A 7-year-old White boy was referred because of an elevated serum creatine kinase (CK). For 6 months he had experienced swelling of the right thumb and later of the first metacarpal phalangeal and interphalangeal joints of both hands. The diagnosis of juvenile rheumatoid arthritis (JRA) was tentatively made, and he was treated with nonsteroidal antiinflammatory drugs with marked improvement. His parents also noted “large muscles” since his early childhood, and his pediatrician found elevated serum enzymes with an alanine transaminase of 237 IU/L (normal, <45 IU/L) and aspartate transaminase of 187 U/L (normal, <36 IU/L). l -Lactate dehydrogenase was 1941 IU/L (normal, 110–220 IU/L) and CK of 8724 IU/L (normal, <200 IU/L).
He was born to a 39-year-old gravida III, para II mother at term and from an uncomplicated pregnancy. Labor lasted 4 hours, and because of breech presentation, he was delivered by C-section. Birth weight was 6 lb, 7 oz. He cried immediately. There were no prenatal complications. He sat at 4 months, crawled at 9 months, pulled to standing at 10 months, and walked at 1 year of age. Speech development was thought to be normal. He was repeating the first grade but was doing fairly well in school. The mother reported that he often complained of his legs hurting. This was more severe over the past 2-month period, particularly after exercise. He had no significant weakness and kept up with other children.
Family history was negative. He had no siblings.
Past medical history was remarkable for hernia surgery at 2 years of age; otherwise, there had been no other hospitalizations or injuries. The review of systems was in all other aspects negative.
Physical examination showed an alert, cooperative young boy. Height was normal at 115.8 cm. There were no birthmarks. Cranial nerves were normal. Muscle strength testing showed no evidence of distal or proximal weakness. However, he had rather large calves, and the triceps, quadriceps, gastrocnemius, and abdominal wall muscles appeared hypertrophic ( Fig. 80-1 ), although the consistency of the muscle appeared normal. The heel cords were not tight. Finger-to-nose, heel-to-shin, and rapid alternating movements were well performed. He showed no Gowers maneuver when rising from the floor. Gait and stance were normal. There was no muscle tenderness or myotonia. The examination was otherwise unremarkable.
What is the Differential Diagnosis?
This patient presented initially with joint pains and was diagnosed with JRA; he also had muscle hypertrophy. The differential diagnosis of muscle hypertrophy includes myotonias, such as myotonia congenita and Schwartz–Jampel syndrome, but he had neither clinical myotonia nor dysmorphic features. Hypothyroidism could cause muscle hypertrophy and elevated CK, but there were no clinical features of this disease. Another consideration was Becker dystrophy, but the lack of weakness is somewhat against this diagnosis. Other dystrophies, such as limb-girdle muscular dystrophy (LGMD) and centronuclear myopathy, are considerations, as they could also cause muscle hypertrophy but mainly of the calf muscles. They all are associated with muscle weakness, but LGMD 2I, caused by mutations of the fukutin-related protein gene, is important in the differential diagnosis, because these patients manifest with not only muscle hypertrophy and weakness but also a cardiomyopathy similar to Becker dystrophy.
Metabolic myopathies should also be considered because of the exercise-induced muscle pains, but these do not cause muscle hypertrophy. He also had arthritis, which improved with nonsteroidal antiinflammatories; thus an associated myositis, causing muscle pain and swelling, should be included in the differential diagnosis, but the lack of weakness is also against this diagnosis.
Patients with spinal muscular atrophy rarely have large muscles, particularly in the calf, but the lack of weakness and the markedly elevated serum CK are against that diagnosis. Stiff-person syndrome and Isaacs syndrome cause muscle stiffness and large muscles, but these are unusual in children. Furthermore, the affected muscles are prominent mainly in the trunk, and these disorders do not cause such a high CK.
What Should Be Done Next?
Complete metabolic panel was normal, except for elevated alanine transaminase and aspartate transaminase. Thyroid-stimulating hormone, FANA, rheumatoid factor, and erythrocyte sedimentation rate were normal. Serum CK was high at 8300 IU/L (normal, <200 IU/L).
| Nerve and Site | Latency (ms) | Amplitude (mV) | Conduction Velocity (m/s) |
|---|---|---|---|
| Median Nerve R. | Normal ≤ 4.2 | Normal ≥ 6 | Normal ≥ 50 |
| Wrist | 3.6 | 10 | – |
| Elbow | 6.6 | 10 | 60 |
| Nerve | Latency (ms) | Normal Latency ≤ (ms) |
|---|---|---|
| Median nerve R. | 26.8 | 30 |
| Nerve | Onset Latency (ms) | Normal Onset Latency ≤ (ms) | Peak Latency (ms) | Normal Peak Latency ≤ (ms) | Amp (μV) | Normal Amp ≥ (μV) | Conduction Velocity (m/s) | Normal Conduction Velocity ≥ (m/s) |
|---|---|---|---|---|---|---|---|---|
| Median nerve R. | 2.3 | 2.6 | 2.8 | 3.1 | 36 | 20 | 57 | 50 |
| Muscle | Insrt Activity | Fibs | Pos Waves | Fasc | Amp | Dur | Poly | Pattern |
|---|---|---|---|---|---|---|---|---|
| Deltoid R. | Norm a | None | None | None | Dec | Brief | Many | Full b |
| Biceps brachii R. | Norm a | None | None | None | Dec | Brief | Many | Full b |
| First dorsal interosseous R. | Norm a | None | None | None | Norm | Norm | Few | Full |
a No myotonic discharges seen on EMG examination.
An EMG Test was Performed
What Were the EMG Findings?
The nerve conduction tests were normal. The needle test showed an absence of spontaneous activity, but many brief polyphasic motor unit potentials were seen during voluntary contractions. These findings were against the myotonias, other diseases of muscle irritability, or spinal muscular atrophy and indicate a primary myopathy.
What Should Be Done Next?
The next test done was DNA testing in lymphocytes using PCR multiplex for dystrophinopathy; it showed no evidence of DNA mutations. On follow-up, the patient’s arthritic symptoms disappeared.
What Should Be the Next Diagnostic Test?
A quadriceps muscle biopsy showed variation of fiber size, increased connective tissue, and frequent regenerating fibers with no evidence of necrosis. There was a patchy decreased staining for dystrophin ( Fig. 80-2 ) and (see Fig. 1.11 in Chapter 1) suggesting a dystrophinopathy like Becker dystrophy. This was confirmed by the Western blot test that showed dystrophin of normal size (about 400 kDa) but reduced in quantity to 20% of normal, confirming the diagnosis of a dystrophinopathy, such as Becker dystrophy.
