Newly recognized congenital myasthenic syndrome associated with high conductance and fast closure of the acetylcholine receptor channel

Andrew G Engel, O. D. Uchitel, T. J. Walls, A. Nagel, C. M. Harper, J. Bodensteiner

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

We describe here a new congenital myasthenic syndrome associated with a kinetic abnormality of the acetylcholine receptor (AChR) channel. The propositus had poor suck and cry after birth. Subsequently, she had intermittent ocular symptoms and fatigued abnormally on exertion. At age 9 years, significant weakness was detected only in the frontalis, levator palpebrae, and neck flexor muscles. Electromyography showed no decrement in limb muscles but single-fiber examination of the facial muscles was consistent with a neuromuscular transmission defect. The ocular symptoms responded partially to pyridostigmine, but the abnormal fatigability did not. Tests for anti-AChR antibodies were negative. A younger sister had elements of the same disease. An intercostal muscle specimen was obtained from the propositus at age 9 years for endplate studies. The quantal content of the endplate potential was normal. Miniature endplate currents were abnormally large and their decay time constant was abnormally short. AChR channel properties were studied by analysis of acetylcholine-induced current noise. The mean single-channel conductance was increased 1.7-fold and the mean channel open time was 30% shorter than normal. The number of AChR per endplate was normal. Electron microscopy of most endplates showed no abnormality, but a few were degenerating or simplified. The channel abnormality may stem from a point mutation in an AChR subunit affecting a single amino acid residue lining the pore of the AChR channel. The mechanism by which the physiological abnormality produces clinical symptoms is not known, but possible explanations are considered.

Original languageEnglish (US)
Pages (from-to)38-47
Number of pages10
JournalAnnals of Neurology
Volume34
Issue number1
StatePublished - 1993

Fingerprint

Congenital Myasthenic Syndromes
Cholinergic Receptors
Pyridostigmine Bromide
Intercostal Muscles
Facial Muscles
Neck Muscles
Electromyography
Point Mutation
Acetylcholine
Noise
Electron Microscopy
Extremities
Parturition
Amino Acids
Muscles
Antibodies

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Newly recognized congenital myasthenic syndrome associated with high conductance and fast closure of the acetylcholine receptor channel. / Engel, Andrew G; Uchitel, O. D.; Walls, T. J.; Nagel, A.; Harper, C. M.; Bodensteiner, J.

In: Annals of Neurology, Vol. 34, No. 1, 1993, p. 38-47.

Research output: Contribution to journalArticle

Engel, Andrew G ; Uchitel, O. D. ; Walls, T. J. ; Nagel, A. ; Harper, C. M. ; Bodensteiner, J. / Newly recognized congenital myasthenic syndrome associated with high conductance and fast closure of the acetylcholine receptor channel. In: Annals of Neurology. 1993 ; Vol. 34, No. 1. pp. 38-47.
@article{2132e2ff3f4346c98eeeb250d34c1209,
title = "Newly recognized congenital myasthenic syndrome associated with high conductance and fast closure of the acetylcholine receptor channel",
abstract = "We describe here a new congenital myasthenic syndrome associated with a kinetic abnormality of the acetylcholine receptor (AChR) channel. The propositus had poor suck and cry after birth. Subsequently, she had intermittent ocular symptoms and fatigued abnormally on exertion. At age 9 years, significant weakness was detected only in the frontalis, levator palpebrae, and neck flexor muscles. Electromyography showed no decrement in limb muscles but single-fiber examination of the facial muscles was consistent with a neuromuscular transmission defect. The ocular symptoms responded partially to pyridostigmine, but the abnormal fatigability did not. Tests for anti-AChR antibodies were negative. A younger sister had elements of the same disease. An intercostal muscle specimen was obtained from the propositus at age 9 years for endplate studies. The quantal content of the endplate potential was normal. Miniature endplate currents were abnormally large and their decay time constant was abnormally short. AChR channel properties were studied by analysis of acetylcholine-induced current noise. The mean single-channel conductance was increased 1.7-fold and the mean channel open time was 30{\%} shorter than normal. The number of AChR per endplate was normal. Electron microscopy of most endplates showed no abnormality, but a few were degenerating or simplified. The channel abnormality may stem from a point mutation in an AChR subunit affecting a single amino acid residue lining the pore of the AChR channel. The mechanism by which the physiological abnormality produces clinical symptoms is not known, but possible explanations are considered.",
author = "Engel, {Andrew G} and Uchitel, {O. D.} and Walls, {T. J.} and A. Nagel and Harper, {C. M.} and J. Bodensteiner",
year = "1993",
language = "English (US)",
volume = "34",
pages = "38--47",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "1",

