Ehlers-Danlos syndrome type IV with few extrathoracic findings: a newly recognized point mutation in the COL3A1 gene

Abstract

Ehlers-Danlos syndrome type IV (EDS IV) is caused by mutation within the COL3A1 gene, resulting in the disorder of type III procollagen. The diagnosis is confirmed by demonstrating the synthesis of abnormal type III procollagen molecules from cultured dermal fibroblasts or by identifying the mutation in the COL3A1 gene.The authors report a case of EDS IV caused by a novel point mutation in the COL3A1 gene in a 16-yr-old female. Recurrent haemoptysis and cavitary formation of the lung were evidence of pulmonary involvement. However, extrathoracic manifestations of EDS IV were mostly absent.To the best of the authors9 knowledge, all previously reported Ehlers-Danlos syndrome IV patients with respiratory disease had the characteristic findings or histories of Ehlers-Danlos syndrome IV. In the present case, connective tissue friability was suspected due to tissue laceration observed in the biopsied lung specimen, and the diagnosis was made beginning from this pivotal finding.

Ehlers-Danlos Syndrome with Recurrent Spontaneous Pneumothoraces and Cavitary Lesion on Chest X-ray as the Initial Complications

“…The reason for the initial manifestations in the present case being limited to the lung is unclear. Although there was a report suggesting a relation between the location of the gene mutation and its phenotype (11), the location of the mutation in the present case (P.Gly 603 Asp) was remote from that in the previous report (11), and further studies are needed to clarify this matter.…”

“…Lungs of vEDS patients are vulnerable to lacerate, which is suggested to manifest initially as acute hematoma, followed by organizing to organized hematoma. We speculate that when blood is absorbed or excreted through the airways, a cavity is then formed, and this might result in the creation of a fibrous nodule, as reported previously (7)(8)(9)(10)(11). Fragility of the pleural tissue may cause the formation of blebs, the rupture of which may lead to pneumothoraces.…”

“…Initial complications stemming from other organs were seen in only 5% of cases. To our knowledge, only 2 cases of patients developing pulmonary symptoms as an initial manifestation have been reported (11,12). In the present case, the initial complication was spontaneous pneumothorax, and vascular complications occurred 7 years after the initial pulmonary complication.…”

Pathology of the large intestine in patients with vascular type Ehlers-Danlos syndrome

“…The same mutation was identified in the 42-year-old patient presented in this study. The mutation is located in the α-helix of procollagen 3a; mutations in this area are frequently found in patients with Ehlers-Danlos syndrome type IV [11,18,24]. Patient 2 One month after his mother (patient 1) died, her 21-year-old son presented with acute abdomen.…”

Genetic Aspects of the Vascular Type of Ehlers-Danlos Syndrome (vEDS, EDSIV) in Japan

“…The COL3A1 mutation identification method we described previously 4,5 was further modified to amplify 1 COL3A1 cDNA fragment. Total cellular RNA and genomic DNA were extracted from cultured dermal fibroblasts and complementary DNA was synthesized by priming with random hexamers as described previously.…”