The natural history, including orofacial features of three patients with Ehlers–Danlos syndrome, dermatosparaxis type (EDS type VIIC)

Abstract

Ehlers-Danlos syndrome (EDS) dermatosparaxis type (type VIIC) and the related disease of cattle dermatosparaxis, are recessively inherited connective tissue disorders, caused by a deficient activity of procollagen I N-proteinase, the enzyme that excises the N-terminal propeptide in procollagen type I, type II, and type III. Although well documented in cattle, to date only seven human cases have been recorded, most of them aged under 2 years. We document the natural history of three patients with EDS dermatosparaxis type, two of whom have been reported before the age of 2 years, and one new patient. The phenotype of the patients, and especially the facial resemblance, is striking, making this a clinically recognizable condition. The most consistent anomalies during the first years of life are premature rupture of the membranes, extreme skin fragility and easy bruising, large fontanels, blue sclerae, puffy eyelids, micrognathia, umbilical hernia, and short fingers. Joint hypermobility becomes more important with age. The children are at risk for rupture of internal organs due to soft tissue fragility, as is illustrated by different internal events in two of the three patients described here. Orofacial features include micrognathia, a frontal open bite, and gingival hyperplasia with varying degrees of hyperkeratosis. The deciduous dentition shows abnormal morphology of the molars, obliteration of the tooth pulp, and severe enamel attrition. The permanent dentition shows agenesis and microdontia of several teeth. Tooth discoloration, dysplastic roots, and tooth pulp obliteration are present in a restricted number of permanent teeth.

The RIN2 syndrome: a new autosomal recessive connective tissue disorder caused by deficiency of Ras and Rab interactor 2 (RIN2)

“…However, RIN2-deWcient patients have a later onset of their scoliosis and show no atrophic scarring of the skin nor ocular fragility. The facial characteristics of the RIN2-deWcient patients are to some extent reminiscent also of EDS dermatosparaxis type, but the more pronounced skin fragility and laxity, and extensive bruising, characteristic of dermatosparaxis, were not observed in these patients (Malfait et al 2004). Some phenotypic overlap also exists with GAPO syndrome (growth retardation, alopecia, pseudo-anodontia and optic atrophy), a rare autosomal recessive disorder of unknown cause (Goloni-Bertollo et al 2008), in which RIN2 was excluded as a causal gene by Basel-Vanagaité et al (2009).…”

The Ehlers-Danlos Syndrome

“…Other distinctive features are delayed closure of the fontanels, characteristic facies with edema of the eyelids and blue sclera, umbilical hernia and short stature. Fragility of internal tissues, with spontaneous bladder and diaphragmatic rupture, has been reported [ 47 ]. Whereas most of the initially reported patients showed a very severe phenotype, recognizable from birth, it is now clear that some patients present with a milder condition, which can delay the diagnosis.…”

Syndrome d’Ehlers-Danlos : à propos d’un cas

“…Les patients peuvent présenter des anomalies craniofaciales spécifiques dans le type dermatosparaxis ou un faciès marfanoïde dans les autres types [10]. La denture comporte quelquefois des anomalies de nombre [11], mais ce sont surtout les anomalies de forme qui prédominent [12] avec des sillons et des cuspides plus anfractueux, des racines souvent plus courtes, avec une dilacération plus ou moins marquée dont il faudra tenir compte lors des avulsions dentaires (Fig.…”