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Setleis syndrome in Mexican-Nahua sibs due to a homozygous TWIST2 frameshift mutation and partial expression in heterozygotes: review of the focal facial dermal dysplasias and subtype reclassification
  1. David E Cervantes-Barragán1,
  2. Camilo E Villarroel1,
  3. Alma Medrano-Hernández1,
  4. Carola Durán-McKinster2,
  5. Vanessa Bosch-Canto3,
  6. Victoria del-Castillo1,
  7. Irina Nazarenko4,
  8. Amy Yang4,
  9. Robert J Desnick4
  1. 1Department of Human Genetics, National Institute of Pediatrics of Mexico, Mexico City, Mexico
  2. 2Department of Dermatology, National Institute of Pediatrics of Mexico, Mexico City, Mexico
  3. 3Department of Ophthalmology, National Institute of Pediatrics of Mexico, Mexico City, Mexico
  4. 4Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA
  1. Correspondence to Dr Robert J Desnick, Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, Fifth Avenue at 100th Street, Box 1498, New York, NY 10029, USA; robert.desnick{at}


Background The focal facial dermal dysplasias (FFDDs) are a group of inherited disorders of facial development, characterised by bitemporal or preauricular scar-like defects, the former resembling ‘forceps marks’. Recently, different homozygous TWIST2 nonsense mutations were reported in unrelated Setleis syndrome (FFDD Type III) patients from consanguineous families, consistent with autosomal recessive inheritance. Mexican-Nahua sibs with facial and ophthalmologic features of FFDD type III were evaluated.

Methods Genomic DNAs were isolated for sequencing of the TWIST2 gene. The clinical features and inheritance of all previously reported FFDD patients were reviewed.

Results The affected sibs were homozygous for a novel TWIST2 frameshift mutation, c.168delC (p.S57AfsX45). Notably, both parents and two heterozygous sibs had distichiasis and partial absence of lower eyelashes. The FFDD subtypes were reclassified: the ‘Brauer-Setleis’ phenotype (autosomal dominant with variable expressivity) as FFDD type II; and patients with preauricular lesions as a new subtype, FFDD type IV.

Conclusions FFDD type III heterozygotes with TWIST2 mutations may have syndromic manifestations. Review of previous FFDD patients resulted in reclassification of the subtypes.

  • Setleis syndrome
  • focal facial dermal dysplasia
  • autosomal recessive
  • heterozygote manifestation
  • sternal skin tags
  • reclassification of the FFDDs
  • cytogenetics
  • genetics
  • genetics screening
  • cancer: CNS
  • cell biology
  • clinical genetics
  • diagnosis
  • neurology

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  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Ethics Committee of the National Institute of Pediatrics, Mexico City, Mexico, and the Institutional Review Board of the Mount Sinai School of Medicine.

  • Provenance and peer review Not commissioned; externally peer reviewed.