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

• Published in: Neuromuscular disorders : NMD 2020-01, Vol.30 (1), p.54-58
• Main Authors: Moreno, Cristiane Araújo Martins, Estephan, Eduardo de Paula, Fappi, Alan, Monges, Soledad, Lubieniecki, Fabiana, Lopes Abath Neto, Osório, Reed, Umbertina Conti, Donkervoort, Sandra, Harms, Matthew B., Bonnemann, Carsten, Zanoteli, Edmar
• Format: Article
• Language: English
• Subjects: Adolescent; CFTD; Child; Congenital myopathy; Dropped head; Female; Genetic Association Studies; Humans; Myopathies, Structural, Congenital - genetics; Myopathies, Structural, Congenital - physiopathology; Recessive inheritance; TPM3; Tropomyosin - genetics
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2019.11.001

•Homozygous mutations on TPM3 gene can lead to mild presentations of congenital fiber type disproportion myopathy.•Dropped-head can be present in TPM3-related myopathies.•Aminoacid-polarity changes nearby actin-binding sites are predicted to cause muscle dysfunction. Congenital fiber type disproportion (CFTD) is a rare congenital myopathy subtype defined by slow type 1 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 a few reports of recessive loss-of-function mutations in TPM3 causing severe Nemaline Myopathy and CFTD. We present two patients harboring TPM3 mutations. The first is a novel homozygous missense variant with a mild CFTD clinical phenotype inherited in a recessive fashion. The second is a previously reported heterozygous mutation presenting within pronounced early axial involvement and dropped head. This report expands the genotype-phenotype correlation in the TPM3 myopathy showing a recessive mutation causing a mild clinical phenotype and also shows that TPM3 mutations should be part of the investigation in patients with dropped head.