Abstract
08P SRPK3-TTN related myopathy: early clinical characteristics and muscle imaging findings
Neuromuscular disorders : NMD, Vol.43(Supplement 1), p.55
10/2024
DOI: 10.1016/j.nmd.2024.07.215
Abstract
SRPK3-TTN-related myopathy was recently established as a neuromuscular disorder inherited through digenic transmission. Here, we present clinical findings from four new pediatric cases (age range: 3-9 years; all males) diagnosed with SRPK3-TTN-related myopathy with a truncating TTN-variant and a concomitant pathogenic variant in the X-chromosomal SRPK3. All four newly identified patients presented before birth with reduced fetal movements. At birth, three patients had contractures and hypotonia, and one had respiratory involvement. Motor developmental delay and muscle weakness were evident in all patients during their first year of life. Independent ambulation was achieved between 1.5-4 years (P1-P3) while P4 has not attained independent ambulation yet (3.8 years). P1 was diagnosed with respiratory insufficiency (forced vital capacity: 57% of predicted, age 9 years). None of the patients showed cardiac involvement at their last evaluation. Muscle imaging (P2 and P3) revealed features consistent with titinopathy, including dense, deep layers of echogenicity in the triceps and paraspinal muscles (on ultrasound), and mild fibroadipose transformation of the thigh muscles, with striking selective involvement of the semitendinosus muscle (on ultrasound and MRI). P1 had two muscle biopsies, both with myopathic changes, marked by significant variation in fiber size, increased centrally placed nuclei, and predominance of type-1 fibers. The first biopsy (age 7 months) suggested rod-like structures on GT, not confirmed on electron microscopy, and the subsequent biopsy (age 13 years) was consistent with central core myopathy. This work highlights early clinical manifestations of SRPK3-TTN-related myopathy and highlights muscle imaging patterns that resemble those observed in monogenic titinopathy cases. These features should help with the potentially challenging variant interpretation in digenic TTN/SRPK3 disease and allow for a confident diagnosis of this novel condition.
Details
- Title: Subtitle
- 08P SRPK3-TTN related myopathy: early clinical characteristics and muscle imaging findings
- Creators
- R. Orbach - National Institute of Neurological Disorders and StrokeS. Donkervoort - National Institute of Neurological Disorders and StrokeD. Saade - Department of Neurology, University of Iowa, Carver College of Medicine, Iowa City, USAP. D'Souza - National Human Genome Research InstituteJ. Haugland - National Institute of Neurological Disorders and StrokeA. Foley - National Institute of Neurological Disorders and StrokeD. Bharucha Goebel - National Institute of Neurological Disorders and StrokeA. Potticary - National Institute of Neurological Disorders and StrokeK. Chao - Broad InstituteE. Macnamara - National Human Genome Research InstituteR. Finkel - St. Jude Children's Research HospitalA. Beggs - Boston Children's HospitalC. Tifft - National Human Genome Research InstituteC. Bönnemann - National Institute of Neurological Disorders and Stroke
- Resource Type
- Abstract
- Publication Details
- Neuromuscular disorders : NMD, Vol.43(Supplement 1), p.55
- DOI
- 10.1016/j.nmd.2024.07.215
- ISSN
- 0960-8966
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 10/2024
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984721236702771
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