A pathogenic CTBP1 variant featuring HADDTS with dystrophic myopathology.

HADDTS (Hypotonia, Ataxia, Developmental-Delay and Tooth-enamel defects) is a newly emerging syndrome caused by CTBP1 mutations. Only five reports (13 cases) are available; three contained muscle-biopsy results but none presented illustrated histomyopathology. We report a patient in whom whole-exome sequencing revealed a heterozygous de novo CTBP1 missense mutation (c.1024 C>T; p.(Arg342Trp)). Progressive muscular weakness and myopathic electromyography suggested a myopathological substrate; muscle-biopsy revealed dystrophic features with endomysial-fibrosis, fiber-size variability, necrotic/degenerative vacuolar myopathy, sarcoplasmic/myofibrillar- and striation-alterations, and enzyme histochemical and structural mitochondrial alterations/defects including vacuolar mitochondriopathy. Our report expands the number of cases in this extremely rare condition and provides illustrated myopathology, muscle-MRI, and electron-microscopy. These are crucial for elucidating the nature and extent of the underlying myopathological-correlates and to characterize the myopatholgical phenotype spectrum in this genetic neurodevelopmental condition. Copyright © 2023. Published by Elsevier B.V.

Citation

Hazim Kadhim, Eliane El-Howayek, Sandra Coppens, Jennifer Duff, Ana Topf, Jean-Paul Kaleeta, Paolo Simoni, Grammatina Boitsios, Gauthier Remiche, Volker Straub, Catheline Vilain, Nicolas Deconinck. A pathogenic CTBP1 variant featuring HADDTS with dystrophic myopathology. Neuromuscular disorders : NMD. 2023 May;33(5):410-416

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PMID: 37037050

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