Setleis syndrome is an extremely rare autosomal recessive disorder that belongs to a group of diseases known as ectodermal dysplasias. Ectodermal dysplasia syndromes are a heterogeneous group of disorders that share primary defects in the development of two or more tissues derived from ectoderm. These tissues are, primarily, the skin, hair, nails, eccrine glands, and teeth. Setleis syndrome is characterized by cutis aplasia or atrophic skin at the temples, which is said to resemble forceps marks. There may also be a coarse facial appearance, anomalies of the eyelashes and eyebrows, and periorbital puffiness. The mouth has a typical appearance with large lips, inverted "V" contour, and down turned overly defined corners.
Setleis syndrome results from mutations in the TWIST2 gene, which encodes a transcription factor that functions as an important regulator of gene expression during the differentiation of mesenchymal stem cells.