2. Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg. 1982;69(3):412–422
3. Enjolras O, Riche MC, Merland JJ. Facial port-wine stains and Sturge-Weber syndrome. 1985;76(1):48–51
4. Happle R. Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J Am Acad Dermatol. 1987;16(4):899–906
5. Shirley MD, Tang H, Gallione CJ et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013;368(21):1971–1979
6. Bodensteiner JB, Roach ES. Sturge-Weber Syndrome, Second Edition. Mt. Freedom, NJ: Sturge-Weber Foundation, 2010
7. Kotulska K, Kwiatkowski DJ, Curatolo P et al. Prevention of epilepsy in infants with tuberous sclerosis complex in the EPISTOP trial. Ann Neurol. 2021;89(2):304–314