Information on the following diseases can be found in the Related Disorders section of this report:

• Focal facial dermal dysplasia type I (Brauer syndrome)
• Ectodermal dysplasias (general)

Setleis syndrome, an extremely rare inherited disorder, belongs to a group of diseases known as ectodermal dysplasias that typically affect the hair, teeth, nails, and/or skin. Setleis syndrome is characterized by distinctive abnormalities of the facial area. The range and severity of symptoms may vary from case to case.

Infants with Setleis syndrome have multiple, scar-like, circular depressions on both temples (bitemporal) that strongly resemble the marks made during a forceps delivery. According to some researchers, these "forceps marks" may represent aplasia cutis congenita, a rare condition characterized by failure of development of skin and hair in certain areas (localized), most often on the scalp; absence of certain structures just below the skin's surface (e.g., sweat glands); and/or the development of scar tissue or a thin membrane over the affected area. For example, in some infants with Setleis syndrome, the outermost layer of skin (epidermis) in the temple area may be abnormally thin and the hair follicles, sweat glands, and sebaceous glands normally located within the thick inner layer of skin (dermis) may be absent. The sebaceous glands produce a thick, oily substance (sebum) that helps the skin retain body heat and prevent the evaporation of sweat.

In addition, in most infants with Setleis syndrome the skin around the eyes (periorbital) is puffy and wrinkled, giving them an aged appearance. In some cases, affected infants may also have an abnormally prominent forehead (frontal bossing) and eyebrows that grow upward and outward, but have sparse side growth. In some cases, as a result of characteristic facial features, affected infants may have a coarse or "leonine" (lion-like) facial appearance.

In most cases, infants with Setleis syndrome also have abnormalities of the eyelashes such as absence of the eyelashes on both the upper and lower lids or multiple rows of eyelashes on the upper lids (distichiasis) and none on the lower lids (astichiasis). In some cases, abnormalities of the eyelashes may lead to redness, inflammation, and/or swelling of the eyelids with scaly skin forming at the ends of the eyelids and flakes of discharge collecting in the corners or on the lashes. Eventually, infections may occur at the base of the lashes (blepharitis), and the eyes themselves may become red.

In many cases, affected infants may have other abnormalities affecting the eyes. For example, the transparent, thin membrane that protects and helps lubricate the eyelids and whites of the eyes (conjunctiva) may become inflamed (conjunctivitis). In some cases, infants with Setleis syndrome may have downward slanting eyelid slits (palpebral fissures), excess folds of skin on either side of the nose that cover the eyes' inner corners (epicanthal folds), or, in rare cases, crossed eyes (strabismus).

Infants with Setleis syndrome may also have additional abnormalities of the facial area. The bridge of the nose may appear flat, while the tip of the nose may appear abnormally rounded (bulbous). In some cases, the wall that divides the two chambers of the nose (nasal septum) may extend below the nostrils (alae nasae). In most cases, infants have a downturned mouth, an abnormally prominent upper lip, and/or unusually thick lips. In some cases, abnormal thickness of the lips may be due, in part, to increased mobility of the skin. In addition, affected children may have loose, excessive (redundant) facial skin, and the skin of the nose and the chin may appear abnormally flexible or "rubbery." Some affected individuals may also have small, malformed ears and/or an abnormal groove or furrow in the chin (cleft chin). Facial abnormalities may become less pronounced as affected children age.

In addition, many individuals with Setleis syndrome have distinctive abnormalities involving hair growth. Affected individuals may have thin scalp hair, abnormal bald patches on the scalp (alopecia), and/or a low frontal hairline.

In a few cases, children with Setleis syndrome have additional abnormalities. For example, they may have patches of skin that appear darker or lighter in various areas of the body (hyper- or hypopigmentation), such as light brown "coffee-colored" discolorations (cafe-au-lait spots) or patches of skin that lack color (vitiligo). In some cases, affected individuals have abnormal creases or lines on the palms of the hands (palmar creases).

Some researchers believe that Setleis syndrome is a form of focal facial dermal dysplasia (FFDD), which has been described as a group of rare inherited disorders that may be characterized by the presence of scar-like depressions on the temples at birth, potentially in association with additional facial abnormalities. For more information, please see the "Related Disorders" section of this report.

In most cases, Setleis syndrome is thought to be inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

Some cases of Setleis syndrome have had parents who were related by blood (consanguineous). All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

A number of cases of Setleis syndrome have been reported in which a parent of an affected individual as demonstrated mild manifestations of the disorder. As a result, some researchers suspect that, in some cases, Setleis syndrome may be inherited as an autosomal dominant trait with great differences in manifestation from case to case (variable expression) and may not be manifested in all those who inherit the gene (incomplete penetrance).

