COFS type 3 in an Indian family with antenatally detected arthrogryposis

Am J Med Genet A. 2021 Feb;185(2):631-635. doi: 10.1002/ajmg.a.61979. Epub 2020 Nov 21.


Fetal akinesia and contractures can be caused by mutations in various genes that lead to overlapping phenotypes with contractures, rocker bottom feet, cerebellar hypoplasia, ventriculomegaly, growth retardation, pulmonary hypoplasia, cystic hygroma and cleft palate in various combinations. Cerebro-oculo-facio-skeletal (COFS) syndrome is a condition resulting from defects in DNA repair pathway, and genes involved include ERCC1 (COFS), ERCC2 (XPD), ERCC5(XPG), and ERCC6 (CSB). It is a severe disorder presenting in fetal or neonatal period with microcephaly, arthrogryposis, prominent nose, and kyphoscoliosis, and leads to early death in childhood. We report a baby with antenatally identified arthrogryposis in which the homozygous pathogenic variant in exon 8 was identified in ERCC5 gene, by targeted next generation sequencing. This was predicted to cause premature chain termination in the protein. ERCC5 gene is mainly implicated in xeroderma pigmentosum, sometimes in COFS syndrome.

Keywords: contractures; fetal akinesia; hydrocephalus; rocker bottom foot; ventriculomegaly.

Publication types

  • Case Reports

MeSH terms

  • Arthrogryposis / complications
  • Arthrogryposis / diagnosis
  • Arthrogryposis / genetics*
  • Arthrogryposis / pathology
  • Child
  • Cockayne Syndrome / complications
  • Cockayne Syndrome / diagnosis
  • Cockayne Syndrome / genetics*
  • Cockayne Syndrome / pathology
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Microcephaly / diagnosis
  • Microcephaly / genetics
  • Microcephaly / pathology
  • Nuclear Proteins / genetics*
  • Prenatal Diagnosis
  • Transcription Factors / genetics*
  • Xeroderma Pigmentosum / diagnosis
  • Xeroderma Pigmentosum / genetics
  • Xeroderma Pigmentosum / pathology


  • DNA excision repair protein ERCC-5
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors
  • Endonucleases

Supplementary concepts

  • Cerebrooculofacioskeletal Syndrome 1