Focal Facial Dermal Dysplasia 2, Brauer-Setleis Type

Description

The focal dermal dysplasias (FFDDs) are a group of related developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. FFFD2 is an autosomal dominant disorder characterized by bitemporal skin lesions with variable facial findings, including thin and puckered periorbital skin, distichiasis and/or absent eyelashes, upslanting palpebral fissures, a flat nasal bridge with a broad nasal tip, large lips, and redundant facial skin. FFDD3 (227260) is characterized by the same facial features as FFDD2, but the inheritance is autosomal recessive (summary by Slavotinek et al., 2013).

For a classification and a discussion of genetic heterogeneity of FFDD, see FFDD1 (136500).

Clinical Features

Ward and Moss (1994) suggested that the Setleis syndrome and type I focal facial dermal dysplasia (Brauer syndrome) 'are a single disorder.' They described a family in which the mother and 3 children had typical lesions on the temples and facial features, which they interpreted as similar to those in Setleis syndrome. The leonine facies described by Setleis et al. (1963) resulted from a combination of frontal bossing, redundant facial skin, periorbital puffiness, and flattened nasal bridge with a bulbous nasal tip.

Kaplan et al. (1995) presented evidence that the Setleis and Brauer forms of focal facial dermal dysplasia may be the same entity inherited in an autosomal dominant manner. They described a proband with bitemporal 'scars,' sparse lateral eyebrows, bulbous nose tip, thick lips, micrognathia, chin crease, imperforate anus and rectocutaneous fistula, bilateral megaureters, hypotonia, growth and developmental delay, and nonconsanguineous parents. His father had only bitemporal 'scarring,' bulbous nose tip, and hypertension.

Masuno et al. (1995) described a Japanese family in which a 9-month-old boy had typical Setleis syndrome; his father who had normal intelligence showed bitemporal focal dermal dysplasia but a normal face; and a paternal second cousin also had Setleis syndrome.

McGaughran and Aftimos (2002) reported Setleis syndrome in 3 patients, a Caucasian boy and a father and son of Pacific Island descent. In addition to bilateral temporal defects, the father and son both had linear markings on their mid-lower foreheads. The other boy had linear indentations parallel and just above the eyebrows. The 2 boys also had unruly hair, 1 with a double whorl. All 3 patients had developmental delay or learning difficulties.

Graul-Neumann et al. (2009) described the clinical features of 4 of 12 affected members from a large multigenerational German family with what the authors termed 'Brauer-Setleis syndrome.' All 4 had large bitemporal discolored dermal depressions ('forceps marks'), sparse lateral eyebrows, abnormal eyelashes, and dysplastic and low-set ears. Three had congenital horizontal nystagmus, which had hitherto only been reported in a single patient with FFDD.

Inheritance

Di Lernia et al. (1991) and Artlich et al. (1992) each described a family in which one of the parents of a patient with Setleis syndrome showed mild manifestations suggesting autosomal dominant inheritance.

Masuno et al. (1995) suggested that the pattern of inheritance in a Japanese family with Setleis syndrome was consistent with autosomal dominant transmission with variable expressivity and reduced penetrance.

Kaplan et al. (1995) suggested that the disorder they described with features of Brauer and Setleis syndromes was inherited in an autosomal dominant manner with variable expressivity.

Father-to-son transmission of Setleis syndrome in the family reported by McGaughran and Aftimos (2002) was consistent with autosomal dominant inheritance.

The transmission pattern of Brauer-Setleis syndrome in the families reported by Graul-Neumann et al. (2009) was consistent with autosomal dominant inheritance.