Introduction: Ehlers-Danlos syndrome is a well classified connective tissue disorder recognized by its features of hyperextensibility of joints and hyperelasticity of the skin. However, the rare vascular type (Ehlers-Danlos type IV) is more difficult to identify in the absence, rarity, or subtlety of the classical physical features. Patients presenting to the emergency department (ED) with acute complications of vascular Ehlers-Danlos syndrome may be critically ill, requiring accurate diagnosis and tailored management.

Case Report: This report details a case of spontaneous innominate artery pseudoaneurysm rupture in a pediatric patient with previously undiagnosed Ehlers-Danlos syndrome. Initial ED evaluation was followed by urgent operative intervention and subsequent genetic testing to confirm final diagnosis.

Conclusion: Due to its high morbidity and mortality, vascular type Ehlers-Danlos syndrome should be considered in the differential for otherwise unexplained spontaneous vascular injury.

Ehlers-Danlos syndrome is a rarely encountered connective tissue disorder characterized by skin hyper-elasticity, joint hyper-flexibility, and vasculature fragility. We report a 41-year-old female presenting with scalp swelling following minor head trauma. The patient presented with a large cephalohematoma that despite compressive measures and Factor IX administration continued to progress, necessitating transfer for definitive surgical intervention. The patient underwent surgical evacuation of approximately 1 liter of blood, followed by drain placement and compression dressing. This case underscores the importance for emergency physicians to recognize the potential vascular catastrophes these patients may present with following even minor injury. [West J Emerg Med. 2013;14(5):419-420.]

Background

Case summary

Discussion

Hypermobile Ehlers-Danlos Syndrome (hEDS) is a condition with heterogeneous clinical features characteristic of a connective tissue disorder (CTD) including generalized joint hypermobility, hyperextensible skin, joint subluxations/dislocations and commonly associated comorbidities such as postural orthostatic tachycardia syndrome and fatigue (Castori et al., 2017; Gensemer et al., 2021). hEDS is the only one among 13 Ehlers-Danlos syndrome (EDS) subtypes without a known etiology or targeted clinical molecular genetic testing, requiring strict clinical diagnostic guidelines and exclusion of other similar conditions (Malfait et al., 2017). Possibly due to the diverse clinical symptoms and the lack of molecular confirmation, hEDS referrals for evaluation for hEDS may be increasingly inundating and overwhelming genetics clinics. This study was a retrospective chart review that analyzed 143 referrals for suspected hEDS/CTD to the University of California, Irvine (UCI) adult genetics clinic and the referring providers’ relevant medical notes, if available. The purpose of this research was to understand why medical professionals refer patients with suspected hEDS/CTD for genetic evaluation and what they document in the referral. First, a classification scheme to identify appropriate referrals was developed using a consensus process. Utilizing a system with four categories of appropriateness, 51% (N=74) of referrals were found to lack enough details to be categorized as appropriate. Additionally, features recorded in the referral documentation were analyzed, and many features related to CTD aside from joint involvements either had not been assessed or were not documented. Many referrals (>75%) also did not document the presence or absence of certain CTD-related features including dislocations, subluxations, easy bruising, and elastic skin. Furthermore, the classification of appropriateness for the primary care referrals differed significantly from that for the referrals from specialist providers (χ2 (3) = 10.48, p=0.02). Referrals from primary care providers were more likely to be missing details (N=26, 47% compared to N=19, 22% for specialty referrals). The findings suggest that educational outreach to referring providers and implementing a referral protocol may help improve the quality of referrals and, ultimately, for genetics clinics to be able to provide optimal support to patients suspected with hEDS/CTD and the providers involved in their medical journeys.

Background

Objective

Participants and setting

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Results

Conclusions

Tenascin-X is an extracellular matrix protein initially identified because of its overlap with the human CYP21B gene. Because studies of gene and protein function of other tenascins had been poorly predictive of essential functions in vivo, we used a genetic approach that critically relied on an understanding of the genomic locus to uncover an association between inactivating tenascin-X mutations and novel recessive and dominant forms of Ehlers-Danlos syndrome. Tenascin-X provides the first example of a gene outside of the fibrillar collagens and their processing enzymes that causes Ehlers-Danlos syndrome. Tenascin-X null mice recapitulate the skin findings of the human disease, confirming a causative role for this gene in Ehlers-Danlos syndrome. Further evaluation of these mice showed that tenascin-X is an important regulator of collagen deposition in vivo, suggesting a novel mechanism of disease in this form of Ehlers-Danlos syndrome. Further studies suggest that tenascin-X may do this through both direct and indirect interactions with the collagen fibril. Recent studies show that TNX effects on matrix extend beyond the collagen to the elastogenic pathway and matrix remodeling enzymes. Tenascin-X serves as a compelling example of how human experiments of nature can guide us to an understanding of genes whose function may not be evident from their sequence or in vitro studies of their encoded proteins.

Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders (CTDs) characterized by hyperflexibility, skin hyperextensibility, and tissue fragility. As recently as 2017, the International EDS Consortium published a new classification system with diagnostic criteria for thirteen different subtypes of EDS [Malfait et al., 2017]. The genetic etiology is known for all subtypes except hypermobile EDS (hEDS) which relies on clinical diagnostic criteria for diagnosis. Many patients are referred to the Genetics specialty for evaluation for EDS or other possible CTD. This study consisted of a retrospective chart review of referrals and Genetics consultation notes at one adult Genetics clinic to determine what types of providers are referring patients to the Genetics specialty, what types of evaluations (either imaging or evaluations by other specialties) patients are undergoing prior to seeing Genetics to further clarify if they may have a possible CTD, and what recommendations Genetics is making for these patients following evaluation. This study also compared patients who were self-referred and those who were referred by a provider and found there was no difference in the number of evaluations done prior to seeing Genetics nor the recommendations made after seeing Genetics. This study demonstrated that there is value in a Genetics evaluation for EDS or other CTDs because patients are discussing more clinical features with Genetics providers, geneticists provide a comprehensive exam across all systems of the body, and genetic counselors are uniquely qualified to provide supportive counseling, education, and resources this patient population needs.