}

TY - JOUR

T1 - Newly recognized congenital myasthenic syndrome associated with high conductance and fast closure of the acetylcholine receptor channel

AU - Engel, Andrew G

AU - Uchitel, O. D.

AU - Walls, T. J.

AU - Nagel, A.

AU - Harper, C. M.

AU - Bodensteiner, J.

PY - 1993

Y1 - 1993

N2 - We describe here a new congenital myasthenic syndrome associated with a kinetic abnormality of the acetylcholine receptor (AChR) channel. The propositus had poor suck and cry after birth. Subsequently, she had intermittent ocular symptoms and fatigued abnormally on exertion. At age 9 years, significant weakness was detected only in the frontalis, levator palpebrae, and neck flexor muscles. Electromyography showed no decrement in limb muscles but single-fiber examination of the facial muscles was consistent with a neuromuscular transmission defect. The ocular symptoms responded partially to pyridostigmine, but the abnormal fatigability did not. Tests for anti-AChR antibodies were negative. A younger sister had elements of the same disease. An intercostal muscle specimen was obtained from the propositus at age 9 years for endplate studies. The quantal content of the endplate potential was normal. Miniature endplate currents were abnormally large and their decay time constant was abnormally short. AChR channel properties were studied by analysis of acetylcholine-induced current noise. The mean single-channel conductance was increased 1.7-fold and the mean channel open time was 30% shorter than normal. The number of AChR per endplate was normal. Electron microscopy of most endplates showed no abnormality, but a few were degenerating or simplified. The channel abnormality may stem from a point mutation in an AChR subunit affecting a single amino acid residue lining the pore of the AChR channel. The mechanism by which the physiological abnormality produces clinical symptoms is not known, but possible explanations are considered.

AB - We describe here a new congenital myasthenic syndrome associated with a kinetic abnormality of the acetylcholine receptor (AChR) channel. The propositus had poor suck and cry after birth. Subsequently, she had intermittent ocular symptoms and fatigued abnormally on exertion. At age 9 years, significant weakness was detected only in the frontalis, levator palpebrae, and neck flexor muscles. Electromyography showed no decrement in limb muscles but single-fiber examination of the facial muscles was consistent with a neuromuscular transmission defect. The ocular symptoms responded partially to pyridostigmine, but the abnormal fatigability did not. Tests for anti-AChR antibodies were negative. A younger sister had elements of the same disease. An intercostal muscle specimen was obtained from the propositus at age 9 years for endplate studies. The quantal content of the endplate potential was normal. Miniature endplate currents were abnormally large and their decay time constant was abnormally short. AChR channel properties were studied by analysis of acetylcholine-induced current noise. The mean single-channel conductance was increased 1.7-fold and the mean channel open time was 30% shorter than normal. The number of AChR per endplate was normal. Electron microscopy of most endplates showed no abnormality, but a few were degenerating or simplified. The channel abnormality may stem from a point mutation in an AChR subunit affecting a single amino acid residue lining the pore of the AChR channel. The mechanism by which the physiological abnormality produces clinical symptoms is not known, but possible explanations are considered.

UR - http://www.scopus.com/inward/record.url?scp=0027256322&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027256322&partnerID=8YFLogxK

M3 - Article

C2 - 7685992

AN - SCOPUS:0027256322

VL - 34

SP - 38

EP - 47

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 1

ER -