Global FKRP Registry: observations in more than 300 patients with Limb Girdle Muscular Dystrophy R9

Ann Clin Transl Neurol. 2020 May;7(5):757-766. doi: 10.1002/acn3.51042. Epub 2020 Apr 28.

Abstract

Objective: The Global FKRP Registry is a database for individuals with conditions caused by mutations in the Fukutin-Related Protein (FKRP) gene: limb girdle muscular dystrophy R9 (LGMDR9, formerly LGMD2I) and congenital muscular dystrophies MDC1C, Muscle-Eye-Brain Disease and Walker-Warburg Syndrome. The registry seeks to further understand the natural history and prevalence of FKRP-related conditions; aid the rapid identification of eligible patients for clinical studies; and provide a source of information to clinical and academic communities.

Methods: Registration is patient-initiated through a secure online portal. Data, reported by both patients and their clinicians, include: age of onset, presenting symptoms, family history, motor function and muscle strength, respiratory and cardiac function, medication, quality of life and pain.

Results: Of 663 registered participants, 305 were genetically confirmed LGMDR9 patients from 23 countries. A majority of LGMDR9 patients carried the common mutation c.826C > A on one or both alleles; 67.9% were homozygous and 28.5% were compound heterozygous for this mutation. The mean ages of symptom onset and disease diagnosis were higher in individuals homozygous for c.826C > A compared with individuals heterozygous for c.826C > A. This divergence was replicated in ages of loss of running ability, wheelchair-dependence and ventilation assistance; consistent with the milder phenotype associated with individuals homozygous for c.826C > A. In LGMDR9 patients, 75.1% were currently ambulant and 24.6%, nonambulant (unreported in 0.3%). Cardiac impairment was reported in 23.2% (30/129).

Interpretation: The Global FKRP Registry enables the collection of patient natural history data, which informs academics, healthcare professionals and industry. It represents a trial-ready cohort of individuals and is centrally placed to facilitate recruitment to clinical studies.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Child
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Muscular Dystrophies, Limb-Girdle / physiopathology
  • Pentosyltransferases / genetics*
  • Phenotype
  • Registries*
  • Walker-Warburg Syndrome / genetics*
  • Walker-Warburg Syndrome / physiopathology
  • Young Adult

Substances

  • FKRP protein, human
  • Pentosyltransferases

Supplementary concepts

  • Muscular Dystrophy, Limb-Girdle, Type 2I

Grant support

This work was funded by TREAT‐NMD grants EU FP6 and LSHM‐CT‐2006‐036825; Aktion Benni und Co grant ; Deutsche Gesellschaft für Muskelkranke grant ; LGMD2i Research Fund grant ; Cure LGMD2i grant .