Novel Radiological Brain Anomalies in a Patient with Congenital Muscular Dystrophy due to FKRP Mexican Founder Mutation c.1387A > G: Review of the Literature

Marivi Cervera-Gaviria; Julia Enterría-Rosales; Juan José Juárez-Vignon-Whaley; Julián García-Sánchez; Rodrigo Treviño-Velasco; Jaime Cervera-Gaviria

doi:10.1055/s-0041-1726470

Journal of Pediatric Genetics, Table of Contents

J Pediatr Genet 2023; 12(03): 237-241
DOI: 10.1055/s-0041-1726470

Case Based Review

Novel Radiological Brain Anomalies in a Patient with Congenital Muscular Dystrophy due to FKRP Mexican Founder Mutation c.1387A > G: Review of the Literature

Marivi Cervera-Gaviria

¹Department of Genetics, The American British Cowdray Hospital, Mexico City, Mexico

,

Julia Enterría-Rosales

²School of Medicine, Instituto Tecnológico de Monterrey, Monterrey, Mexico

,

Juan José Juárez-Vignon-Whaley

³School of Medicine, Anáhuac University Mexico, Mexico City, Mexico

,

Julián García-Sánchez

³School of Medicine, Anáhuac University Mexico, Mexico City, Mexico

,

Rodrigo Treviño-Velasco

³School of Medicine, Anáhuac University Mexico, Mexico City, Mexico

,

Jaime Cervera-Gaviria

⁴Department of Internal Medicine, Sociedad de Beneficiencia Española CDMX, Mexico City, Mexico

› Author Affiliations

Abstract

Mutations in the FKRP gene result in phenotypes with severe forms of congenital muscular dystrophies (CMD) and limb-girdle muscular dystrophies. We present a Mexican patient with a pathogenic homozygous mutation in the FKRP gene (c.1387A > G, p.Asn463Asp) and CMD with radiological brain anomalies as disseminated hyperintensity lesions and discrete generalized cortical atrophy. These findings have not been reported to the best of our knowledge in other patients with the same mutation. The mutation c.1387A > G, p.Asn463Asp in the FKRP gene has been described to have a founder effect in central Mexico, since all the patients described to date are of Hispanic origin. Therefore, we emphasize studying mutations in the FKRP gene in Hispanic pediatric patients with clinical suspicion of CMD. Clinical and molecular diagnosis of specific CMD subtypes is needed to help clarify the prognosis, management, and genetic counseling to the patient and families.

Keywords

FKRP gene - congenital muscular dystrophy - founder mutation

Full Text

References

References
1 Sparks SE, Escolar DM. Congenital muscular dystrophies. Handb Clin Neurol 2011; 101: 47-79
2 Quijano S, Gómez M. Distrofias musculares congénitas. Rev Med Clin Las Condes 2018; 29 (05) 530-543
3 Cataldi MP, Blaeser A, Lu P, Leroy V, Lu QL. ISPD overexpression enhances Ribitol-induced glycosylation of α-dystroglycan in dystrophic FKRP mutant mice. Mol Ther Methods Clin Dev 2019; 17: 271-280
4 Gumlaw N, Sevigny LM, Zhao H. et al. biAb mediated restoration of the linkage between dystroglycan and laminin-211 as a therapeutic approach for α-dystroglycanopathies. Mol Ther 2020; 28 (02) 664-676
5 Lee AJ, Jones KA, Butterfield RJ. et al. Clinical, genetic, and pathologic characterization of FKRP Mexican founder mutation c.1387A>G. Neurol Genet 2019; 5 (02) e315
6 Gonzalez-Perez P, Smith C, Sebetka WL, Gedlinske A, Perlman S, Mathews KD. Clinical and electrophysiological evaluation of myasthenic features in an alpha-dystroglycanopathy cohort (FKRP-predominant). Neuromuscul Disord 2020; 30 (03) 213-218
7 Cohn RD. Dystroglycan: important player in skeletal muscle and beyond. Neuromuscul Disord 2005; 15 (03) 207-217
8 Esapa CT, McIlhinney RA, Blake DJ. Fukutin-related protein mutations that cause congenital muscular dystrophy result in ER-retention of the mutant protein in cultured cells. Hum Mol Genet 2005; 14 (02) 295-305
9 Fu X-N, Xiong H. Genetic and clinical advances of congenital muscular dystrophy. Chin Med J (Engl) 2017; 130 (21) 2624-2631
10 Kim J, Lana B, Torelli S. et al. A new patient-derived iPSC model for dystroglycanopathies validates a compound that increases glycosylation of α-dystroglycan. EMBO Rep 2019; 20 (11) e47967
11 Brockington M, Blake DJ, Prandini P. et al. Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha2 deficiency and abnormal glycosylation of alpha-dystroglycan. Am J Hum Genet 2001; 69 (06) 1198-1209
12 MacLeod H, Pytel P, Wollmann R. et al. A novel FKRP mutation in congenital muscular dystrophy disrupts the dystrophin glycoprotein complex. Neuromuscul Disord 2007; 17 (04) 285-289
13 Navarro-Cobos MJ, González-Del Angel A, Estandia-Ortega B. et al. Molecular analysis confirms that FKRP related disorders are underdiagnosed in Mexican patients with neuromuscular diseases. Neuropediatrics 2017; 48 (06) 442-450
14 Angelini C, Pinzan E. Advances in imaging of brain abnormalities in neuromuscular disease. Ther Adv Neurol Disorder 2019; 12: 1756286419845567
15 Butterfield RJ. Congenital muscular dystrophy and congenital myopathy. Continuum (Minneap Minn) 2019; 25 (06) 1640-1661
16 Klein A, Clement E, Mercuri E, Muntoni F. Differential diagnosis of congenital muscular dystrophies. Eur J Paediatr Neurol 2008; 12 (05) 371-377
17 Mah JK, Korngut L, Fiest KM. et al. A systematic review and meta-analysis on the epidemiology of the muscular dystrophies. Can J Neurol Sci 2016; 43 (01) 163-177
18 Peat RA, Smith JM, Compton AG. et al. Diagnosis and etiology of congenital muscular dystrophy. Neurology 2008; 71 (05) 312-321
19 Lim BC, Lee S, Shin JY. et al. Molecular diagnosis of congenital muscular dystrophies with defective glycosylation of alpha-dystroglycan using next-generation sequencing technology. Neuromuscul Disord 2013; 23 (04) 337-344
20 Benarroch L, Bonne G, Rivier F, Hamroun D. The 2020 version of the gene table of neuromuscular disorders (nuclear genome). Neuromuscul Disord 2019; 29 (12) 980-1018
21 Dowling JJ, Gonorazky HD, Cohn RD, Campbell C. Treating pediatric neuromuscular disorders: The future is now. Am J Med Genet A 2018; 176 (04) 804-841
22 Calvert LD, McKeever TM, Kinnear WJ, Britton JR. Trends in survival from muscular dystrophy in England and Wales and impact on respiratory services. Respir Med 2006; 100 (06) 1058-1063