Ablepharon macrostomia syndrome: A distinct genetic entity clinically related to the group of FRAS-FREM complex disorders

Am J Med Genet A. 2013 Dec;161A(12):3012-7. doi: 10.1002/ajmg.a.36119. Epub 2013 Sep 24.


Ablepharon macrostomia syndrome (AMS; OMIM 200110) is an extremely rare congenital malformation syndrome. It overlaps clinically with Fraser syndrome (FS; OMIM 219000), which is known to be caused by mutations in either FRAS1, FREM2, or GRIP1, encoding components of a protein complex that plays a role in epidermal-dermal interactions during morphogenetic processes. We explored the hypothesis that AMS might be either allelic to FS or caused by mutations in other genes encoding known FRAS1 interacting partners. No mutation in either of these genes was found in a cohort of 11 patients with AMS from 10 unrelated families. These findings demonstrate that AMS is genetically distinct from FS. It is proposed that it constitutes a separate entity within the group of FRAS-FREM complex disorders.

Keywords: Fraser syndrome; ablepharon macrostomia syndrome; cryptophthalmos; genitourinary anomalies; syndactyly.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Abnormalities, Multiple / etiology
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / physiopathology*
  • Carrier Proteins / genetics
  • Extracellular Matrix Proteins / genetics
  • Eye Abnormalities / etiology
  • Eye Abnormalities / genetics*
  • Eye Abnormalities / physiopathology*
  • Female
  • Fraser Syndrome / genetics*
  • Fraser Syndrome / physiopathology
  • Humans
  • Macrostomia / etiology
  • Macrostomia / genetics*
  • Macrostomia / physiopathology*
  • Male
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Phenotype


  • Carrier Proteins
  • Extracellular Matrix Proteins
  • FRAS1 protein, human
  • FREM2 protein, human
  • GRIP1 protein, human
  • Nerve Tissue Proteins

Supplementary concepts

  • Ablepharon macrostomia syndrome