INTRODUCTION

Congenital myopathies include many genetically distinct diseases which have in common the early appearance of symptoms and characteristic morphological findings.

AIM

To resume clinical, pathological and genetic findings of the most frequent myopathies in this group.

DEVELOPMENT

The most severe of these group is myotubular myopathy; affected boys die frequently in the neonatal period due to respiratory failure. The altered protein, myotubularin, is involved in the metabolism of PI3P. The gene mutated is in Xq28 and more than 140 different mutations have been reported. Centronuclear myopathy is a genetically heterogeneous group, most frequently recessive but sometimes dominant and with a variable clinical course; childhood and adolescent cases usually present facial weakness and ophthalmoplegia together with proximal weakness, while adult forms show symptoms similar to limb girdle dystrophies. The protein responsible of the disease as well as the genetic locus involved are still unknown. Central core disease (CCD) is a scarcely progressive disease frequently associated with skeletal malformations. The inheritance is usually dominant. CCD has an important association with malignant hyperthermia and both diseases share the same gene in 19q13, locus of the RYR1 gene which encodes the ryanodine receptor. Minicore myopathy is a recessive disorder which shows four different phenotypes, the most frequent being the 'classical' one, with axial weakness, scoliosis and severe respiratory insufficiency; some of these cases have mutations in the selenoprotein N gene. Other phenotype with slowly progressive weakness and hand atrophy has a homozygous mutation in the RYR1 gene. Nemaline myopathy shows four different clinical and genetic types according to the age of beginning of symptoms and the type of inheritance. Several different genes have been identified: TPM3 in 1q21, NEB in 2q21 22, ACTA1, TPM2 and TNNT1.