Epidemiology and natural history in 101 subjects with FKRP-related limb-girdle muscular dystrophy R9. The Norwegian LGMDR9 cohort study (2020)

Synnøve M Jensen; Kai Ivar Müller; Svein Ivar Mellgren; Laurence A Bindoff; Magnhild Rasmussen; Kristin Ørstavik; Christoffer Jonsrud; Kristian Tveten; Øivind Nilssen; Marijke Van Ghelue; Kjell Arne Arntzen

doi:10.1016/j.nmd.2022.11.005

Epidemiology and natural history in 101 subjects with FKRP-related limb-girdle muscular dystrophy R9. The Norwegian LGMDR9 cohort study (2020)

Neuromuscul Disord. 2023 Feb;33(2):119-132. doi: 10.1016/j.nmd.2022.11.005. Epub 2022 Nov 25.

Affiliations

¹ National Neuromuscular Centre Norway and Department of Neurology, University Hospital of North Norway HF, Tromsø, PO Box 100, N-9038, Tromsø, Norway; Department of Clinical Medicine, University of Tromsø - The Artic University of Norway, PO Box 6050 Langnes, N-9037, Tromsø, Norway. Electronic address: synnove.magnhild.jensen@unn.no.
² National Neuromuscular Centre Norway and Department of Neurology, University Hospital of North Norway HF, Tromsø, PO Box 100, N-9038, Tromsø, Norway; Department of Clinical Medicine, University of Tromsø - The Artic University of Norway, PO Box 6050 Langnes, N-9037, Tromsø, Norway; Department of Neurology, Hospital of Southern Norway, PO box 416 Lundsiden, 4604, Kristiansand S, Norway.
³ National Neuromuscular Centre Norway and Department of Neurology, University Hospital of North Norway HF, Tromsø, PO Box 100, N-9038, Tromsø, Norway; Department of Clinical Medicine, University of Tromsø - The Artic University of Norway, PO Box 6050 Langnes, N-9037, Tromsø, Norway.
⁴ Department of Clinical Medicine (K1), University of Bergen, N-5021, Bergen, Norway; Department of Neurology, Haukeland University Hospital, PO Box 1400, N-5021, Bergen, Norway; National Unit of Newborn Screening and Advanced Laboratory Diagnostics, Oslo University Hospital, PO Box 4950 Nydalen, N-0424, Oslo, Norway.
⁵ Department of Clinical Neurosciences for Children, Oslo University Hospital, PO Box 4950 Nydalen, N-0424, Oslo, Norway; Unit for Congenital and Hereditary Neuromuscular Conditions (EMAN), Department of Neurology, Oslo University Hospital, PO Box 4950 Nydalen, N-0424, Oslo, Norway.
⁶ Unit for Congenital and Hereditary Neuromuscular Conditions (EMAN), Department of Neurology, Oslo University Hospital, PO Box 4950 Nydalen, N-0424, Oslo, Norway.
⁷ Department of Medical Genetics, Division of Child and Adolescent Health, University Hospital of North Norway HF, PO Box 55, N-9038, Tromsø, Norway.
⁸ Department of Medical Genetics, Telemark Hospital Trust, PO Box 2900 Kjørbekk, N-3710, Skien, Norway.
⁹ Department of Clinical Medicine, University of Tromsø - The Artic University of Norway, PO Box 6050 Langnes, N-9037, Tromsø, Norway; Department of Medical Genetics, Division of Child and Adolescent Health, University Hospital of North Norway HF, PO Box 55, N-9038, Tromsø, Norway.

PMID: 36522254
DOI: 10.1016/j.nmd.2022.11.005

Abstract

We aimed to investigate the epidemiology and natural history of FKRP-related limb-girdle muscular dystrophy R9 (LGMDR9) in Norway. We identified 153 genetically confirmed subjects making the overall prevalence 2.84/100,000, the highest reported figure worldwide. Of the 153 subjects, 134 (88 %) were homozygous for FKRP c.826C>A giving a carrier frequency for this variant of 1/101 in Norway. Clinical questionnaires and patient notes from 101 subjects, including 88 c.826C>A homozygotes, were reviewed, and 43/101 subjects examined clinically. Age of onset in c.826C>A homozygotes demonstrated a bimodal distribution. Female subjects showed an increased cumulative probability of wheelchair dependency and need for ventilatory support. Across the cohort, the need for ventilatory support preceded wheelchair dependency in one third of the cases, usually due to sleep apnea. In c.826C>A homozygotes, occurrence of cardiomyopathy correlated positively with male gender but not with age or disease stage. This study highlights novel gender differences in both loss of ambulation, need for ventilatory support and the development of cardiomyopathy. Our results confirm the need for vigilance in order to detect respiratory insufficiency and cardiac involvement, but indicate that these events affect males and females differently.

Keywords: Cardiomyopathy; FKRP; Fukutin-related protein; Gender-related LGMDR9 differences; Limb-girdle muscular dystrophies; Prevalence.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Female
Homozygote
Humans
Male
Muscular Dystrophies, Limb-Girdle* / diagnosis
Muscular Dystrophies, Limb-Girdle* / epidemiology
Muscular Dystrophies, Limb-Girdle* / genetics
Norway / epidemiology
Pentosyltransferases
Respiratory Insufficiency*

Substances

FKRP protein, human
Pentosyltransferases