Ablepharon macrostomia syndrome

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Ablepharon macrostomia syndrome
Other namesAMS
Autosomal dominant - en.svg
Ablepharon macrostomia syndrome has an autosomal dominant pattern of inheritance

Ablepharon macrostomia syndrome (AMS) is an extremely rare autosomal dominant genetic disorder characterized by malformations of the skull, skin, fingers and genitals.[1] Affected individuals may also have malformations of the nipples and abdominal wall.

Younger individuals might experience language difficulties, and in some instances intellectual disabilities are known.[2]

AMS is phenotypically similar to Barber-Say syndrome, which also demonstrates autosomal dominant inheritance.


  • Absent/short eyelids
  • Absent eyebrows
  • Absent eyelashes
  • External ear abnormalities
  • Alopecia


AMS is inherited in an autosomal dominant manner.[3][4] Like Barber-Say syndrome, AMS is caused by mutations in the TWIST2 gene that affect a highly conserved residue of TWIST2 (twist-related protein 2). TWIST2 is a basic helix-loop-helix transcription factor that binds to E-box DNA motifs (5'-CANNTG-3') as a heterodimer and inhibits transcriptional activation.[5] Because TWIST2 mediates mesenchymal stem cell differentiation[6] and prevents premature or ectopic osteoblast differentiation,[7] mutations in TWIST2 that disrupt these functions by altering DNA-binding activity could explain many of the phenotypes of AMS.[3]


Ablepharon macrostomia syndrome can be diagnosed at birth by identification of characteristic physical findings, clinical evaluation, and specialized imaging techniques such as CT scans.[8]


Treatment usually involves plastic and reconstructive surgery. Surgery may be needed to correct undescended testes or hernias.


  1. ^ Ferraz VE, Melo DG, Hansing SE, Cruz AA, Pina-Neto JM (October 2000). "Ablepharon-macrostomia syndrome: first report of familial occurrence". Am. J. Med. Genet. 94 (4): 281–3. doi:10.1002/1096-8628(20001002)94:4<281::AID-AJMG3>3.0.CO;2-S. PMID 11038439.
  2. ^ "Ablepharon macrostomia syndrome". Retrieved 2009-11-24.
  3. ^ a b Marchegiani, Shannon; Davis, Taylor; Tessadori, Federico; van Haaften, Gijs; Brancati, Francesco; Hoischen, Alexander; Huang, Haigen; Valkanas, Elise; Pusey, Barbara (2015-07-02). "Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes". The American Journal of Human Genetics. 97 (1): 99–110. doi:10.1016/j.ajhg.2015.05.017. ISSN 0002-9297. PMC 4572501. PMID 26119818.
  4. ^ Rohena, Luis; Kuehn, Devon; Marchegiani, Shannon; Higginson, Jason D. (2011). "Evidence for autosomal dominant inheritance of ablepharon-macrostomia syndrome". American Journal of Medical Genetics. Part A. 155A (4): 850–854. doi:10.1002/ajmg.a.33900. ISSN 1552-4833. PMID 21595001.
  5. ^ "TWIST2 - Twist-related protein 2 - Homo sapiens (Human) - TWIST2 gene & protein". Retrieved 2019-01-25.
  6. ^ Isenmann, Sandra; Arthur, Agnieszka; Zannettino, Andrew CW; Turner, Jenna L.; Shi, Songtao; Glackin, Carlotta A.; Gronthos, Stan (2009). "TWIST Family of Basic Helix-Loop-Helix Transcription Factors Mediate Human Mesenchymal Stem Cell Growth and Commitment". Stem Cells. 27 (10): 2457–2468. doi:10.1002/stem.181. ISSN 1066-5099. PMID 19609939.
  7. ^ Lee, M. S; Lowe, G; Flanagan, S; Kuchler, K; Glackin, C. A (2000-11-01). "Human dermo-1 has attributes similar to twist in early bone development". Bone. 27 (5): 591–602. doi:10.1016/S8756-3282(00)00380-X. ISSN 8756-3282.
  8. ^ "Ablepharon-Macrostomia Syndrome". NORD (National Organization for Rare Disorders). Retrieved 2019-04-19.

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