Physical and Family History Variables Associated With Neurological and Cognitive Development in Sturge-Weber Syndrome

Abstract

Background: Sturge-Weber syndrome (SWS) is caused by a somatic mutation in GNAQ leading to capillary venous malformations in the brain presenting with various neurological, ophthalmic, and cognitive symptoms of variable severity. This clinical variability makes accurate prognosis difficult. We hypothesized that the greater extent of physical factors (extent of skin, eye, and brain involvement), presence of possible genetic factors (gender and family history), and age of seizure onset may be associated with greater symptom severity and need for surgery in patients with SWS. Methods:The questionnaire was collected from 277 participants (age: two months to 66 years) with SWS brain involvement at seven US sites.Results: Bilateral brain involvement was associated with both learning disorder and intellectual disability, whereas port-wine birthmark extent was associated with epilepsy and an increased likelihood of glaucoma surgery. Subjects with family history of vascular birthmarks were also more likely to report symptomatic strokes, and family history of seizures was associated with earlier seizure onset. Learning disorder, intellectual disability, strokelike episodes, symptomatic stroke, hemiparesis, visual field deficit, and brain surgery were all significantly associated with earlier onset of seizures. Conclusion:The extent of brain and skin involvement in SWS, as well as the age of seizure onset, affect prognosis. Other genetic factors, particularly variants involved in vascular development and epilepsy, may also contribute to neurological prognosis, and further study is needed.

Study protocol: retrospectively mining multisite clinical data to presymptomatically predict seizure onset for individual patients with Sturge-Weber

“…A family history of seizures or epilepsy is associated with an early age of seizure onset in SWS. 136 This suggests that genetic factors, beyond the underlying somatic mutation in GNAQ , have a role in determining the timing of seizure onset in SWS. 1 The extent of skin involvement with PBW may also be a prognostic factor.…”

“…Whether gender impacts the early evolution of SWS as manifested in neuroimaging remains to be studied. A family history of seizures or epilepsy is associated with an early age of seizure onset in SWS 136. This suggests that genetic factors, beyond the underlying somatic mutation in GNAQ , have a role in determining the timing of seizure onset in SWS 1.…”

Sturge–Weber Syndrome and Glaucoma

“…According to Day et al .,[ 3 ] the children with worst prognostic factors with SWS brain and skin involvement should be managed to prevent seizures and stroke. According to Comi,[ 4 ] continued safe screening methods should be utilized to detect presymptomatic brain and eye involvement.…”

Quality of Life in Children With Sturge-Weber Syndrome

“…The largest study on SWS to date found that males with SWS that experienced seizure onset at age less than or equal to 6 months were more likely to experience stroke-like episodes. 16 Sex-related differences have been extensively studied outside the SWS literature. In terms of stroke, males are more likely to experience ischemic episodes at a younger age.…”