title: A Novel Missense Variant in the AGRN Gene; Congenital Myasthenic Syndrome Presenting With Head Drop.
abstract: Congenital myasthenic syndromes (CMS) are a heterogeneous group of diseases of the neuromuscular junction caused by compromised synaptic transmission. Clinical features include early-onset weakness of limbs and oculobulbar muscles resulting in hypotonia, bulbar paresis, ptosis, and hypoventilation. The first dropped head syndrome in children were detected in 2 patients with LMNA and SEPN1 mutations. We report a 17-month-old boy with dropped head and limb-girdle weakness, who had no ptosis or ophthalmoplegia at presentation. We performed whole exome sequencing, which revealed a homozygous missense variant in the AGRN gene c.5023G>A, p.Gly1675Ser in the LG2 domain, which is predicted to be likely disease causing by in silico tools. Agrin is known to play a critical role in the development and maintenance of the neuromuscular junction. Agrin-related CMS is one of the rarest subtypes. Of note, our patient is the first described patient with agrin-related CMS with dropped head phenotype.
authors.affiliation: *Pediatric Neurology Unit, Hacettepe University School of Medicine, Ankara, Turkey; and †Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Mert
authors.initials: M
authors.lastname: Karakaya
authors.forename: Ozge
authors.initials: O
authors.lastname: Ceyhan-Birsoy
authors.forename: Alan H
authors.initials: AH
authors.lastname: Beggs
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloglu
mesh_terms: D018171:Agrin / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D059472:Exome; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D020294:Myasthenic Syndromes, Congenital / Q000235:genetics*
chemical_list: D018171:Agrin