Recessive myosin myopathy with external ophthalmoplegia associated with MYH2 mutations

Abstract

Myosin myopathies comprise a group of inherited diseases caused by mutations in myosin heavy chain (MyHC) genes. Homozygous or compound heterozygous truncating MYH2 mutations have been demonstrated to cause recessive myopathy with ophthalmoplegia, mild-to-moderate muscle weakness and complete lack of type 2A muscle fibers. In this study, we describe for the first time the clinical and morphological characteristics of recessive myosin IIa myopathy associated with MYH2 missense mutations. Seven patients of five different families with a myopathy characterized by ophthalmoplegia and mild-to-moderate muscle weakness were investigated. Muscle biopsy was performed to study morphological changes and MyHC isoform expression. Five of the patients were homozygous for MYH2 missense mutations, one patient was compound heterozygous for a missense and a nonsense mutation and one patient was homozygous for a frame-shift MYH2 mutation. Muscle biopsy demonstrated small or absent type 2A muscle fibers and reduced or absent expression of the corresponding MyHC IIa transcript and protein. We conclude that mild muscle weakness and ophthalmoplegia in combination with muscle biopsy demonstrating small or absent type 2A muscle fibers are the hallmark of recessive myopathy associated with MYH2 mutations.

A novel MYH2 mutation in family members presenting with congenital myopathy, ophthalmoplegia and facial weakness

“…The reason for a reduced number of histochemical type 2B fibers that express MyHC IIx is not evident but type 1 fiber predominance is common in many congenital myopathies. Unlike some previously reported recessive MyHC IIa myopathy cases we did not see any fat tissue proliferation in the biopsy material and MRI was not performed, but such fatty change is apparently affecting only some muscles [11,13].…”

“…Loss of histochemical type 2B fibers was also common with type 1 fiber uniformity [11][12][13]. In patients with missense mutations type 2A fibers could be present but they were smaller than normal [13]. Fatty infiltration was identified by muscle biopsy in several cases.…”

“…Muscle pathology showed absence of type 2A fibers in all cases with truncating mutations and most cases with missense mutations. Loss of histochemical type 2B fibers was also common with type 1 fiber uniformity [11][12][13]. In patients with missense mutations type 2A fibers could be present but they were smaller than normal [13].…”

“…Previously reported recessive MYH2 related myopathies presented with ophthalmoplegia in association with facial weakness and usually mild proximal and distal limb weakness [11][12][13]. Ptosis was seen in some cases.…”

“…Fatty infiltration was identified by muscle biopsy in several cases. Muscle MRI has been performed only in three reported cases and demonstrated fatty infiltration in some muscles, mainly in the quadriceps, semitendinosus and medial gastrocnemius [11,13].…”