👤 Elizabeth Jewell

Sturge-Weber syndrome and encephalocraniocutaneous lipomatosis (ECCL) are neurocutaneous syndromes with unique presentations. A 15-month-old male presented with focal seizures that progressed to medically refractory focal epilepsy. He had no ocular or cutaneous findings. Imaging demonstrated complex, transdural leptomeningeal enhancement suspicious for pial angiomatosis. Electroencephalogram showed focal seizures from the right posterior region. Sturge-Weber syndrome without cutaneous manifestations was suspected. Following right posterior disconnection surgery, next generation sequencing of affected brain tissue confirmed a mosaic ECCL may have variable expression and should be considered in children with refractory epilepsy and an anatomical brain abnormality. Leptomeningeal enhancement is commonly found in Sturge-Weber syndrome but may be seen in other neurocutaneous syndromes, such as ECCL. Hemispheric dysplasia should raise suspicion for a neurocutaneous syndrome, even without oculocutaneous stigmata. Genotype-guided diagnostics for patients with atypical findings may facilitate targeted postsurgical management and lifetime surveillance. Show less

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation. Show less