A 19-year-old female patient presented with a 4-year history of pain in multiple joints. Ibuprofen and heating pads provided mild relief, but her symptoms were recurring. She also reported having overly flexible joints, daily musculoskeletal pain, repeated joint dislocations, hearing loss in her left ear, and easy bruising. She did not report any other symptoms. The joint pain was not related to injury, and she had never participated in organized sports. Her medical history included a meniscal tear without inciting trauma. The patient’s mother and maternal uncle also had joint hyperlaxity.

Physical examination revealed soft, nonpigmented papules on the lateral aspect of the heels (Figure 1). The patient also had hyperlaxity in the first and fifth digits (Figure 2), elbows, and knees. No joint swelling or tenderness was noted. Physical and cardiovascular examination findings were otherwise unremarkable.

QUESTION

Based on the patient’s history and physical examination, which one of the following is the most likely diagnosis?

• A. Cutis laxa.

• B. Ehlers-Danlos syndrome.

• C. Larsen syndrome.

• D. Marfan syndrome.

• E. Osteogenesis imperfecta.

DISCUSSION

The answer is B: Ehlers-Danlos syndrome. This is a group of inherited connective tissue disorders that cause hyperextensibility and tissue fragility in the skin, joints, vasculature, and various internal organs. Ehlers-Danlos syndrome affects 1 per 5,000 people and often presents with joint hyperlaxity, although it can manifest with a variety of pathologies.¹ The patient’s history of joint hyperlaxity, recurrent atraumatic injuries, and hearing loss are consistent with this condition. The physical examination findings and family history are especially consistent with Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome can occur as a spontaneous genetic mutation or be inherited in an autosomal dominant or recessive pattern. Genetic counseling and testing are required for diagnosis of specific subtypes. The 13 clinical subtypes have different presentations and genetic etiologies. Management of the condition is symptomatic because no cure is available. Patient education regarding lifestyle changes and prospective care can help to decrease the occurrence of joint dislocations.²

Cutis laxa is an inherited connective tissue disorder characterized by loose or redundant skin with loss of elasticity and premature aging. The skin is slow to reform from distention. Patients present with hyperlaxity of the skin but generally do not have joint issues. The only treatment is plastic surgery for cosmesis.³

Larsen syndrome is a rare genetic disorder of connective tissue. It is caused by mutations in the cytoskeletal protein filamin B. Symptoms can include dislocations in large joints, a round face, saddle nose, short stature, clubfoot, cleft palate, widely spaced eyes, and spinal anomalies.⁴

Patients with Marfan syndrome can have joint hyperlaxity and other findings similar to those of Ehlers-Danlos syndrome. However, Marfan syndrome features key physical findings such as ectopia lentis, pectus carinatum, long limbs, kyphosis, scoliosis, hindfoot valgus, and characteristic facial features such as crowded oral maxilla and high-arching palate. Additionally, patients with Marfan syndrome typically have aortic pathology.⁵

Osteogenesis imperfecta can present with hearing loss, blue sclera, and joint and skin hyperlaxity. The classic symptoms include recurrent fractures, bone deformities, and short stature. The prevalence of osteogenesis imperfecta is an estimated 1 per 15,000 people, and cases vary in severity. The most common treatment is bisphosphonates to reduce fracture rates and bone pain.⁶