Ullrich congenital muscular dystrophy.
Incidence
CMD are autosomal recessive diseases affecting both sexes equally, but in this condition, dominant mutations contribute to nearly 50% of cases. Although precise epidemiological data are not available, this is one of the common variants of congenital muscular dystrophy.
Clinical Characteristics
This is one of the most common forms of congenital muscular dystrophy. Typical features of an Ullrich congenital muscular dystrophy patient are presentation in the neonatal period with hypotonia and kyphosis of the spine, frequently combined with proximal joint contractures, torticollis, and hip dislocation. The distal joints show hyperlaxity with extended talipes and protruding calcaneus. Contractures tend to get worse and eventually affect also the previously lax ankles, wrists, and fingers. Maximum motor function is variable: some children never walk whereas others achieve ambulation in time or with delay. Progressive functional difficulties, mostly secondary to increased contractures leading to loss of ambulation after a period of independence, are common. The skin typically shows follicular hyperkeratosis. Ventilatory insufficiency almost invariably develops in the first or second decade. In summary, typical features include presentation in the neonatal period with hypotonia, kyphosis of the spine, proximal-joint contractures, torticollis, and hip dislocation. Combined with the above is distal-joint hyperlaxity with a protruding calcaneus. Patients with severe cases may lack hyperlaxity. Kyphosis and proximal contractures may improve with therapy, but contractures recur and eventually involve previously lax distal joints. Some patients never walk, whereas others walk in time or with delay. However, progressive disability, usually due to contractures, leads to loss of ambulation after 2-10 years. Respiratory insufficiency invariably develops in the first or second decade. Facial dysmorphism includes micrognathia, a round face with drooping of the lower lid, and prominent ears. Skin changes typically include follicular hyperkeratosis. Intelligence and brain MRIs are normal. Cardiac function is normal. The condition is due mutations in 1 of the 3 collagen VI chain genes, dominant mutations contribute to nearly 50% of cases. The genes responsible for this form are COL6A1 and COL6A2 on chromosome 21q22.3 and COL6A3 on chromosome 2q37. This condition is due to defects of proteins of the extracellular matrix of peripheral membrane proteins.
Precipitants
No anesthesia problems. There is no report of malignant hyperthermia in patients with Ullrich congenital muscular dystrophy.
Provocation Tests
None
Diagnostic Procedures
Serum CK levels are typically normal or slightly elevated. The necessary test to arrive to a final diagnosis is a muscle biopsy for collagen VI immunostaining. This is usually abnormal in Ullrich congenital muscular dystrophy, however, the changes in some patients with COL6A genes mutations can be subtle and limited to the basal lamina. Patients with completely absent protein tend to be more severely affected. The identification of the causative mutation in one of the collagen 6 genes will eventually confirm the diagnosis at the molecular level.