Sturge-Weber Syndrome Awareness day
Posted on June 21, 2015
June 27th . . . the 178th day of the year.
In history, it is denoted as a day when the world’s first ATM was installed in a northern London borough; the day Greece officially joined World War I with the Allied Powers; the day Mohammed Ali announced that his third retirement would be permanent (it wasn’t); the day the first film to star James Moore as British Secret Agent, James Bond, was released in theaters to excellent reception; the day when the normally arctic-like state of Alaska reached its record-breaking temperature of 38°C; the day that sparked the “Football War”, after El Salvador dissolved diplomatic relations with Honduras following their FIFA World Cup match. Like every other date on the 365-day calendar, June 27th has its fair share of notable births, deaths, as well as historical events.
It is also Sturge-Weber Syndrome Awareness Day.
Perhaps you are a multiple PhD holder; perhaps you have excessive experience with, or extensive knowledge of, the most rare human maladies and diseases in existence. But you also might be requesting a brief reminder of what Sturge-Weber Syndrome is . . . or, indeed, an introduction to what it is. And it is for precisely this purpose that Awareness Days are so helpful: to give daily reminders (or introductions) of the uncommon and sometimes unheard of, but no less important, syndromes afflicting thousands of people throughout the world.
Occurring approximately once in 200,000 births, Sturge-Weber Syndrome (SWS) is a rare congenital, neurological, and skin disorder. The preliminary symptom of SWS includes a characteristic port-wine stain on the face or head, noticeable at birth. In Type I SWS, neurological abnormalities arise from the malformation of blood vessels in the membranes surrounding the brain. Epileptic seizures begin in infancy, and often worsen with age. Most patients also develop glaucoma and visual impairment in one eye, migraine headaches, and cognitive decline leading to mental retardation. Frequently, only one side of the face displays the port-wine stain, while one side of the brain, opposite the port-wine stain, is affected by seizures.
Sturge-Weber Syndrome is caused by somatic mosaic mutations within GNAQ, a gene which would normally function by binding G proteins for the regulation of signal transduction cascades. Supported through whole-genome sequencing of both affected and unaffected tissue from patients with SWS, it was found that a single nucleotide variant on GNAQ resulted in the disorder. Alternative GNAQ mutations concerning different residue substitutions explain the prevalence of varying severities of the disease.
It is thought that a guanine residue in affected somatic cells is replaced with a leucine residue, essentially mutating the physio-chemical properties of the cell from polar to hydrophobic. This Gln209Leu mutation leads to overactivation of the mitogen-activated protein kinase (MAPK) pathway via increased downstream signaling. High MAPK activity increases cell proliferation and inhibits programmed cell death; ultimately, overactivity of this pathway is thought to cause the excessive and malformed blood vessels seen in Type I Sturge-Weber syndrome.
Alternately, an arginine residue substitution for glutamine (Arg183Gln) mutates the physio-chemical properties of the cell from basic to hydrophilic. This mutation does not have as severe effects on signaling activity as that of Gln209Leu; rather, it is thought to contribute to nonsyndromic port-wine stains. Thus, the facial birthmark characteristic of Type II Sturge-Weber syndrome is the extent of the symptoms, with neither seizures nor mental disabilities afflicting the patient.
Thus, Type I SWS is drastically more severe—and also more common—than Type II. While both Types display the port-wine stain, only Type I is affiliated with epileptic seizures and mental retardation. The clinical course for treatment of Type I SWS is highly variable, with less than 25% of patients responding to anticonvulsant medication. In cases where anticonvulsants are ineffectual, surgery may be necessary to remove the affected parts of the brain. However, following a full hemispherectomy, mild seizures often persist. There is no complete treatment for the resulting development disability and mental retardation.
Treatment for Type II SWS is not always necessary, as there is little interference with cognition apart from possible headaches. However, laser treatment can be used to lighten the port-wine stain, and a drug can be prescribed to reduce the incidence of glaucoma.
A vast selection of anticonvulsants are available to control the epileptic seizures of Type I SWS. From Ativan® to Lamictal®, from Topamax® to Felbatol®, from Vimpat® to Stavzor®, selecting the best drug to effectively treat the patient remains a serious and time-consuming problem. At Heurolabs, we envision a system that will support both physicians and patients by providing visualized information of expected side effects, effectiveness of treatment combinations, and efficacies of the patient’s lifestyle, while also providing the relevant data in a summarized and quickly accessible format. It is our goal to optimize the sporadic, incomplete, or otherwise ineffectual treatment for epileptic seizures in cases like Type I SWS, where neither time nor the patient’s well-being is a luxury, but rather a necessity. At Heurolabs, we seek to improve our understanding of epileptic seizures, to spread awareness of some of the rarest syndromes of which it is a major symptom, and to optimize seizure treatments in hopes to best support patients and their families.
What are we doing about this?
Our team is currently hard at work gathering data and building models focusing on epilepsy and anticonvulsant drugs. One of the key promises of Artificial Intelligence and Machine Learning is the one where we use these technologies in order to process complex data sets to discover new insights. Our first milestone is to help epileptologists in the process of selecting a therapy. A process we have come to learn takes up 2 years before an effective combination is found. Orphaned diseases often get very little resources especially in research, and this is why we must embrace advanced technology.
There are no limits to human ingenuity and one day we will find a cure for every disease there is. Whether it is genetic re-programming or stem cells or yet-to-be-named technique. We believe that human ingenuity can overcome the hardest of obstacles and once we have put our minds and hearts to achieve a goal, it can be achieved. This passion for life is what inspires our team on our journey to create technology for a better life.
Do you know someone living with SWS? Tell the world what is it like
We developed an audio app where people can anonymously share in their own voice how they feel , what they wish for, what are the hardest things they have to endure. The application is called ‘Sonic’ and is available via the web or as a mobile application for Android or iOS.
We believe that 1 in 200,000 is 1 too many.
Here’s to June 27th, the 178th day of the year (179th in leap years!). Here’s to those who endure and those who support them get through the days.
Shirley, Matthew D., et al. “Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ.” New England Journal of Medicine 368.21 (2013): 1971-1979.