Vascular-type Ehlers-Danlos syndrome caused by a hitherto unknown genetic mutation: a case report

Abstract

IntroductionVascular-type Ehlers-Danlos syndrome is an autosomal dominant disease that causes arterial spurting, intestinal perforation, uterine rupture and hemopneumothorax due to decreased production of type III collagen. The average age at death is 48 years old, and it is considered to be the most severe form of Ehlers-Danlos syndrome. We report the case of a 64-year-old Japanese woman and her 38-year-old daughter who were diagnosed with this disease.Case presentationA 64-year-old Japanese woman was referred to our hospital because of right anterior chest pain following cough and pharyngeal discomfort. Pleurisy was suspected due to the presence of right pleural effusion, so the next day she was referred to our department, where a detailed examination led to the diagnosis of hemothorax. The bleeding that caused the right hemothorax was difficult to control, so our patient was transferred to the Department of Thoracic Surgery for hemostasis control. Our patient’s personal history of uterine hemorrhage and skin ulcers, as well as the finding of skin fragility during surgery, were indicative of a weak connective tissue disease; therefore, after improvement of the hemothorax, a genetic analysis was performed. This revealed a heterozygous missense mutation in COL3A1, c.2411 G>T p.Gly804Val (exon 36). A detailed investigation conducted at a later date revealed that her daughter also had the same genetic mutation. This led to the diagnosis of vascular-type Ehlers-Danlos syndrome characterized by a new gene mutation.ConclusionWe report a new genetic mutation associated with vascular-type Ehlers-Danlos syndrome. We present the clinical and imaging findings, and the disease and treatment course in this patient. We believe this information will be important in treating future cases of vascular-type Ehlers-Danlos syndrome in patients with this mutation.

Urogenital and pelvic complications in the Ehlers‐Danlos syndromes and associated hypermobility spectrum disorders: A scoping review

“…Table summarizes the design and publication date characteristics of the 105 included studies . Studies consisted of case reports/series (N = 62, 60%) and observational studies (N = 43, 40%), including cross sectional (N = 29), case‐controlled (N = 12), and cohort (N = 2) designs.…”

Spontaneous pneumothorax and hemothorax frequently precede the arterial and intestinal complications of vascular Ehlers–Danlos syndrome

“…The body of literature regarding pulmonary complications in vEDS consists of case reports (Abrahamsen, Kulseth, & Paus, ; Dar, Wani, Mushtaque, & Kasana, ; Gu et al, ; Ishiguro et al, ; Kashizaki, Hatamochi, Kamiya, Yoshizu, & Okamoto, ; Omori et al, ; Sadakata et al, ; Selim, Lane, Rubinowitz, & Siner, ). The majority of these case reports include males with an average age of 24 years (range 11–64) at presentation, not unlike the mean age of initial P/HTX presentation in our cohort.…”

Selected Case From the Arkadi M. Rywlin International Pathology Slide Series

“…144,145 Four major (skin hyperextesibility, widened atrophic scarring, joint hypermobility, and positive family history) and minor diagnostic criteria have been identified to clinically establish the EDS diagnosis. 145,146 Six major types of EDS have been classified, classic (type 1 and 2), hypermobility (type 3), vascular (type 4), kyphoscoliosis (type 6), arthrochalasia (type 7A-B), and dermatosparaxis (type 7C). 144,145 The classification is based on the clinical and corresponding molecular pathogenetic findings in collagen types I, III, and V, or processing enzymes, with the category clinical descriptor capturing the pathognomonic manifestation of each type.…”

“…Lungs can be affected by EDS, and most cases are of the vascular type. Vascular type or type 4 EDS is caused by mutations of type III collagen (COL3A1) gene, 146 and is considered a clinically dramatic form because of blood vessel fragility. Experimental studies have demonstrated the extreme sensitivity of Col3a1-insufficient mice to prematurely develop thoracic aortic ruptures in response to angiotensin II and its associated high levels in high blood pressure conditions.…”