A 12-year-old boy presents to his pediatrician with pain in his knees while walking. On physical examination, he is noted to be short, has hyperextensibility of the skin, and hypermobile joints (Figures 224-1 and 224-2). His mother mentions that there are family members who have hypermobile joints, and who have had problems with dislocation and sprains of their joints. The pediatrician makes a clinical diagnosis of Ehlers-Danlos Syndrome and orders an echocardiogram, which is normal.
The Ehlers–Danlos syndromes (EDS) constitute a genetically heterogeneous group of conditions, characterized by fragility of the connective tissues, resulting in skin, ligament, joint, blood vessels, and visceral organ manifestations. The clinical spectrum ranges from mild skin and joint hyperlaxity to severe physical disability and life-threatening vascular complications.
The prevalence of EDS (all types) is estimated to be approximately one in 5,000 individuals.1
The most recent classification of EDS relies on clinical and biochemical criteria.2
Classification of the EDS types and prevalence:
Classic type—Affects 1 in 20,000 to 40,000 individuals.
Hypermobility type—Affects 1 in 10,000 to 15,000 individuals.
Vascular type—Affects 1 in 250,000 individuals. Accounts for about 5 percent of cases of EDS. Not often diagnosed until adulthood.
Kyphoscoliosis type—Very rare.
Arthrochalasia type—Very rare.
Dermatosparaxis type—Very rare
The vascular form of EDS is the most dangerous, because it is associated with spontaneous rupture of medium and large-sized arteries and hollow organs, especially the large intestine and uterus; vascular events typically occur between the third and fifth decade.
Etiology and Pathophysiology
Mode of inheritance is autosomal dominant for all forms of EDS except the kyphoscoliosis and dermatosparaxis types (recessive mode), and an unclassified X-linked form which is extremely rare.
Abnormalities of mature collagen structure in extracellular matrices of multiple tissues (skin, tendons, blood vessels, and viscera) are common to all forms of EDS.
Classic EDS is associated with defects in type V collagen, corresponding to mutations of COL5A genes, as well as type I collagen (COL1A1).
The precise etiology for the hypermobility form has not been identified.
Vascular EDS involves a deficiency in type III collagen and several studies suggest that mutations of gene COL3A1 lead to this deficiency.3
The kyphoscoliotic type of EDS is caused by a deficiency of lysyl hydroxylase (PLOD), a collagen modifying illness.
The arthrochalasia form of EDS results from a defect in type I collagen, caused by mutations in the COL1A2 genes.
The diagnosis of EDS is based solely on clinical criteria, which have been established for the six major types of EDS.
Major and minor criteria have been established for each type; the presence of one or more major criteria is highly indicative and warrants laboratory confirmation if possible.
A minor criterion is less specific, but the presence of one or more minor criteria contributes to the diagnosis of a specific type; in the absence of a major criterion, minor criteria are not sufficient to establish a diagnosis.
Positive family history is a minor criterion for all forms.
Skin hyperextensibility (Figure 224-1) should be tested at a site not subjected to mechanical forces or scarring, and measured by pulling up the skin until resistance is felt.
Joint hypermobility should be assessed using the Beighton scale. A score of 5 or greater defines hypermobility:
Passive dorsiflexion of the fifth finger >90° (one point if present, 2 points if bilateral).
Passive flexion of thumb to the forearm (one point if present, 2 points if bilateral).
Hyperextension of the elbow beyond 10° (one point if present, 2 points if bilateral).
Hyperextension of the knee beyond 10° (one point if present, 2 points if bilateral).
Ability to place the palms on the floor with extension of the knees (one point if present).
Easy bruising is defined as spontaneous ecchymosis, frequently located in the same areas, and causing a brownish discoloration.