Congenital fiber type disproportion - 30 years on

Thirty years ago, M. H. Brooke coined the term "congenital fiber type disproportion" (CFTD) to describe 12 children who had clinical features of a congenital myopathy and relative type 1 fiber hypotrophy on muscle biopsy. It is now clear that this histological pattern can accompany a wide range of neurological disorders, leading to disillusionment with CFTD as a distinct nosological entity. To determine whether the CFTD has clinical utility as a diagnostic entity, we have reviewed the literature for cases of type 1 fiber hypotrophy and have used strict exclusion criteria to identify 67 cases of CFTD. Most patients presented at birth with weakness and hypotonia, had normal intelligence, and followed a static or improving clinical course. In 43% of families, more than 1 individual was affected. Failure to thrive was common and 25% of patients had contractures or spinal deformities. Bulbar weakness and ophthalmoplegia were less common and cardiac involvement was rare. Twenty-five percent followed a severe course and 10% had died at the time of reporting, all from respiratory failure. Ophthalmoplegia and facial and bulbar weakness were significantly associated with a poorer prognosis. The relatively homogeneous phenotype supports the retention of CFTD as a distinct diagnostic entity and familial occurrence suggests a genetic basis. Regarding the diagnosis of CFTD, we found no strong evidence that the minimum difference between type 1 and type 2 fiber sizes should be increased from 12% to 25%. We also list the other reported causes of relative type 1 fiber hypotrophy to aid their exclusion from CFTD.