Send to

Choose Destination
Am J Med Genet A. 2018 Jul;176(7):1594-1601. doi: 10.1002/ajmg.a.38707. Epub 2018 Apr 28.

Recessive variants of MuSK are associated with late onset CMS and predominant limb girdle weakness.

Author information

Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
Service of Neuromuscular Disorders, Division of Neurology, Department of Internal Medicine, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.
Bio-Prodict, Nijmegen, The Netherlands.
Unidade de Neurologia Clínica, Hospital de Base do Distrito Federal, Brasília, Brazil.
Serviço de Neurologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
Friedrich-Baur-Institut, Ludwig-Maximilians-University Munich, Munich, Germany.
CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany.


Congenital myasthenic syndrome (CMS) is a heterogeneous disorder that causes fatigable muscle weakness. CMS has been associated with variants in the MuSK gene and, to date, 16 patients have been reported. MuSK-CMS patients present a different phenotypic pattern of limb girdle weakness. Here, we describe four additional patients and discuss the phenotypic and clinical relationship with those previously reported. Two novel damaging missense variants are described: c.1742T > A; p.I581N found in homozygosis, and c.1634T > C; p.L545P found in compound heterozygosis with p.R166*. The reported patients had predominant limb girdle weakness with symptom onset at 12, 17, 18, and 30 years of age, and the majority exhibited a good clinical response to Salbutamol therapy, but not to esterase inhibitors. Meta-analysis including previously reported variants revealed an increased likelihood of a severe, respiratory phenotype with null alleles. Missense variants exclusively affecting the kinase domain, but not the catalytic site, are associated with late onset. These data refine the phenotype associated with MuSK-related CMS.


congenital myasthenic syndrome; late onset; limb girdle; muscle-specific kinase

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center