Familial focal facial dermal dysplasia

McGeoch, A. H.

doi:10.1001/archderm.107.4.591

Cited by 14 publications

(12 citation statements)

References 10 publications

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“…At 15 years old, he had a right inguinal hernia repair; his abdominal ultrasound and echocardiograph were normal. A biopsy taken from the bitemporal lesions revealed hypoplastic dermis along with an absence of subcutaneous fat, typical of that previously described in affected individuals (1, 11, 12). His neurological evaluation was within normal limits, and he graduated from high school with honors.…”

Section: Resultssupporting

confidence: 77%

Setleis syndrome: clinical, molecular and structural studies of the first TWIST2 missense mutation

et al. 2014

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Setleis syndrome is characterized by bitemporal scar-like lesions and other characteristic facial features. It results from recessive mutations that truncate critical functional domains in the basic helix-loop-helix (bHLH) transcription factor, TWIST2, which regulates expression of genes for facial development. To date, only four nonsense or small deletion mutations have been reported. In the current report, the clinical findings in a consanguineous Turkish family were characterized. Three affected siblings had the characteristic features of Setleis syndrome. Homozygosity for the first TWIST2 missense mutation, c.326T>C (p.Leu109Pro), was identified in the patients. In silico analyses predicted that the secondary structure of the mutant protein was sustained, but the empirical force field energy increased to an unfavorable level with the proline substitution (p.Leu109Pro). On a crystallographically generated dimer, p.Leu109 lies near the dimer interface, and the proline substitution is predicted to hinder dimer formation. Therefore, p.Leu109Pro-TWIST2 alters the three dimensional structure and is unable to dimerize, thereby hindering the binding of TWIST2 to its target genes involved in facial development.

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Section: Resultssupporting

confidence: 77%

Setleis syndrome: clinical, molecular and structural studies of the first TWIST2 missense mutation

et al. 2014

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“…These lesions typically are round, depressed areas that range from one to ten in number and up to one cm in diameter [Sybert, ]. However, these lesions may be larger, solid and single defects measuring up to six cm in diameter [McGeoch and Reed, ; Rudolph et al, ]. The atrophic skin normally lacks adnexal structures [Rudolph et al, ; Kowalski and Fenske, ].…”

Section: Discussionmentioning

confidence: 99%

“…The atrophic skin normally lacks adnexal structures [Rudolph et al, ; Kowalski and Fenske, ]. The subcutaneous fat is absent and skeletal muscle is attached to the epidermis, consistent with a mesodermal dysplasia (McGeoch and Reed, ; Setleis et al, ; Tukel et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…As noted above, both autosomal dominant and autosomal recessive inheritance have been reported in FFDD/SS patients [Jensen, ; McGeoch and Reed, ; Kowalski and Fenske, ; Graul‐Neumann et al, ; Tukel et al, ; Cervantes‐Barragán et al, ; Desnick and Lee, ]. Some individuals with the autosomal recessive form of FFDD have also been reported to have upper lid distichiasis and absent eyelashes of the lower lids [Jensen, ; Cervantes‐Barragán et al, ].…”

Section: Discussionmentioning

confidence: 99%

“…Until recently, the genes causing FFDD/SS were unknown. Multiple reports support an autosomal recessive inheritance in some families [Setleis et al, ; Marion et al, ; Clark et al, ; Frederick and Robb, ; Kowalski and Fenske, ; Slavotinek et al, ], while the inheritance in others is most consistent with an autosomal dominant mechanism [McGeoch and Reed, ; Di Lernia et al, ; Artlich et al, ; Ward and Moss, ; Masuno et al, ; Tsuda et al, ; McGaughran and Aftimos, ; Kent et al, ]. The first reported gene was published by Tukel et al [] who found homozygous nonsense mutations in TWIST2 , a basic helix‐loop‐helix ( bHLH ) transcription factor gene, as the cause of Setleis syndrome in consanguineous Puerto Rican and Arab kindreds.…”

Section: Introductionmentioning

confidence: 99%

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Chromosome 1p36.22p36.21 duplications/triplication causes Setleis syndrome (focal facial dermal dysplasia type III)

Weaver

Norby

Rosenfeld

et al. 2015

American J of Med Genetics Pt A

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Focal facial dermal dysplasias (FFDD) are characterized by congenital bitemporal or preauricular atrophic skin lesions, and either autosomal dominant or autosomal recessive inheritance. Setleis syndrome (SS), FFDD type III, is a severe form of FFDD with the ectodermal lesions plus other striking facial features. Autosomal recessive nonsense and frameshift mutations in TWIST2 have been found to cause SS in some but not all individuals. Here, we report on four unrelated individuals, one with an unclassified FFDD and the other three with classic SS. Chromosomal microarray analyses revealed unique copy number variants of 1p36 in two individuals with duplications at 1p36.22p36.21 and one with a triplication at 1p36.22p36.21. The fourth patient had normal chromosomes by microarray analysis. All four patients had normal TWIST2 exonic sequences. We propose that a dosage effect of one or more of the 30 genes in the 1.3 Mb 1p36.22p36.21 region of overlap is responsible for FFDD/SS manifestations in some individuals, and this mechanism would be inherited as an autosomal dominant trait. In patients with no duplication/triplication of the 1p36.22p36.21 region and no mutations in TWIST2, there are mutation(s) in one of the 30 genes in this region or mutations in other as yet unidentified genes at different locations that may affect the expressions of genes in this region or act independently to cause this developmental disease phenotype.

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