Conflict of interest: none.
Neuromotor synapses in Escobar syndrome
Article first published online: 16 AUG 2013
© 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 12, pages 3042–3048, December 2013
How to Cite
2013. Neuromotor synapses in Escobar syndrome. Am J Med Genet Part A 161A:3042–3048., , , , , .
- Issue published online: 19 NOV 2013
- Article first published online: 16 AUG 2013
- Manuscript Accepted: 10 JUN 2013
- Manuscript Received: 7 MAR 2013
- Nemours Foundation
- Swank Foundation
- NIH-NIGMS COBRE Program. Grant Number: P20-GM-103464
- Escobar syndrome;
- multiple pterygium syndrome;
- acetylcholine receptor;
- neuromuscular junction
The Escobar variant of multiple pterygium syndrome (OMIM #265000) is a rare, autosomal recessive disorder associated with mutations in the γ-subunit of the nicotinic acetylcholine receptor (CHRNG). CHRNG is expressed in fetal muscle during motor development and contributes to the formation of neuromuscular junctions (NMJs). Anomalies in NMJ structure and function have not been investigated in patients with Escobar syndrome. We report five patients identified as having Escobar syndrome, from four families. In three families, the same mutation (c.459dupA) was identified in CHRNG. A biopsy from brachioradialis muscle was collected from a patient from one of these families and analyzed for NMJ organization using fluorescence microscopy. Compared to spinalis muscle from control patients with idiopathic scoliosis or cerebral palsy (CP), the patient with Escobar syndrome had a significantly higher degree of acetylcholine receptor present outside acetylcholinesterase and significantly less acetylcholinesterase outside acetylcholine receptors. Given the role of the acetylcholine receptor γ-subunit in fetal neuromuscular signal transduction and in establishing the primary encounter of muscle and motor nerve terminal, the CHRNG mutations described in Escobar syndrome may cause a broader disruption of postsynaptic proteins and result in aberrant development of the NMJ due to impaired prenatal neuromuscular transmission and/or abnormal neuromuscular synaptogenesis. © 2013 Wiley Periodicals, Inc.