By: Catherine Joachin
What is Williams Syndrome?
Williams syndrome, sometimes referred to as Williams-Beuren syndrome, is a genetic disorder brought on by the absence of chromosome number 7 genes, a deletion that occurs during fetal development (Cleveland Clinic). This genetic mutation has been associated with the evolution of various anomalies including narrow blood vessels, high blood pressure, elevated blood calcium levels, and pronounced bodily features such as unusual teeth spacing, a small jaw, flexible joints, and short stature (Cleveland Clinic). This condition is also characterized by cardiovascular defects as well as developmental and social difficulties, which is highlighted by studies demonstrating that individuals with William’s syndrome have a hard time appropriately engaging in social interaction (Davies et al. 1998; Frigerio et al., 2006).
Genetic testing, an echocardiogram, and blood testing can be used to identify gene and cardiac anomalies in suspected Williams syndrome populations (Cleveland Clinic). However, other neurodevelopmental disorders such as fetal alcohol syndrome or DiGeorge syndrome should be considered as differential diagnoses (Wilson & Iverson, 2022).
Symptoms of Williams Syndrome
People with Williams syndrome may experience a diversity of symptoms including learning and intellectual disability, farsightedness, and musculoskeletal abnormalities (e.g. scoliosis and/or an unusual gait) (Mount Sinai, n.d.). In terms of mental capacities, noticeable impairments in visual motor skills, high levels of non-social anxiety, the presence of phobias, and a shorter attention span are recurrent characteristics in affected individuals (Wilson & Iverson, 2022).
A study (Soares et al., 2013) examining the behavior of institutionalized children suggests that individuals with William’s syndrome present distinctive social-emotional and behavioral features. Hypersociality, excessive empathy, and social inhibition are frequently observed in individuals with this condition, with a smaller subset engaging in autism spectrum disorder-related behaviors to boot (Morris, 1999; Wilson & Iverson, 2022).
Risk factors of having Williams Syndrome
Williams syndrome is unpreventable. The genetic change that engenders this condition is either inherited from one of the fetus’ parents or spontaneously develops in utero. The likelihood of inheriting this disorder when a carrier is affected by this mutation is 50% (Mount Sinai, n.d.).
Individuals who present a combination of intellectual disability, poor visuospatial construction, cardiovascular difficulties, and physical abnormalities in terms of growth and facies are more likely to be suspected of having Williams syndrome (Wilson & Iverson, 2022).
Treatment options
There is no cure for Williams syndrome. Instead, early intervention programs and various forms of therapy are used to improve specific skills such as verbal or developmental abilities (Mount Sinai, n.d.). Individualized behavioral counseling and medication can be prescribed for individuals with comorbid attention-deficit/hyperactivity disorder and anxiety, but these treatment options remain management-based (Morris, 1999). For heart and blood pressure-related symptoms, consulting a specialist in order to target an appropriate treatment is recommended (Cleveland Clinic).
How does Williams syndrome relate to epilepsy?
Epilepsy has been identified as a minor feature of Williams syndrome; however, with only a few cases having been reported, research can only hypothesize that an undocumented metabolic disturbance could be a plausible cause of seizure onset in studied participants (Trauner et al., 1989; Ramocki et al., 2010; Nicita et al., 2016).
Antonell and colleagues (2010) also suggest that deletions of specific Williams syndrome region genes might be responsible for the neurological impairments observed in afflicted people. In fact, variants of the GTF2IRD1 gene, specifically, have been cited in cases of Williams syndrome paired with comorbid epilepsy and autistic traits, but further research is needed in order to draw more conclusive results (Cummings & Starr, 2023).
Conclusion
Williams syndrome is a condition marked by behavioral, physical, and internal abnormalities that cause a genetic irregularity. As of now, few studies have explored its direct association with epilepsy, but research hints at an underlying genetic basis for epileptiform activity in the chromosome 7 region.
