Abstracts

The genetic basis, pathophysiology, and spectrum of Sturge-Weber Syndrome (SWS) remain unknown. Epilepsy in SWS presents by age 5 years in 95% of cases (range 0-23 years). The vast majority of cases are felt to be sporadic, without any affiliated family history. We present an individual affected with SWS with an atypically late onset of epilepsy. Furthermore, he is one member of a pedigree in which several relatives exhibit vascular (including port wine) cutaneous lesions. Clinical evaluation of the proband was performed and detailed pedigree information was obtained during inpatient and outpatient contacts at our Comprehensive Epilepsy Program. Clinical investigations included EEG, MRI [plusmn] gadolinium, MRA and diffusion-weighted imaging (DWI). A 48-year-old male with a congenital facial port wine stain (left V1 distribution) presented with a generalized tonic-clonic seizure and treatment was begun. He re-presented weeks later with focal status epilepticus, complicated by an ipsilateral occipital ischemic stroke evident with DWI. Imaging revealed calcifications in his left hemisphere with gadolinium enhancement consistent with leptomeningeal angiomatosis and he was diagnosed with SWS. He also reported a family history of vascular cutaneous lesions. These were present in his daughter (cervical region), mother (cervical region) and maternal grandmother (arm and breast). None of his family reported epilepsy or glaucoma. SWS has not yet been shown to obey familiar Mendelian genetics. Although one family with SWS in both a father and son has been reported (Adamczak 1979), virtually all cases are sporadic. Somatic mosaicism has been proposed as one possible pathophysiologic mechanism in SWS (Happle 1987). Studies on fibronectin expression in fibroblasts from SWS patients (port wine vs. normal skin) are consistent with a somatic mosaic mechanism. Chromosomal analyses of port wine vs. normal cells have found other markers of mosaicism. Familial Port Wine Stain without epilepsy has been described in one kindred with unclear inheritance pattern (Berg et al 2000). Our proband met clinical criteria for the diagnosis of SWS. His positive family history of cutaneous vascular lesions with a possible autosomal dominant inheritance pattern and atypically late expression of epilepsy are distinctive features. This unique kindred with members expressing cutaneous vascular lesions alone or SWS suggests that these conditions may share a common genetic mechanism. One may interpret this kindred as an instance of hereditary Port Wine Stain, (with one member additionally displaying features of SWS) or as a kindred with hereditary SWS with phenotypic heterogeneity. Somatic mosaicism may provide one possible explanation for the inconsistent expression of cerebral abnormalities in this kindred. Future collaborative studies using this kindred may provide insights into the molecular genetic basis of this uncommon cause of epilepsy.