Bethlem Myopathy

Genetic disorder consisting of a benign congenital myopathy and contractures.

Benign Congenital Muscular Dystrophy.

Unknown. Since the original report of the condition in 1977 by J. Bethlem and G.K. Van Wijngaarden, the myopathy has been described in at least nine pedigrees from various geographical locations, including the Netherlands, Poland, and Canada. The largest pedigree with the disorder was of French-Canadian ancestry in which the disease was traced back through seven generations.

Autosomal dominant. Gene map locus is most often 21q22.3, but in some patients is 2q37, suggesting a locus heterogeneity within Bethlem myopathy.

Genetic linkage studies suggest Bethlem myopathy is caused by mutations in the genes encoding the three constituent α-chain subunits of type VI collagen. Microfibrillar type VI collagen is believed to play a role in bridging cells with the extracellular matrix.

Made by clinical features consistent with the condition. Electromyography demonstrates a myopathic pattern. Muscle biopsy reveals nonspecific features of a myopathy. Nerve conduction is normal, and creatinine phosphokinase serum levels are normal or mildly elevated.

Characterized by a benign limb girdle myopathy with mild-to-moderate weakness and wasting of muscles. Onset is in early infancy or childhood (age 2-5 years) with a benign course and slow progression, leaving some of the affected patients only minimally impaired in old age. However, many patients require a wheelchair after 50 years of age, and some die of respiratory failure as a consequence of progressive respiratory muscle weakness, particularly of the diaphragm. Proximal and extensor muscles are more affected than distal and flexor muscles. Early flexion contractures involve the elbows, ankles, interphalangeal joints of the last four fingers, and planta pedis. Congenital torticollis may be present. Cardiac and respiratory involvement usually is not a feature of this condition.

Detailed clinical history and examination are required to determine the exact nature of the myopathy and the progression of the condition. Evaluate the severity of any flexion deformities and congenital torticollis. Obtain family history of previous anesthetic complications (hyperthermic response). Blood work should include creatinine phosphokinase and electrolytes.

Airway management, including direct laryngoscopy and tracheal intubation, may be difficult in the presence of fixed flexion deformities of neck muscles or congenital torticollis (awake fiberoptic intubation or inhalational induction in children followed by fiberoptic intubation may be required). Positioning and venous access may be difficult because of flexion deformities. Although congenital myopathies have been associated with malignant hyperthermia, the evidence supporting this causal relationship is poor. No case reports of malignant hyperthermia reaction in Bethlem myopathy have been published. Nevertheless, caution should be exercised when using known trigger agents, and full monitoring (including core and peripheral temperature) should be used in the perioperative period. Depending on the degree of muscle weakness and the procedure, postoperative mechanical ventilation may be required.

Avoidance of known trigger agents may be advisable until more information about the condition is available. Nondepolarizing muscle relaxants, if used, should be titrated to effect using a peripheral nerve stimulator. The benign myopathy associated with this condition, which makes it unique among the other congenital myopathies, suggests an exaggerated response to these agents is unlikely. Due to the risk of a hyperkalemic response, succinylcholine should not be used in patients with significant muscle weakness. Anticholinergic premedication is recommended if fiberoptic intubation is planned.

Ullrich Disease: An autosomal recessive disorder characterized by muscular weakness and orthopedic findings. Abnormal cellular immunity may be present.

Limb-Girdle Type of Muscular Dystrophy (LGMD): This is an inherited symmetric muscular weakness, initially of the lower limbs, with slow progression and associated cardiac anomalies.

Emery-Dreifuss Muscular Dystrophy (EDMD): X-linked form of muscular dystrophy with an onset at approximately 5 years of age and includes cardiac anomalies.

Hauptmann-Tannhauser Muscular Dystrophy: Symptoms are similar to Emery-Dreifuss muscular dystrophy, but inheritance is autosomal dominant instead of X-linked.