EDS Hypermobility Study of 21 Patients
A very detailed study of 21 patients with Ehlers-Danlos Syndrome. This is a 9 part series by experts in the field of EDS research.
Castori M, Camerota F, Celletti C, Danese C, Santilli V, SaraceniVM, Grammatico P. 2010.
Natural history and manifestations of the hypermobility type Ehlers
–Danlos syndrome:A pilot study on 21 patients. Am J Med Genet Part A 152A:556–564.
Hypermobility type Ehlers–Danlos syndrome (HT-EDS) is a relatively frequent, although commonly misdiagnosed variant of Ehlers–Danlos syndrome, mainly characterized by marked joint instability and mild cutaneous involvement. Chronic pain, asthenia, and gastrointestinal and pelvic dysfunction are characteristic additional manifestations. We report on 21 HT-EDS patients selected from a group of 40 subjects with suspected mild hereditary connective tissue disorder. General, mucocutaneous, musculoskeletal, cardiovascular, neurologic, gastrointestinal, urogynecological, and ear–nose–throat abnormalities are investigated systematically and tabulated. Six distinct clinical presentations of HT-EDS are outlined, whose tabulation is a mnemonic for the practicing clinical geneticist in an attempt to diagnose this condition accurately. With detailed clinical records and phenotype comparison among patients of differentages, the natural history of the disorder is defined. Three phases (namely, hypermobility, pain, and stiffness) are delineated based on distinguishing manifestations. A constellation of additional, apparently uncommon abnormalities is also identified, including dolichocolon, dysphonia, and Arnold–Chiari type I malformation. Their further investigation may contribute to an understanding of the pathogenesis of the protean manifestations of HT-EDS, and amore effective approach to the evaluation and management of affected individuals.
Ehlers–Danlos syndrome (EDS) comprises a clinically variable and genetically heterogeneous group of inherited connective tissue disorders mainly characterized by skin hyperextensibility, joint hypermobility, and vascular and internal organ fragility [Callewaert et al., 2008]. The overall incidence of this condition has been estimated at approximately 1:5000 [Steinmann et al., 2002]. According to the most recent classification, six major forms exist, while other variants are considered rare [Beighton et al., 1998]. The clinical variability of each EDS subtype is extremely wide and the diagnosis is not always straightforward even for the experienced clinician. Misdiagnosis or lack of diagnosis represents a major burden for patients with EDS. In fact, a recent survey by the European Organization for Rare Diseases (EURORDIS) has demonstrated that among patients belonging to 16 major rare diseases, those affected with EDS have the longest delay in diagnosis and request consultation of up to 20 specialists before obtaining the correct diagnosis [Kole and Faurisson, 2009]. This has severe consequences on the quality of life of the patients [Castori et al., 2009], usually in term of excessive financial and time expense, superfluous investigations, wrong therapies, delay of appropriate treatments, and preventable worsening of the disease state. Among the different forms of EDS, the hypermobility type (HTEDS) is the most difficult to diagnose. This condition is an autosomal dominant trait and is more common in females. The HT -EDS represents a clinical continuum with the so-called (benign) joint hypermobility syndrome (JHS) [Grahame, 1999; Tinkle et al., 2009]. There is also a signi ficant overlap with other forms of EDS, Stickler syndrome, osteogenesis imperfecta, and various fibrillinopathies [Grahame, 2000]. Given the lack of any skin, skeletal, ocular, or internal organ key anomaly, the phenotype of HT-EDS is limited to ligamentous laxity and minor and unspecific cutaneous defects [Hakim and Grahame, 2003]. Although recent papers pointed out an unexpected broadening of the phenotype [Hakimand Grahame, 2003], very little attention has been paid in the clinical genetics literature for the elaboration of evaluation strategies for proper diagnosing and counseling these patients. Here, we report our experience on 21 patients with HT-EDS. Accurate phenotype study allowed us to further delineate the natural history and the clinical complexity of this condition.
We do not have room on our site for this detailed report.