Case 1, a 71-year-old retired Caucasian female rancher developed pain between her shoulders in her early 40s, which progressed to widespread body pain that she describes as feeling like a painful force field over her body, and is associated with fatigue. She was diagnosed with FM by her primary-care physician based on her symptoms, as well as chronic fatigue syndrome and irritable bowel syndrome. Medical history is notable for rheumatic fever in childhood, anxiety, hypercholesterolaemia, bilateral hand action tremor since the age of 65 years, peripheral neuropathy diagnosed at the age of 67 years, chronic cough, RP, osteoporosis and episodic vertigo. She takes three prescriptions and seven over-the-counter medications. Brain MRI shows mild non-specific white matter abnormality and mild volume loss. Her two FMR1
alleles have 30 and 106 CGG repeats with an activation ratio of 0.7. Her mRNA level is elevated at 3.12 (0.35). She meets diagnostic criteria for possible FXTAS [4
] and has two grandsons and a nephew with fragile X syndrome.
Case 2, a 60-year-old Caucasian woman was well until pain developed in her hands at the age of 50 years, which progressed to severe OA, requiring reconstruction of the base of her thumbs. Also, in her early 50s, she developed muscle aches and tenderness associated with poor sleep and severe fatigue; this was diagnosed as FM based on her symptoms, tender point examination and negative laboratory testing by her rheumatologist. The symptoms particularly flair up in the autumn and winter. In addition, she has been depressed and noticed impaired balance for 2 years. Medical history is remarkable for menopause at the age of 42 years, hypertension, hyperlipidaemia, osteopenia, temporal-mandibular disorder, rheumatic fever in childhood, gastric reflux, mitral valve regurgitation and supraventricular tachycardia. Brain MRI shows mild non-specific white matter abnormality. She has 35 and 73 CGG repeats with an activation ratio of 0.48 and mRNA is 1.93 (0.04). She does not have FXTAS, but has a family history of both fragile X syndrome and FXTAS.
Case 3 is a 49-year-old Caucasian female bookkeeper with gradual onset of muscle pain everywhere 3 years ago, which is now associated with severe fatigue. These worsened over the past 1.5 years, with symptoms being worst during autumn and winter. She was diagnosed with FM after an extensive negative laboratory evaluation. After an unsuccessful trial of duloxetine, she found relief with amitriptyline 20
mg at night and marked benefit from a yoga programme. Medical history is notable for menopause at the age of 39 years, depression, history of alcoholism with abstinence for 4 years, RP, vertigo, Bell's palsy, OA and scoliosis. She takes amitriptyline, vitamins and acetaminophen. Brain MRI shows mild non-specific white matter abnormality. She has 31 and 74 CGG repeats with an activation ratio of 0.64 and mRNA level of 1.35 (0.04). While she does not have FXTAS, her son has fragile X syndrome and her father had symptoms consistent with FXTAS.
Case 4, a 48-year-old retired Native American female human resource manager, had onset of muscle pain 5 years ago in her back, shoulders and arms. The pain worsened over the past 2 years and progressed to include her thighs and to be associated with severe fatigue. Medical history is significant for bilateral action hand tremor, neuropathy, SS/sicca syndrome (Ro negative), inflammatory polyarthropathy particularly involving her hands and feet, RP, irritable bowel syndrome, migraine, depression, panic attacks, cardiac arrhythmia, scoliosis and that she has had eight orthopaedic surgeries on her feet and knees. She takes 15 prescriptions, nine over the counter, and five as needed medications. Detailed immunological workup was negative. Brain MRI demonstrates mild left lateral ventricular enlargement, but no white matter disease. She has 20 and 108 CGG repeats with an activation ratio of 0.56 and mRNA level of 3.09 (0.41). She meets diagnostic criteria for possible FXTAS, and has two sons with fragile X syndrome.
Case 5, a 49-year-old Caucasian woman, has a 15-year history of FM, diagnosed by her rheumatologist, which began with pain in her back, arms and thighs and progressed to include her feet, chest and face. In recent years she developed chronic fatigue. She has a history of severe migraines, hypothyroidism, carpel tunnel surgery twice, intention tremor since the age of 47 years, ataxia with more than 10 falls over the past few years, vertigo episodes, bulimia and chronic depression. Her brain MRI shows mild atrophy and white matter disease in the frontal regions. She has 30 and 93 CGG repeats, an activation ratio of 0.15 and mRNA level of 3.71 (0.48). She meets diagnostic criteria for probable FXTAS, and has a son with fragile X syndrome. Also, her father died of FXTAS and sister with the premutation has FM and migraines.