J Pediatr Genet 2022; 11(02): 144-146
DOI: 10.1055/s-0040-1715640
Case Report

A Truncating Variant of CHRNG as a Cause of Escobar Syndrome: A Multiple Pterygium Syndrome Subtype

1   Department of Pediatrics, University of Arizona College of Medicine, Tucson, Arizona, United States
2   Section of Neurology and Developmental Neurosciences, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States
,
Shalinkumar Patel
1   Department of Pediatrics, University of Arizona College of Medicine, Tucson, Arizona, United States
,
Mohammad Y. Bader
1   Department of Pediatrics, University of Arizona College of Medicine, Tucson, Arizona, United States
,
1   Department of Pediatrics, University of Arizona College of Medicine, Tucson, Arizona, United States
› Author Affiliations
Funding None.

Abstract

Escobar syndrome is a milder variant of multiple pterygium syndrome characterized by pterygia, scoliosis, and multiple congenital contractures. It is most frequently due to a genetic variant in CHRNG, which encodes the γ-subunit of the nicotinic acetylcholine receptor. Though the subunit is considered a “fetal” form and transitions to the “adult” ε-subunit by 33 weeks' gestation, the pathogenic musculoskeletal effects during fetal development render children with this condition permanently affected. We report a neonate with homozygous CHRNG c.117dupC and discuss some of the downstream clinical effects we observed with this variant.

Ethical Approval

Parental permission was obtained for publication.


Supplementary Material



Publication History

Received: 18 March 2020

Accepted: 15 July 2020

Article published online:
26 August 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Dahan-Oliel N, Cachecho S, Barnes D. et al. International multidisciplinary collaboration toward an annotated definition of arthrogryposis multiplex congenita. Am J Med Genet C Semin Med Genet 2019; 181 (03) 288-299
  • 2 Penchaszadeh VB, Salszberg B. Multiple pterygium syndrome. J Med Genet 1981; 18 (06) 451-455
  • 3 Chen H, Chang CH, Misra RP, Peters HA, Grijalva NS, Opitz JM. Multiple pterygium syndrome. Am J Med Genet 1980; 7 (02) 91-102
  • 4 Escobar V, Bixler D, Gleiser S, Weaver DD, Gibbs T. Multiple pterygium syndrome. Am J Dis Child 1978; 132 (06) 609-611
  • 5 Robinson KG, Viereck MJ, Margiotta MV, Gripp KW, Abdul-Rahman OA, Akins RE. Neuromotor synapses in Escobar syndrome. Am J Med Genet A 2013; 161A (12) 3042-3048
  • 6 Hall ZW, Sanes JR. Synaptic structure and development: the neuromuscular junction. Cell 1993; 72: 99-121
  • 7 Claudio T, Ballivet M, Patrick J, Heinemann S. Nucleotide and deduced amino acid sequences of Torpedo californica acetylcholine receptor gamma subunit. Proc Natl Acad Sci U S A 1983; 80 (04) 1111-1115
  • 8 Hesselmans LF, Jennekens FG, Van den Oord CJ, Veldman H, Vincent A. Development of innervation of skeletal muscle fibers in man: relation to acetylcholine receptors. Anat Rec 1993; 236 (03) 553-562
  • 9 Gu Y, Hall ZW. Immunological evidence for a change in subunits of the acetylcholine receptor in developing and denervated rat muscle. Neuron 1988; 1 (02) 117-125
  • 10 Martinou JC, Falls DL, Fischbach GD, Merlie JP. Acetylcholine receptor-inducing activity stimulates expression of the epsilon-subunit gene of the muscle acetylcholine receptor. Proc Natl Acad Sci U S A 1991; 88 (17) 7669-7673
  • 11 Sapru MK, Florance SK, Kirk C, Goldman D. Identification of a neuregulin and protein-tyrosine phosphatase response element in the nicotinic acetylcholine receptor epsilon subunit gene: regulatory role of an Rts transcription factor. Proc Natl Acad Sci U S A 1998; 95 (03) 1289-1294
  • 12 Hammond E, Donnenfeld AE. Fetal akinesia. Obstet Gynecol Surv 1995; 50 (03) 240-249
  • 13 Rink BD. Arthrogryposis: a review and approach to prenatal diagnosis. Obstet Gynecol Surv 2011; 66 (06) 369-377
  • 14 Chen CP. Prenatal diagnosis and genetic analysis of fetal akinesia deformation sequence and multiple pterygium syndrome associated with neuromuscular junction disorders: a review. Taiwan J Obstet Gynecol 2012; 51 (01) 12-17
  • 15 Hall JG. Pena-Shokeir phenotype (fetal akinesia deformation sequence) revisited. Birth Defects Res A Clin Mol Teratol 2009; 85 (08) 677-694
  • 16 Laquérriere A, Maluenda J, Camus A. et al. Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects. Hum Mol Genet 2014; 23 (09) 2279-2289