title: 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.
abstract: 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.
authors.affiliation: Department of Human Genetics, National Institute of Pediatrics of Mexico, Mexico City, Mexico.
authors.forename: David E
authors.initials: DE
authors.lastname: Cervantes-Barragán
authors.forename: Camilo E
authors.initials: CE
authors.lastname: Villarroel
authors.forename: Alma
authors.initials: A
authors.lastname: Medrano-Hernández
authors.forename: Carola
authors.initials: C
authors.lastname: Durán-McKinster
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bosch-Canto
authors.forename: Victoria
authors.initials: V
authors.lastname: Del-Castillo
authors.forename: Irina
authors.initials: I
authors.lastname: Nazarenko
authors.forename: Amy
authors.initials: A
authors.lastname: Yang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Desnick
mesh_terms: D002648:Child; D004476:Ectodermal Dysplasia; D005140:Eyelashes / Q000473:pathology; D005145:Face / Q000473:pathology; D005260:Female; D005489:Focal Dermal Hypoplasia / Q000235:genetics* / Q000473:pathology; D000090303:Focal Facial Dermal Dysplasias; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D007198:Indians, North American; D007223:Infant; D008297:Male; D008800:Mexico; D010375:Pedigree; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*; D035781:Siblings; D012871:Skin Diseases / Q000235:genetics* / Q000473:pathology; D051879:Twist-Related Protein 1 / Q000235:genetics*
chemical_list: D012097:Repressor Proteins; C486274:TWIST2 protein, human; D051879:Twist-Related Protein 1