Congenital Fiber-Type Size Disproportion
Congenital fiber-type size disproportion represents a heterogenous group of conditions most likely with varied genetic defects. The condition was initially delineated by Brooke (73) on the basis of the muscle biopsy picture demonstrating type I fibers that are smaller than type II fibers by a margin of more than 12% of the diameter of the type II fibers.
The mean reduction in fiber diameter is 41% and ranges up to 78%. A number of disorders, such as congenital myopathies (nemaline rod, centronuclear, and multi-minicore), Emery-Dreifuss MD and myotonic dystrophy 1, rigid spine syndromes, congenital muscular dystrophy (SEPN1), LGMD 2A, and severe spinal muscular atrophy, all may show small type I fibers and should be excluded. The diagnosis of congenital fiber-type disproportion should be made only in the presence of normal-sized or enlarged type II fibers and not in cases where both type I and type II fibers are small. Serum CK has been normal to times the upper limit of normal.Patients typically present with infantile hypotonia and delay in gross motor milestones. The severity has been noted to be quite variable, but it is generally nonprogressive or improves with time. Limb weakness of variable severity may be diffuse or affect proximal muscles. Deep tendon reflexes are reduced. Ophthalmoplegia, facial weakness, and bulbar weakness are rare findings but associated with more severe cases. Intelligence is normal. There is generally short stature and low weight. Patients may exhibit a long, narrow face; high-arched palate; and deformities of the feet, including either flat feet or occasionally high- arched feet. Kyphoscoliosis has been reported. Lenard and Goebel (74) documented a case with fairly severe weakness and associated respiratory deficit, necessitating tracheostomy. The author has managed two cases (a mother and son with presumed autosomal-dominant inheritance), who both developed nocturnal hypoventilation requiring bilevel positive airway pressure.
Patients with muscle biopsies indicative of congenital fiber-type disproportion and ptosis should be evaluated for a congenital myasthenic syndrome, as the author has seen a number of cases in recent years of congenital structural neuromuscular junction disorders that have associated nonspecific changes on muscle biopsy, interpreted to be congenital fibertype disproportion. This is an important distinction, as some of these patients with congenital myasthenia respond to pharmacologic intervention.
The mode of inheritance for congenital fiber-type disproportion is varied, with both autosomal-recessive and autosomal-dominant patterns of inheritance reported.