College Life: Case Studies of Ehlers-Danlos Syndrome

*Written by Misti Blu Day McDermott in Epidemiology class for Biomedical Science Bachelors program.

Case Studies: Ehlers-Danlos Syndrome Manifestations

Case-control studies are similar to epidemiological studies as they both document and analyze precise measurements of a disease. Case-control studies are preferred when: exposure data is difficult or too expensive to obtain, the disease is rare, the disease has a long induction and latent period, little is known about the disease, and the underlying population is dynamic (Aschengrau & Seage, 2014).

Hypermobility Ehlers-Danlos Syndrome (hEDS) is one of thirteen subtypes of Ehlers-Danlos Syndrome, and the most common. However, hEDS is the only subtype that is not yet linked to a specific genetic mutation. EDS is a connective tissue disorder, making it a multisystemic disorder. This under-recognized disorder can result in manifestations such as cardiovascular, gastrointestinal, hematologic, ocular, gynecologic, neurologic, autonomic nervous system, and orthopedic (joint dislocations), to list a few (Gazit, 2014). Because of the nature of this disorder, misdiagnosis is common or due to the hyperfocus of particular issues rather than the patient as a whole. This results in negligence of these patients, leading to severe disabilities and mismanaged health in which could have been avoided or minimized.

It is critical to rule out other connective tissue disorders such as Marfan, Loeys-Dietz syndrome, and the more severe subtype, vascular EDS (vEDS), as these disorders have catastrophic manifestations. Vascular complications are also observed in other EDS subtypes. In a study by D’hondt et al (2018), data was collected from 467 patients; 77 presented with a vascular phenotype. Hematomas, arterial dissections, hemorrhages, as well as minor vascular complications were noted. Though life threatening vascular complications are rare in the “nonvascular” subtypes, it is still possible to occur. It should be noted that the criteria for this study did exclude hypermobile EDS since the genetic etiology is still unknown. A new study should be presented once hEDS becomes linked to a known gene, since hEDS is the most common type.

A recent study by Ritelli et al (2020) examined patients’ cohort and evaluated clinical features of EDS. The study was done over 2010-2019 of 75 patients, 44 index-cases, and 31 relatives with classical EDS (cEDS) at the Spedali Civili University Hospital of Brescia. This subtype is more associated with atrophic scars, marked skin hyperextensibility, and other skin manifestations. The cEDS patients’ molecular analysis was performed on exons and intron-flanking regions of COL5A1, COL5A2, and exon 14 of COL1A1 with PCR amplification and Sanger sequencing.  

Ehlers-Danlos Syndrome has a long list of overlapping comorbidities of multisystemic involvement in each subtype, though each subtype has additional distinguishing features. Ehlers-Danlos Syndrome requires additional and ongoing studies in order to better understand this greatly misunderstood disorder. Patients are relying on medical breakthroughs, potential genetic therapy, faster diagnostic recognition and understanding, and better management of symptoms as a whole. 

References:

Aschengrau, A., & Seage, G. R. (2014). Essentials of epidemiology in public health. 3rd ed. Burlington, MA: Jones & Bartlett Learning.

D’hondt, S., Van Damme, T., & Malfait, F. (2018). Vascular phenotypes in nonvascular subtypes of the Ehlers-Danlos syndrome: a systematic review. Genetics in medicine : official journal of the American College of Medical Genetics, 20(6), 562–573. https://doi.org/10.1038/gim.2017.138

Gazit, Y., Jacob, G., & Grahame, R. (2016). Ehlers-Danlos Syndrome-Hypermobility Type: A Much Neglected Multisystemic Disorder. Rambam Maimonides medical journal, 7(4), e0034. https://doi.org/10.5041/RMMJ.10261

Ritelli, M., Venturini, M., Cinquina, V., Chiarelli, N., & Colombi, M. (2020). Multisystemic manifestations in a cohort of 75 classical Ehlers-Danlos syndrome patients: natural history and nosological perspectives. Orphanet journal of rare diseases, 15(1), 197. https://doi.org/10.1186/s13023-020-01470-0