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Am J Med Genet A. 2019 Apr;179(4):655-658. doi: 10.1002/ajmg.a.61060. Epub 2019 Feb 4.

Isolated vocal cord paralysis in two siblings with compound heterozygous variants in MUSK: Expanding the phenotypic spectrum.

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Department of Pediatrics, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Department of Pediatrics, Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.


The congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by perturbations in signal transduction at the neuromuscular junction. Defects in muscle, skeletal, receptor tyrosine kinase (MuSK) cause two distinct phenotypes: fetal akinesia with multiple congenital anomalies (Fetal akinesia deformation sequence [MIM:208150]) and early onset congenital myasthenia (myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency [MIM:616325]). Myasthenia due to MuSK deficiency has variable clinical features, ranging from a milder presentation of isolated late-onset proximal muscle weakness; to a severe presentation of prenatal-onset diffuse weakness, ophthalmoplegia, respiratory failure, and vocal cord paralysis (VCP). Here, we propose to expand the phenotypic spectrum for MuSK deficiency to include isolated VCP with the absence of other classical myasthenic symptoms. We evaluated two brothers who presented in the neonatal period with respiratory failure secondary to isolated VCP. Research-based exome sequencing revealed biallelic likely pathogenic variants in MUSK (MIM:601296). Both children had normal gross motor and fine motor development. One brother had speech delay, likely due to a combination of tracheostomy status and ankyloglossia. This case report suggests that CMS should be on the differential diagnosis for familial recurrence of VCP.


Dok-7 deficiency; MuSK deficiency; congenital myasthenic syndromes; phenotypic expansion; vocal cord paralysis


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