References:
Antonell, A., Del Campo, M., Magano, L. F., Kaufmann, L., Martínez de la Iglesia, J., Gallastegui, F., Flores, R., Schweigmann, U., Fauth, C., Kotzot, D., & Pérez-Jurado, L. A. (2010). Partial 7q11.23 deletions further implicate GTF2I and GTF2IRD1 as the main genes responsible for the Williams–Beuren syndrome neurocognitive profile. Journal of Medical Genetics, 47(5), 312–320. https://doi.org/10.1136/jmg.2009.071712
Cleveland Clinic (2021). Williams Syndrome. Cleveland Clinic. Retrieved from: https:// www.defeatingepilepsy.org/living-with-epilepsy-series/imposter-syndrome/
Cummings, C. T., & Starr, L. J. (2023). Biallelic GTF2IRD1 variants in brothers with profound neurodevelopmental disorder: A possible novel disorder involving a critical gene for Williams syndrome. American Journal of Medical Genetics. Part A, 191(2), 332–337. https://doi.org/ 10.1002/ajmg.a.63021
Davies, M., Udwin, O., & Howlin, P. (1998). Adults with Williams syndrome. Preliminary study of social, emotional, and behavioral difficulties. British Journal of Psychiatry, 172(3), 273–276. https://doi.org/10.1192/bjp.172.3.273
Frigerio, E., Burt, D. M., Gagliardi, C., Cioffi, G., Martelli, S., Perrett, D. I., & Borgatti, R. (2006). Is everybody always my friend? Perception of approachability in Williams syndrome. Neuropsychologia, 44(2), 254–259. https://doi.org/10.1016/j.neuropsychologia.2005.05.008
Morris, C.A. (1999). Williams Syndrome. National Library of Medicine. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK1249/
Mount Sinai (n.d.). Williams syndrome. Mount Sinai. Retrieved from: https:// www.mountsinai.org/health-library/diseasesconditions/williamssyndrome#:~:text=Causes,50%25%20chance%20of%20inheriting%20it.
Nicita, F., Garone, G., Spalice, A., Savasta, S., Striano, P., Pantaleoni, C., Spartà, M. V., Kluger, G., Capovilla, G., Pruna, D., Freri, E., D’Arrigo, S., & Verrotti, A. (2016). Epilepsy is a possible feature in Williams-Beuren syndrome patients harboring typical deletions of the 7q11.23 critical region. American Journal of Medical Genetics. Part A, 170A(1), 148–155. https://doi.org/ 10.1002/ajmg.a.37410
Ramocki, M. B., Bartnik, M., Szafranski, P., Kołodziejska, K. E., Xia, Z., Bravo, J., Miller, G. S., Rodriguez, D. L., Williams, C. A., Bader, P. I., Szczepanik, E., Mazurczak, T., Antczak Marach, D., Coldwell, J. G., Akman, C. I., McAlmon, K., Cohen, M. P., McGrath, J., Roeder, E., … Stankiewicz, P. (2010). Recurrent Distal 7q11.23 Deletion Including HIP1 and YWHAG Identified in Patients with Intellectual Disabilities, Epilepsy, and Neurobehavioral Problems. American Journal of Human Genetics, 87(6), 857–865. https://doi.org/10.1016/ j.ajhg.2010.10.019
Soares, I., Belsky, J., Mesquita, A. R., Osório, A., & Sampaio, A. (2013). Why do only some institutionalized children become indiscriminately friendly? Insights from the study of Williams Syndrome. Child Development Perspectives, 7(3), 187-192.
Trauner, D. A., Bellugi, U., & Chase, C. (1989). Neurologic features of Williams and Down syndromes. Pediatric Neurology, 5(3), 166–168. https://doi.org/10.1016/0887-8994(89)90066-0
Wilson, M. & Iverson, C. B. (2022). Williams Syndrome. National Library of Medicine. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK544278/
