Academic journal article Genetic Counseling

Long Term Follow Up of a Woman with Classic Form of Ehlers-Danlos Syndrome Associated with Rare Manifestations and Review of the Literature

Academic journal article Genetic Counseling

Long Term Follow Up of a Woman with Classic Form of Ehlers-Danlos Syndrome Associated with Rare Manifestations and Review of the Literature

Article excerpt

Summary: Long term follow up of a woman with classic form of Ehlers-Danlos syndrome associated with rare manifestations and review of the literature: We present the case of a 46 year-old woman with the classic type of Ehlers-Danlos syndrome who developed the rare manifestations of colon diverticula and mitral valve prolapse. We emphasize on clinical features and complications associated to this type of the syndrome, which gradually developed in our patient. A review of the literature referring to the epidemiology, molecular basis and manifestations of the classic type Ehlers-Danlos syndrome is also discussed.

Keywords: Classic EDS - Classification - Collagen - Colon diverticula - Mitral valve prolapsed.


Ehlers-Danlos Syndrome comprises a clinically and genetically heterogeneous group of inheritable connective tissue disorders. The essential defect is attributed to deficient collagen synthesis and metabolism. It is characterized by joint hypermobility, skin hyperelasticity and tissue fragility affecting skin and vessels (6, 7, 19). It is one of the oldest known causes of bruising and bleeding and was first described by Hippocrates in 400BC. It was not earlier than 1901 when a Danish dermatologist, Edvard Ehlers, recognized the condition as a distinct entity, and 1908 when a French dermatologist, named Henri-Alexander Danlos, who suggested skin extensibility and fragility as the cardinal features of the syndrome (6, 17). Since then, ten or even more types have been described according to the clinical presentation, biochemical and molecular findings, with major and minor diagnostic criteria established for each type (16). The prevalence of EDS in the general population is ranging from 1:5000 births to 1:10.000 births without racial predilection (1, 7, 14, 17, 22). Classic Ehlers Danlos is the most frequent type and its incidence counts 1:20.000-1:40.000 in the general population with main clinical characteristics joint laxity, hyperextensibility of skin and poor wound healing (22) (Table I).

Molecular basis of classic type EDS has been partly identified. The three fundamental mechanisms of the disease include deficiencies of collagen-processing enzymes, dominant-negative effects of mutant collagen a-chains and haploinsufficiency (1). Haploinsufficiency of COL5A1 appears to be frequently at fault, though splice site mutations leading to exon-skipping, few missense mutations causing glycine substitution in either COL5A1, COL5A2 and a splice-acceptor mutation with a complex outcome, located on the N-propeptide-encoding region of COL5A1 have also been reported (1, 12, 18). Furthermore, complete absence of tenascin X, a non-collagenous protein caused by mutation on TNXB gene, leads to an autosomal recessive condition with similarities to classic EDS but without atrophic scars strengthening further the heterogeneity hypothesis (7, 10, 12, 13, 18). Thus, not all classic EDS pedigrees are linked to COLA5A1, COL5A2; only in one third of patients with classical EDS the disease is caused by a mutation leading to a non-functional COL5A1 allele, resulting in diminished amount of type V collagen while in a smaller proportion of patients, mutation of COL5A1 or COL5A2 genes cause a structurally altered and functionally defective collagen V protein (7, 12, 13, 18). No distinct genotypephenotype correlation has emerged (12).

We report on a patient with classic Ehlers-Danlos who developed colon diverticula, an unusual complication of EDS of this type.


Our female patient is the first child of non consanguineous and phenotypically normal parents with no family history of genetic disorders. She was born after a 38 weeks uncomplicated pregnancy with a normal delivery and birth weight of 3100 g, length of 49 cm and head circumference of 34 cm (all measurements were within 50th percentile) while her perinatal period was free of complications. In early childhood she developed fragile skin, post-traumatic ecchymoses, bruises and "cigarette paper-like" scars. …

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