The main clinical sign of Setleis syndrome (also known as focal facial dermal dysplasia type 3) is the appearance of bitemporal atrophic and scar-like lesions on the skin that resemble forceps marks [1] [2]. The term "forceps marks" is used due to the striking similarity with the lesions encountered after the use of forceps for assisted vaginal delivery. These lesions are characteristic of all focal facial dermal dysplasias (FFDDs), which is why additional features must be used to discern between the different types of dysplasias. Facial changes are typical for FFDD type 3, and most commonly identified abnormalities are: absence of eyelashes on both lids, leonine-like facies, multiple rows of eyelashes on the upper lids (termed distichiasis), sparse and slanted eyebrows, a flattened nasal bridge, a bulbous nose, clefting of the chin, absent Meibomian glands, wrinkled facial skin, and a low frontal hairline [1] [2] [3]. In addition, some patients may present with periorbital puffiness and a large and prominent upper lip [4]. Apart from facial and skin symptoms, some reports suggest that infants may suffer from developmental delay [4]. Setleis syndrome seems to affect all ethnic groups [1], but consanguineous marriages seem to be a significant risk factor, presumably due to autosomal dominant and recessive modes of inheritance [2] [5].

• Sparse to No Eyebrows

  Facial changes are typical for FFDD type 3, and most commonly identified abnormalities are: absence of eyelashes on both lids, leonine-like facies, multiple rows of eyelashes on the upper lids (termed distichiasis), sparse and slanted eyebrows, a flattened [symptoma.com]

• Facial Skin Lesion

  Further, Brauer syndrome ( 136500 ) (focal facial dermal dysplasia or FFDD type I) is clinically somewhat similar to Setleis syndrome with respect to the distribution and nature of facial skin lesions and it has been suggested that the two disorders may [disorders.eyes.arizona.edu]

• Periorbital Fullness

  Setleis syndrome is characterized by an aged, leonine facial appearance, puckered skin around the eyes with periorbital fullness, and absent or multiple rows of eyelashes. Flat nasal bridge, bulbous nasal tip, and big lips. [accessanesthesiology.mhmedical.com]

  There was periorbital fullness, the nasal bridgewas shallow, and his nose was thin with a bulbous tip(Fig. 2). He had multiple rows of eyelashes on the superiorlids and no lashes on the lower lids. [docslide.com.br]

• Bulbous Nose

  nose, clefting of the chin, absent Meibomian glands, wrinkled facial skin, and a low frontal hairline. [symptoma.com]

  Barber-Say syndrome (BBRSAY) [MIM:209885]: A rare ectodermal dysplasia characterized by ectropion, macrostomia, ear abnormalities, broad nasal bridge, bulbous nose, redundant skin, hypertrichosis, dental abnormalities, and variable other features. [genecards.org]

• Coarse Face

  Setleis syndrome, an autosomal recessive disorder characterized by "coarse" face, temporal cutis aplasia, double upper eyelashes, absent lower eyelashes, chronic conjunctivitis, and prominent thick lips, was reported previously in 8 Puerto Rican children [ncbi.nlm.nih.gov]

  Setleis syndrome, an autosomal recessive dis- order characterized by coarse face, tempo- ral cutis aplasia, double upper eyelashes, ab- sent lower eyelashes, chronic conjunctivitis, and prominent thick lips, was reported previ- ously in 8 Puerto Rican [documents.tips]

• Beak Nose

  Fig 1 (Top) Facial features ofSetleis syndrome in reported siblings: 1) Absent lateral portion of eyebrows, 2) bitemporal scarred, erythematotis skin resembling forceps scars, 3) redundant facial and periorbital skin, 4) "parrot-beak" nose, and 5) thickened [healio.com]

• Beaked Nose

  Fig 1 (Top) Facial features ofSetleis syndrome in reported siblings: 1) Absent lateral portion of eyebrows, 2) bitemporal scarred, erythematotis skin resembling forceps scars, 3) redundant facial and periorbital skin, 4) "parrot-beak" nose, and 5) thickened [healio.com]

• Facial Scar

  There is limited experience with plastic surgery for the facial scar-like lesions.PrognosisAffected individuals have a normal intelligence and life span.Visit the Orphanet disease page for more resources. [malacards.org]

Although Setleis syndrome is a very rare disease, the two most important steps in the diagnostic workup are a thorough physical examination and a detailed patient history, as diagnostic criteria focus solely on findings obtained during these procedures. Clinical features may be evident as early as birth, which is why temporal skin lesions should be easily observed in neonates and infants, together with additional facial deformities, although the diagnosis can be made as late as adolescence [2]. When an initial diagnosis is made, a thorough family history is necessary in order to confirm the presence of similar signs and symptoms in close family members or siblings. In some cases, a biopsy of the affected skin in the temporal region may be performed, which will show hypoplasia of the dermis and its inner structures (eg. hair follicles and sweat glands) or absence of subcutaneous adipose tissue [1] [2]. If strong suspicion exists, genetic testing should be advised. Mutations of TWIST2 on chromosome 2, a transcription factor that exhibits an important role in the embryologic development of bones and the dermis, seems to be responsible for the development of Setleis syndrome, and its evaluation is recommended in workup [1] [2].

1. Tukel T, Šošić D, Al-Gazali LI, et al. Homozygous Nonsense Mutations in TWIST2 Cause Setleis Syndrome. Am J Hum Genet. 2010;87(2):289-296.
2. Rosti RO, Uyguner ZO, Nazarenko I, et al. Setleis syndrome: Clinical, molecular and structural studies of the first TWIST2 missense mutation. Clin Genet. 2015;88(5):489-493.
3. Franco HL, Casasnovas JJ, Leon RG, et al. Nonsense mutations of the bHLH transcription factor TWIST2 found in Setleis Syndrome patients cause dysregulation of periostin. Int J Biochem Cell Biol. 2011;43(10):1523-1531.
4. McGaughran J, Aftimos S. Setleis syndrome: three new cases and a review of the literature. Am J Med Genet. 2002;111(4):376-380.
5. Slavotinek AM, Mehrotra P, Nazarenko I, et al. Focal facial dermal dysplasia, type IV, is caused by mutations in CYP26C1. Hum Mol Genet. 2013;22(4):696-703.