Cerebrofaciothoracic dysplasia: Four new patients with a recurrent TMCO1 pathogenic variant

Deciphering Developmental Disorders (DDD) Study, Thabo Michael Yates, Oon Hui Ng, Amaka C. Offiah, Josh Willoughby, Jonathan N. Berg, Diana S. Johnson (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
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Biallelic loss of function variants in the TMCO1 gene have been previously demonstrated to result in cerebrofaciothoracic dysplasia (CFTD; MIM #213980). The phenotype of this condition includes severe intellectual disability, as well as distinctive craniofacial features, including brachycephaly, synophrys, arched eyebrows, “cupid's bow” upper lip, and microdontia. In addition, nonspecific skeletal anomalies are common, including bifid ribs, scoliosis, and spinal fusion. Only 19 molecularly confirmed patients have been previously described. Here, we present four patients with CFTD, including three brothers from a Pakistani background and an additional unrelated white Scottish patient. All share the characteristic craniofacial appearance, with severe intellectual disability and skeletal abnormalities. We further define the phenotype with comparison to the published literature, and present images to define the dysmorphic features in a previously unreported ethnic group. All of our patient series are homozygous for the same c.292_293del (p.Ser98*) TMCO1 pathogenic variant, which has been previously reported only in an isolated Amish population. Thus we provide evidence that CFTD may be more common than previously thought. The patients presented here further delineate the phenotypic spectrum of CFTD and provide evidence for a recurrent pathogenic variant in TMCO1.

Original languageEnglish
Pages (from-to)43-49
Number of pages7
JournalAmerican Journal of Medical Genetics Part A
Issue number1
Early online date17 Dec 2018
Publication statusPublished - Jan 2019


  • cerebrofaciothoracic dysplasia
  • intellectual disability
  • TMCO1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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