Case 1. A 16-year-old girl visits her obstetrician for her first prenatal visit. Her genetic history questionnaire notes that her mother has chronic fatigue syndrome with arthritis, migraines, and irritable bowel syndrome. Her mother also has anxiety disorder and is viewed by the family as a hypochondriac. The obstetrician notes joint hypermobility and unusual skin elasticity on examination (Figure, A-C) and tells the girl that he would like her to see a cardiologist even though she has never had signs or symptoms of heart disease.
Figure: Digital extension (A) and joint hypermobility (B); skin elasticity (C) with “cigarette-paper”
Case 2. A 12-year-old girl is evaluated by an orthopedist because of frequent fractures and dislocations, particularly affecting her left knee that prevent her from participating on an elite soccer team. She was a “rubber-band” baby according to her mother, able to hold her bottle with her feet and often sitting in the “W” position. She required glasses for myopia at age 4 and will be starting orthodontic treatment for crowded teeth. She was delayed in her motor milestones and was very clumsy, with many falls when learning to walk. She can “pop” many of her joints and shows off by turning her elbows completely anterior and joining her hands, one over her shoulder, the other around her back. She has had 6 fractures of her wrists, elbows, and ankles, and frequently sprains her ankles.
Figure: (D) or keloid (E) scars; pectus and scoliosis due to skeletal flexibility and deformation (F)
Examination shows soft skin; a white scar with fine wrinkles over a site of fracture repair (Figure, D); and joint hypermobility, including the ability to bend her fingers back over 90 degrees and to touch her palms to the floor. She also had scoliosis of 8 degrees (Figure, F). X-rays films of her knees show lax ligaments and an area of dead bone on her lower left tibia; her hips show some joint erosion.
Case 3. A 2-year-old boy is evaluated by a pediatrician for motor delays because he is only now beginning to walk. He has a broad based and wobbly gait, prompting concern about a myopathy. Speech is normal. His physical examination seems otherwise normal except for many violaceous plaques over pressure points and some scars with purplish edges on his forehead, elbows, forearms, and knees (eg, Figure, E). His mother says he is very clumsy and falls frequently, and has required stitches on several occasions. She seems very intense and begins relating her own health problems, which have included disabling back and joint pain with need for vertebral fusion; dizziness on standing with occasional syncope, hypotension, and fatigue; abdominal pain with constipation or diarrhea (diagnosed as gastroparesis); frequent migraines that she attributes to poor circulation because she has Raynaud phenomenon and pooling with discoloration in her pelvic area; metrorrhagia with endometriosis that led to hysterectomy after her son’s birth. Prior physicians raised concern about maternal mental illness and child abuse, but this pediatrician ascertains that the boy was premature and diagnoses a familial illness.
To what common diagnosis do these disparate symptoms and findings point?
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7. Numbers following the disorder access the relevant entry in Online Mendelian Inheritance in Man. www.ncbi.nlm.nih.gov/omim. EDS type I classical (130000); EDS type II classical (130010); EDS type III hypermobility (130020) EDS type IV vascular (225400); EDS type VI ocular-scoliosis (229200); EDS type VIIA, B arthrochalasis (130060); EDS type VIIC dermatosparaxis (225410); EDS type VIII periodontal (130080).
8. Marfan syndrome (154700); homocystinuria (236300) osteogenesis imperfecta (166210); Beals contractural arachnodactyly (121050); Loeys-Dietz syndrome (609192); Pseudoxanthoma elasticum (264800) Stickler syndrome (108300); Larsen syndrome (150250).
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