In cases of possible autosomal dominant inheritance, researchers have proposed that Setleis syndrome may be the same disorder as focal facial dermal dysplasia type I, a rare disorder that is inherited as an autosomal dominant trait with variable expressivity. For more information, please see the "Related Disorders" section of this report.
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Setleis syndrome is an extremely rare inherited disorder that, in theory, affects males and females in equal numbers. Approximately 20 cases have been reported in the medical literature. The majority of these cases have occurred in individuals from Puerto Rico.
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Symptoms of the following disorders can be similar to those of Setleis syndrome. Comparisons may be useful for a differential diagnosis:

Focal facial dermal dysplasia (FFDD) type I, also known as Brauer syndrome, is a rare inherited disorder characterized by scar-like depressions on the temples, similar to those that may be caused by forceps when used during delivery. In addition, affected individuals may have wrinkled, puffy skin in the temple area and teardrop-shaped (guttate) lesions on the chin and middle of the forehead. Focal facial dermal dysplasia type I is thought to be inherited as an autosomal dominant genetic trait with variable expressivity. There is some confusion in the medical literature concerning the relationship of focal facial dermal dysplasia type I and Setleis syndrome. While some researchers believe that FFDD Type I and Setleis syndrome are different forms of focal facial dermal dysplasia, others suspect that they represent the same disease entity.

Ectodermal dysplasias (EDs) are a group of rare inherited multisystem disorders that typically affect the hair, teeth, nails, and/or skin. Several other ectodermal dysplasia disorders may be characterized by sparse or absent hair, absence or improper functioning of sweat glands, skin abnormalities, malformations of the nose, and/or other abnormalities similar to those associated with Setleis syndrome. (For more information on these disorders, choose "Ectodermal Dysplasias" or the exact disease name in question as your search term in the Rare Disease Database.)

Diagnosis
Setleis syndrome is usually diagnosed shortly after birth based upon a thorough clinical evaluation and identification of characteristic features, such as distinctive scar-like, circular depressions on both temples; an aged and/or "leonine" facial appearance; and characteristic abnormalities of the eyelashes, eyebrows, and eyelids. It is possible that microscopic examination of small samples of skin tissue (biopsy) from the temples may reveal abnormal thinning of the outer layer of the skin (epidermis) and absence of certain specialized structures normally located within the inner layer of the skin (e.g., sweat glands, sebaceous glands, hair follicles).

Treatment
Treatment is directed toward the specific symptoms that are apparent in each individual. In some cases, removal of excess eyelashes (epilation) that are growing toward the eyes may help reduce eye irritation. Blepharitis is treated symptomatically. Because facial abnormalities tend to lessen as an affected child ages, surgery may be postponed to monitor facial development. However, in some cases, corrective surgery may eventually be performed. Other treatment for this disorder is symptomatic and supportive.

Genetic counseling is of benefit for affected individuals and their families. Family members of affected individuals should also receive regular clinical evaluations to detect any symptoms and physical characteristics that may be associated with Setleis syndrome.

Researchers at the University of Puerto Rico were studying the molecular genetics of Setleis syndrome. For more information, contact:

Carmen L. Cadilla, Professor
University of Puerto Rico
School of Medicine
Dept. of Biochemistry
P.O. Box 365067
San Juan, PR 00936-5067
Email: c_cadilla@rcmaca.upr.clu.edu

Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 227260; 8/12/96. Available at: http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?227260

Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 136500; 11/2/95. Available at: http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?136500

TEXTBOOKS
Buyce ML, ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:598-99.

Gorlin RJ, et al., eds. Syndromes of the Head and Neck, 3rd ed. New York, NY: Oxford University Press; 1990:514.

Champion RH, et al., eds. Textbook of Dermatology. 5th ed. Cambridge, MA: Blackwell Scientific Publications; 1992:358.

JOURNAL ARTICLES
McGaughran J, Aftimos S, et al. Setleis syndrome: three new cases and a review of the literature. Am J Med Genet. 2002;111:376-80.

Tanabe A. Treatment of Setleis syndrome. Case report. Scand J Plast Reconstr Surg Hand Surg. 2001;35:107-11.

al-Gazali LI, et al. Setleis syndrome: autosomal recessive or autosomal dominant inheritance? Clin Dysmorphol. 1996;5:249-53.

Masuno M, et al. Autosomal dominant inheritance in Setleis syndrome. Am J Med Genet. 1995;57:57-60.

Ward KA, et al. Evidence for genetic homogeneity of Setleis' syndrome and focal facial dermal dysplasia. Br J Dermatol. 1994;130:645-49.

Artlich A, et al. Setleis (bitemporal 'forceps marks') syndrome in a German family: evidence for autosomal dominant inheritance. Clin Dysmorphol. 1992;1:157-60.

Kowalski DC, et al. The focal facial dermal dysplasias: report of a kindred and a proposed new classification. J Am Acad Dermatol. 1992;27:575-82.

Clark RD, et al. Expanded phenotype and ethnicity in setleis syndrome. Am J Med Genet. 1989;34:354-57.

Marlon RW, et al. Autosomal recessive inheritance in the Setleis bitemporal 'forceps marks' syndrome. Am J Dis Child. 1987;141:895-97.

Setleis H, et al. Congenital ectodermal dysplasia of the face. Pediatrics. 1963;32:540-48.