Multiple congenital skull fractures as a presentation of Ehlers-Danlos syndrome type VIIC.

We describe a newborn infant with multiple congenital skull fractures and intracranial hemorrhage. He also had multiple skin folds suggesting a connective tissue abnormality. Electron microscopy of the skin biopsy showed collagen abnormalities with a "hieroglyphic appearance." The analysis of the synthesis of collagen in the cultured dermal fibroblasts demonstrated an accumulation of procollagen I. Molecular analysis found a nonsense mutation Q225X in ADAMTS2 gene, which encodes procollagen I N-terminal proteinase. All these findings confirmed the diagnosis of Ehlers-Danlos syndrome type VIIC (MIM 225410). Family studies suggested a founder effect in Ashkenazi Jews originating from Belarus. Prenatal diagnosis in the subsequent pregnancy reassured the parents that the fetus was an unaffected carrier.

A four-generation Ehlers-Danlos syndrome with vascular dissections. Skin ultrastructure and biomechanical properties.

Ehlers-Danlos syndrome (EDS) is heterogenous with regard to genetic traits, clinical manifestation, the biomechanical and microscopic properties of connective tissues, and basic molecular defects. We report on nine relatives of four generations who suffered from large vessel dissections and cutaneous microscopic changes consistent with EDS. Measurements of the mechanical properties of skin were performed using a computerized suction device (Cutometer). Morphological and biomechanical alterations suggestive of EDS were present in all examined subjects. A loose network of collagen bundles was admixed with clumsy elastic fibres. Factor XIIIa-positive dermal dendrocytes looked almost normal but were slim and rarefied in four subjects. The severity in ultrastructural alterations of the collagen network differed among the subjects. The group with the most prominent changes showed the most striking biomechanical alterations characterized by increased biologic elasticity without any excess in skin extensibility. A positive correlation was found between skin extensibility and elasticity. In conclusion, distinct alterations in the collagen scaffolding were found to be correlated to variable severity in biomechanical alterations of the skin. The predictive value of these changes for large vessel dissections in some families at risk remains to be settled.

Collagen fibril arabesques in connective tissue disorders.

BACKGROUND: In various connective tissue disorders, collagen fibrils and elastic fibers may exhibit some ultrastructural abnormalities. OBJECTIVE: This electron microscopy study focused on collagen fibril orientation and unusual shapes in the dermis of Ehlers-Danlos syndrome (EDS) and related entities, including spontaneous cervical artery dissection syndrome and recurrent preterm premature rupture of fetal membranes syndrome. RESULTS: In addition to some abnormal fibril shapes typically found in these syndromes, other conformations (hook shaped, S shaped, ring shaped) that have not been illustrated previously in the literature were observed. CONCLUSION: The abnormal collagen fibril conformations observed in EDS and other related conditions characterized by tissue fragility likely affect both the internal cohesiveness of the bundles and the mechanobiologic properties of the tissue.

Ehlers-Danlos-like dermal abnormalities in women with recurrent preterm premature rupture of fetal membranes.

Preterm premature rupture of membranes (PPROM) likely results from weakening of the constituent connective tissue. It is uncertain if the alterations are limited to the fetal membranes or are also present in other sites such as the skin. The aim of the study was to compare the dermal structure of women suffering from recurrent PPROM with the dermis of both non-pregnant women and women with uneventful gestation. Skin biopsies were taken from 42 women who recently underwent PPROM, 33 women with uneventful gestation and 33 non-pregnant women. Histochemistry, immunohistochemistry, and electron microscopy were performed on these specimens and analyzed blindly. Morphologic changes were found in the dermis of most (33 of 42 at optical microscopy and 40 of 42 at ultrastructure) of the women suffering from PPROM. They were reminiscent of those found in some types of Ehlers-Danlos Syndrome (EDS). However, there was no clinical evidence suggesting a recognized form of EDS. We conclude that some cases of PPROM are a systemic connective tissue disorder representing a yet unidentified type of EDS.

Ehlers-Danlos-like syndrome in 2 dogs: clinical, histologic, and ultrastructural findings.

BACKGROUND: Ehlers-Danlos syndrome comprises a group of rare inherited connective tissue diseases characterized by skin hyperextensibility, joint laxity, skin and vessel fragility, and poor wound healing. OBJECTIVE: The purpose of this report was to describe the clinical, histologic, and ultrastructural findings in 2 dogs with collagenopathies consistent with Ehlers-Danlos syndrome. METHODS: Two dogs were examined clinically; skin extensibility index was calculated. Skin biopsies obtained from the dorsum were examined by light and electron microscopy. RESULTS: Both dogs had clinical signs of skin hyperextensibility and fragility, lower skin elasticity, vessel fragility, and poor wound healing. One dog had a hip dislocation, and the other had bilateral medial patellar luxation (grade II), subcutaneous hematomas produced by minimal trauma, and generalized periodontitis. Histologic and ultrastructural examination confirmed abnormalities in the structure and arrangement of collagen fibrils. Fibroblasts were characterized by variable dilatation of the rough endoplasmic reticulum, and anomalous elastic fibers (elaunin fibers) were present in the dermis. CONCLUSION: Although the primary defects underlying collagenopathies in animals are still unknown, analysis of the ultrastructural changes in collagen fibrils and clinical findings could facilitate better characterization of these disorders in dogs.