Ablepharon macrostomia syndrome
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|Ablepharon macrostomia syndrome|
|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. Affected individuals may also have malformations of the nipples and abdominal wall.
AMS is phenotypically similar to Barber-Say syndrome, which also demonstrates autosomal dominant inheritance.
- Absent/short eyelids
- Absent eyebrows
- Absent eyelashes
- External ear abnormalities
AMS is inherited in an autosomal dominant manner. 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. Because TWIST2 mediates mesenchymal stem cell differentiation and prevents premature or ectopic osteoblast differentiation, mutations in TWIST2 that disrupt these functions by altering DNA-binding activity could explain many of the phenotypes of AMS.
Ablepharon macrostomia syndrome can be diagnosed at birth by identification of characteristic physical findings, clinical evaluation, and specialized imaging techniques such as CT scans.
Treatment usually involves plastic and reconstructive surgery. Surgery may be needed to correct undescended testes or hernias.
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