A very rare cause of arthrogryposis multiplex congenita: a novel mutation in TOR1A

Emre Sarıkaya; Fırat Özçelik; Ülkü Gül Şiraz; Nihal Hatipoglu; Tamer Güneş; Munis Dündar

doi:10.1515/jpem-2021-0766

Article

A very rare cause of arthrogryposis multiplex congenita: a novel mutation in TOR1A

Emre Sarıkaya , Fırat Özçelik , Ülkü Gül Şiraz , Nihal Hatipoglu , Tamer Güneş and Munis Dündar

Published/Copyright: March 16, 2022

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 35 Issue 6

Abstract

Objectives

Arthrogryposis multiplex congenita-5 (AMC5) is an autosomal recessive disease caused by homozygous or compound heterozygous mutations in the TOR1A gene on chromosome 9q34. Congenital multiple joint contractures with microcephaly, typical facial dysmorphism, developmental delay, strabismus, tremor, and increased tone are the main characteristics defined in seven patients thus far. One third of the individuals with monoallelic mutations of the gene develop isolated early-onset dystonia (DYT1 dystonia), which is inherited in an autosomal dominant fashion, with variable expressivity and incomplete penetrance. We believe that different inheritance patterns of the same gene resulting in different phenotypes will provide an opportunity to understand other similar disease groups and different aspects of gene functions.

Case presentation

We present a case with severe arthrogryposis multiplex congenita, respiratory failure, and feeding difficulties, with additional hitherto unreported symptoms, such as spontaneous bone fracture, sliding esophageal hernia, and uterine prolapse. The patient carried a novel homozygous variant (c.835delA, p.Lys275Asnfs*3) in the TOR1A gene (NM_000113.2).

Conclusions

We want to contribute to the phenotypic and genotypic spectra of this extremely rare disease.

Keywords: arthrogryposis multiplex congenita; dystonia; TOR1A ; torsinA

Corresponding author: Emre Sarıkaya, MD, Department of Pediatric Endocrinology, School of Medicine, Erciyes University, Köşk Mahallesi, Prof. Dr. Turhan Feyzioğlu Caddesi No: 42, Melikgazi, 38039, Kayseri, Turkey, Phone: +90 530 783 41 45, +90 352 207 66 66 -Ext. 25280, Fax: +90 352 437 58 25, E-mail: sarikaya.emre@gmail.com

Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The local Institutional Review Board deemed the study exempt from review.

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Received: 2021-12-22

Accepted: 2022-02-19

Published Online: 2022-03-16

Published in Print: 2022-06-27

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https://doi.org/10.1515/jpem-2021-0766

Keywords for this article

arthrogryposis multiplex congenita; dystonia; TOR1A; torsinA