top of page

Diving deeper into orphan diseases - Williams-Beuren Syndrome (WBS)

With this article we are continuing with our series focusing on orphan diseases, and today we’ll be looking at Williams-Beuren syndrome (WBS) also known as Williams syndrome.

Disclaimer: This article only reviews some of the known facts of Williams-Beuren syndrome, if you are looking for more in-depth information or support for Williams-Beuren syndrome please visit here: Williams Syndrome Association | (


WBS is a complex condition that has a set of unique symptoms that affect an individual’s cognitive and physical development. The disorder only occurs in roughly 1 out of every 7,500 people. Potentially due to its rarity, WBS is often undiagnosed or misdiagnosed and can cause parents, doctors, and teachers to have difficulty meeting the unique needs of an individual with WBS. While it can be dangerous in the early years for a WBS patient, they have the potential to live well into adulthood. A WBS patient has an estimated life span of 10-20 years less than the average person, but a formal assessment of life expectancy does not currently exist. This shorter than average lifespan is largely attributed to a malformed cardiovascular system, causing many WBS patients to experience, among others, arterial stenosis.

What is WBS?

WBS is a rare genetic multisystemic neurodevelopmental disorder that is characterized by cardiovascular anomalies. These anomalies are attributed to a contiguous gene deletion of the Williams-Beuren syndrome critical region (WBSCR) that encompasses the elastin gene (ELN). The deletion causes WBS patients to produce only around half of the elastin that a healthy person does, leading to a destabilized extracellular matrix structure affecting the elasticity and stability of different tissues and blood vessels, affecting, among others, the proper function of the cardiovascular system. This lack of structure leads to systemic cardiovascular issues that are very threatening to a WBS patient throughout their life, and it is of particularly noticeable concern in the first 5 years of a patient’s life. If left untreated, WBS patients can develop ventricular hypertrophy and eventually experience ventricular failure. Furthermore, the risk of sudden death in WBS is 25 to 100 times greater than the age-matched general population. Some of the causes of death in these cases remain unknown, but many of them have been attributed to coronary artery stenosis. However, cardiac anomalies are not the only characteristic sign of WBS. WBS patients also have high rates of mild to moderate intellectual deficits and a characteristic cognitive profile that comes with a very outgoing and friendly personality.

What are symptoms of WBS?

WBS is denoted by several multisystemic symptoms. These symptoms commonly include a variety of cardiovascular problems and endocrine issues. Cardiovascular problems are present in 80% of individuals with WBS, and the most common manifestations of these problems are aortic stenosis, pulmonary stenosis, coarctation, and Supravalvar Aortic Stenosis (SVAS). The cardiovascular problems are directly traced to the lack of elastin present in a WBS patient’s body, as their cardiovascular system lacks the necessary structure that elastin provides. In addition to having these structural issues,

Williams-Beuren-Syndrome facial features
Image from Cleveland Clinic, depicting WBS facial features.

WBS patients can have heightened levels of calcium in their bloodstream due to a malfunctioning endocrine system. It is more common for infants with WBS to have heightened calcium, but it is a condition that can occur at any point in a patient’s life. High blood calcium symptoms in infants can include irritability, constipation, or vomiting and symptoms in older patients can include abdominal pains, fatigue, and frequent urination. Some of the other common symptoms that can accompany a WBS patient but are not as immediately threatening to a patient’s wellbeing include distinctive facial features, cognitive challenges, delayed development, short stature, auditory anomalies, dental anomalies, sleep disorders, scoliosis, feeding difficulties, gastrointestinal problems, and urinary tract malformation. No single individual will experience the full range of symptoms, but it is common for WBS patients to experience several of these symptoms.

How is WBS inherited?

WBS is caused by the deletion of 26-28 genes on one copy of Chromosome 7q11.23 in a contiguous gene deletion of WBSCR including the elastin gene, ELN. This deletion of the ELN gene causes a WBS patient’s body to contain around half of the elastin that a normal person’s body contains. The fact that WBS is caused by contiguous gene deletion means that most people with WBS have not inherited the condition from one of their parents. WBS is an autosomal dominant inherited condition. This means that people with WBS have a strong potential to pass down WBS to their children with a 50% chance.

How is WBS Diagnosed?

WBS is usually diagnosed through a combination of a physical examination, a cardiovascular examination, and then using genetic testing to confirm the diagnosis. Physicians screen for the recurrent 7q11.23 contiguous gene deletion of the Williams-Beuren syndrome critical region (WBSCR) that encompasses the elastin gene (ELN). If physicians can confirm the 7q11.23 contiguous gene deletion the patient is diagnosed with WBS.

Treatments and Outlook

WBS is a condition that needs to have a multidisciplinary lifelong approach to treatment with close medical monitoring, professional anticipatory guidance, direct therapies, pharmacotherapy, and surgery. Especially close cardiac follow-up during the first year of life and close monitoring of serum calcium during the first two years of life is strongly recommended. There must also be extensive and careful preoperative and postoperative planning for any WBS patient due to the increased risk of cardiovascular complications.

Currently the treatments for WBS only serve to mitigate the symptoms. Our technology platform, DESTiNED would also fall into this category of symptom mitigation. DESTiNED would be able to provide the targeted delivery of PGG molecules to a patient’s blood vessels with the goal of restoring the vessels’ elasticity. In addition, DESTiNED could potentially stabilize a patient sufficiently enough to prevent deterioration and may even allow arteries to remodel with the growth and development of the patients if the therapy was started early in childhood. Moreover, Elastrin is currently working on the de novo synthesis of elastin using synthetic mRNA coding for Tropoelastin (TE). A new, highly innovative, and promising drug in the Elastrin Therapeutics pipeline for tissue engineering. This drug is designed to help treat the insufficient amount of elastin in WBS patients, caused by the gene deletion.

At Elastrin Therapeutics, we will attempt to supplement the missing elastin amount via mRNA using the DESTiNED platform for the targeted delivery and thereby provide the information to newly produce and hopefully replace missing elastin.




bottom of page