Congenital fiber type disproportion caused by TPM3 mutation: a report of two atypical cases.

Abstract Congenital fiber type disproportion (CFTD) is a rare congenital myopathy subtype defined by slow-type1 hypotrophy in the absence of any other major structural findings such as, rods central nuclei or cores. Dominant missense changes in slow alpha-tropomyosin coded by TPM3 gene are the main cause of the CFTD. There are only few reports of recessive loss of function mutations in TPM3 causing severe Nemaline Myopathy and Fiber Type Disproportion. Here, we presented two patients harboring TPM3 mutations. The first is a novel homozygous missense variant with a mild CFTD phenotype inherited in recessive fashion. The second is a previously reported heterozygous mutation presenting within pronounced early axial involvement and drop head. This report expanded the genotype-phenotype with the TPM3 myopathy showing a recessive mutation causing a mild phenotype and also show that TPM3 gene should be part of the differential diagnosis for patients with dropped head.