Clinical Summary

An 11-year-old male presents with a long-standing history of generalized muscle weakness and hyporeflexia. He was born at term following an uncomplicated pregnancy to a 28 year-old G1P0 mother in Korea; no perinatal feeding or respiratory difficulties were reported. Head lag was noted from birth. Since early childhood, he demonstrated poor strength and coordination, with current difficulties running, climbing, and inability to hop or ride a bicycle. Intellectual and social development are normal.  Parents are non-consanguineous and there is no family history of neuromuscular disease. His father has Behçet’s disease and a solitary functional kidney.

On physical examination, muscle bulk and strength are diffusely reduced. Manual muscle testing (MRC grading) reveals neck flexion 2/5, hip flexion 3/5, hip extension 3/5, and 4/5 strength in the remaining muscle groups. Facial weakness is mild and symmetric. Deep tendon reflexes are absent or markedly reduced (1+ triceps). Myotonia or contractures are absent. Generalized joint hypermobility is present. Cerebellar tests and gait are normal. Growth parameters are within normal limits (height and weight 80th percentile, head circumference 61st percentile).

Laboratory studies show a normal serum creatine kinase (84 U/L). Plasma lactate, amino acids, and urine organic acids are normal. Urinalysis demonstrates persistent microscopic hematuria. Electromyography and nerve conduction studies are normal.  The muscle ultrasound and skeletal muscle MRI suggest a mild to moderate non-dystrophic myopathic changes. Screening for myotonic dystrophy is negative (no DMPK or CNBP expansion). A mitochondrial panel (exome slice) is inconclusive. Muscle biopsy is pursued for further diagnostic evaluation.  

Discussion points

1. What are the major histological findings?
2. What is the differential diagnosis?
3. What ancillary testing would be most informative?
4. Are there clinical implications of the diagnosis?