Bethlem Myopathy

Bethlem myopathy is a mild, slowly progressive collagen VI-related muscular dystrophy (COL6A1, COL6A2, COL6A3), usually autosomal dominant. It is at the milder end of the collagen VI spectrum with Ullrich congenital muscular dystrophy.

Pathophysiology. Variants impair the assembly or secretion of collagen VI microfibrils in the extracellular matrix, weakening muscle fibre attachment.

Onset is in infancy to adulthood with proximal limb weakness (more in the legs), distal joint hyperlaxity, with contractures of the fingers (flexion), elbows, ankles and neck (rigid spine), keloid scarring, follicular hyperkeratosis and soft palmar skin. Respiratory weakness affects a minority. Some patients lose walking after age 50. Cardiac involvement is absent.

Creatine kinase is normal or mildly raised. Muscle MRI shows rim sign (peripheral fatty change in the vastus lateralis) and central shadow in rectus femoris. Muscle biopsy or skin fibroblast studies show reduced collagen VI. Genetic testing of COL6A1, COL6A2 and COL6A3 confirms the diagnosis. Check pulmonary function.

Differential diagnosis.

• Emery-Dreifuss muscular dystrophy, limb girdle muscular dystrophy and Pompe disease.
• Ullrich congenital muscular dystrophy, rigid spine syndrome and myofibrillar myopathy.

Contractures. Regular stretching, physiotherapy, night splints and surgical release for severe contractures.

Respiratory. Monitor forced vital capacity yearly, and offer nocturnal ventilation for hypoventilation.

Skin. Avoid unnecessary surgery over keloid prone areas, and counsel about scarring.

Mobility. Orthoses, walking aids and falls prevention.

Cardiac. Baseline ECG and echocardiography.

Genetic counselling. Offer to family members.

Monitoring. Strength, joints and respiratory function yearly.

Referral and escalation. Refer to neuromuscular services and genetics.

Special groups. In pregnancy, monitor respiratory function.