Titin related myopathy with ophthalmoplegia. A novel phenotype

Issa Alawneh; Kyoko E Yuki; Kimberly Amburgey; Grace Yoon; James J Dowling; Lili-Naz Hazrati; Hernan Gonorazky

doi:10.1016/j.nmd.2023.05.003

Titin related myopathy with ophthalmoplegia. A novel phenotype

Neuromuscul Disord. 2023 Jul;33(7):605-609. doi: 10.1016/j.nmd.2023.05.003. Epub 2023 May 13.

Authors

Issa Alawneh¹, Kyoko E Yuki², Kimberly Amburgey³, Grace Yoon⁴, James J Dowling⁵, Lili-Naz Hazrati⁶, Hernan Gonorazky⁷

Affiliations

¹ Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
² Division of Genome Diagnostics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
³ Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada; Division of Genome Diagnostics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
⁴ Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada; Division of Genetic, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
⁵ Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada; Division of Genetic, The Hospital for Sick Children, University of Toronto, Toronto, Canada; Program of Genetic and Genome Biology, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
⁶ Division of Pathology, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
⁷ Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada; Program of Genetic and Genome Biology, The Hospital for Sick Children, University of Toronto, Toronto, Canada. Electronic address: [email protected].

PMID: 37393749
DOI: 10.1016/j.nmd.2023.05.003

Abstract

Titin-related myopathy is an emerging genetic neuromuscular disorder with a wide spectrum of clinical phenotypes. To date, there have not been reports of patients with this disease that presented with extraocular muscle involvement. Here we discuss a 19-year-old male with congenital weakness, complete ophthalmoplegia, thoracolumbar scoliosis, and obstructive sleep apnea. Muscle magnetic resonance imaging revealed severe involvement of the gluteal and anterior compartment muscles, and clear adductor sparing, while muscle biopsy of the right vastus lateralis showed distinctive cap-like structures. Trio Whole Exome Sequencing (WES) showed compound heterozygous likely pathologic variants in the TTN gene. (c.82541_82544dup (p.Arg27515Serfs*2) in exon 327 (NM_001267550.2) and c.31846+1G>A (p.?) in exon 123 (NM_001267550.2). To our knowledge, this is the first report of a TTN-related disorder associated with ophthalmoplegia.

Keywords: Congenital myopathy; Ophthalmoplegia; Titinopathy.

Publication types

Case Reports

MeSH terms

Connectin / genetics
Humans
Male
Muscle, Skeletal / pathology
Muscular Diseases* / genetics
Muscular Diseases* / pathology
Mutation
Neuromuscular Diseases* / pathology
Ophthalmoplegia* / genetics
Ophthalmoplegia* / pathology
Phenotype
Young Adult

Substances

Connectin
TTN protein, human