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

Sarlkaya E., Özçelik F., GÜL ŞİRAZ Ü., HATİPOĞLU N., GÜNEŞ T., DÜNDAR M.

Journal of Pediatric Endocrinology and Metabolism, vol.35, no.6, pp.845-850, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 35 Issue: 6
  • Publication Date: 2022
  • Doi Number: 10.1515/jpem-2021-0766
  • Journal Name: Journal of Pediatric Endocrinology and Metabolism
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, MEDLINE
  • Page Numbers: pp.845-850
  • Keywords: arthrogryposis multiplex congenita, dystonia, TOR1A, torsinA, CLASSIFICATION, TORSINA
  • Kayseri University Affiliated: No


© 2022 Walter de Gruyter GmbH, Berlin/Boston.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.