Ablepharon Macrostomia Syndrome

Ablepharon Macrostomia Syndrome (AMS) is a syndrome that may or may not be considered intersex, depending on who you ask. Some may consider this syndrome to be a cause for intersex traits, rather than an intersex trait in of itself. This syndrome is often found to overlap or be similar to Fraser Syndrome, and can effect both CTM and CTF individuals alike.

Symptoms exclusively found within CTF individuals with AMS include labial hypoplasia and absent breasts, while a symptom exclusively found in CTM individuals with AMS is penile agenesis (an underdeveloped or absent penis.)

Symptoms that can be found in CTM and CTF individuals with AMS include ambiguous genitalia, absent or small nipples, loose and/or thin skin, wrinkled skin, club feet, fused toes, shortened hands, absent or underdeveloped eyelids, absent eyebrows, absent eyelashes, fine hair, small ears, nasal abnormalities, large teeth, lip abnormalities, and underdeveloped cheekbones and/or jawbones. They may also be blind and/or deaf, or have other sight and/or hearing impairments.

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 specific types of DNA. Mutations in the TWIST2 gene alter DNA-binding activity, and could explain many of the phenotypes of AMS.

This variation is similar to Barber Say Syndrome and Facial Ectodermal Dysplasia.