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Focal facial dermal dysplasia type I(FFDD1)

MedGen UID:
1718224
Concept ID:
C5235196
Disease or Syndrome
Synonyms: Bitemporal aplasia cutis congenita; Brauer syndrome; FFDD, type 1; Focal facial dermal dysplasia 1, Brauer type; Hereditary symmetrical aplastic nevi of temples
SNOMED CT: Focal facial dermal dysplasia type I (789157007); Brauer syndrome (789157007); Focal facial dermal dysplasia 1 Brauer type (789157007); Bitemporal aplasia cutis congenita (789157007); FFDD type 1 - focal facial dermal dysplasia type 1 (789157007)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Monarch Initiative: MONDO:0007627
OMIM®: 136500
Orphanet: ORPHA79133

Definition

The focal dermal dysplasias (FFDDs) are a group of related developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. Cervantes-Barragan et al. (2011) proposed a classification of FFDD in which there are 4 subtypes. FFDD1 (Brauer syndrome) is characterized by temporal skin depressions that resemble 'forceps marks.' Other facial anomalies, comprising sparse lateral eyebrows, distichiasis, and a flattened nasal tip, are usually mild. Inheritance is autosomal dominant. FFFD2 (Brauer-Setleis syndrome; 614973) is 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. Inheritance is autosomal dominant. FFDD3 (Setleis syndrome; 227260) is characterized by the same facial features as FFDD2, but the inheritance is autosomal recessive. FFDD4 (614974) is characterized by isolated, preauricular skin lesions with autosomal dominant or recessive inheritance (summary by Slavotinek et al., 2013). Genetic Heterogeneity of Focal Facial Dermal Dysplasia FFDD3 (227260) is caused by mutation in the TWIST2 gene (607556) on chromosome 2q37. FFDD4 (614974) is caused by mutation in the CYP26C1 gene on chromosome 10q23. [from OMIM]

Clinical features

From HPO
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Sparse lateral eyebrow
MedGen UID:
387768
Concept ID:
C1857206
Finding
Decreased density/number and/or decreased diameter of lateral eyebrow hairs.
Bitemporal forceps marks
MedGen UID:
893154
Concept ID:
C4023409
Finding
Bilateral temporal scarlike defects, which are said to resemble forceps marks.
Distichiasis
MedGen UID:
98074
Concept ID:
C0423848
Anatomical Abnormality
Double rows of eyelashes.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFocal facial dermal dysplasia type I

Recent clinical studies

Etiology

Oh RY, Chun K, Kowalski PE, Chitayat D
Am J Med Genet A 2023 Jun;191(6):1607-1613. Epub 2023 Mar 21 doi: 10.1002/ajmg.a.63175. PMID: 36942595
Lee BH, Morice-Picard F, Boralevi F, Chen B, Desnick RJ
J Hum Genet 2018 Mar;63(3):257-261. Epub 2017 Dec 20 doi: 10.1038/s10038-017-0375-x. PMID: 29263414
Giordano L, Desnick RJ, Molinaro A, Uliana V, Forzano F, Edelmann L, Nazarenko I, Pinelli L, Accorsi P, Faravelli F
Pediatr Neurol 2014 Apr;50(4):389-91. Epub 2013 Dec 14 doi: 10.1016/j.pediatrneurol.2013.12.009. PMID: 24486222
Tukel T, Šošić D, Al-Gazali LI, Erazo M, Casasnovas J, Franco HL, Richardson JA, Olson EN, Cadilla CL, Desnick RJ
Am J Hum Genet 2010 Aug 13;87(2):289-96. doi: 10.1016/j.ajhg.2010.07.009. PMID: 20691403Free PMC Article
Kowalski DC, Fenske NA
J Am Acad Dermatol 1992 Oct;27(4):575-82. doi: 10.1016/0190-9622(92)70225-5. PMID: 1401310

Diagnosis

Oh RY, Chun K, Kowalski PE, Chitayat D
Am J Med Genet A 2023 Jun;191(6):1607-1613. Epub 2023 Mar 21 doi: 10.1002/ajmg.a.63175. PMID: 36942595
Mehrtens SH, Shankar S
Pediatr Dermatol 2019 Jan;36(1):e58-e59. Epub 2018 Dec 18 doi: 10.1111/pde.13730. PMID: 30561078
Lee BH, Morice-Picard F, Boralevi F, Chen B, Desnick RJ
J Hum Genet 2018 Mar;63(3):257-261. Epub 2017 Dec 20 doi: 10.1038/s10038-017-0375-x. PMID: 29263414
Coughlin CC, Dunbar SW, Bayliss SJ, Berk DR
Pediatr Dermatol 2013 Nov-Dec;30(6):e259-60. Epub 2012 Oct 29 doi: 10.1111/pde.12009. PMID: 23106109
Tukel T, Šošić D, Al-Gazali LI, Erazo M, Casasnovas J, Franco HL, Richardson JA, Olson EN, Cadilla CL, Desnick RJ
Am J Hum Genet 2010 Aug 13;87(2):289-96. doi: 10.1016/j.ajhg.2010.07.009. PMID: 20691403Free PMC Article

Prognosis

Lee BH, Morice-Picard F, Boralevi F, Chen B, Desnick RJ
J Hum Genet 2018 Mar;63(3):257-261. Epub 2017 Dec 20 doi: 10.1038/s10038-017-0375-x. PMID: 29263414
Rosti RO, Uyguner ZO, Nazarenko I, Bekerecioglu M, Cadilla CL, Ozgur H, Lee BH, Aggarwal AK, Pehlivan S, Desnick RJ
Clin Genet 2015 Nov;88(5):489-493. Epub 2014 Dec 11 doi: 10.1111/cge.12539. PMID: 25410422Free PMC Article
Slavotinek AM, Mehrotra P, Nazarenko I, Tang PL, Lao R, Cameron D, Li B, Chu C, Chou C, Marqueling AL, Yahyavi M, Cordoro K, Frieden I, Glaser T, Prescott T, Morren MA, Devriendt K, Kwok PY, Petkovich M, Desnick RJ
Hum Mol Genet 2013 Feb 15;22(4):696-703. Epub 2012 Nov 16 doi: 10.1093/hmg/dds477. PMID: 23161670Free PMC Article

Clinical prediction guides

Lee BH, Morice-Picard F, Boralevi F, Chen B, Desnick RJ
J Hum Genet 2018 Mar;63(3):257-261. Epub 2017 Dec 20 doi: 10.1038/s10038-017-0375-x. PMID: 29263414
Rosti RO, Uyguner ZO, Nazarenko I, Bekerecioglu M, Cadilla CL, Ozgur H, Lee BH, Aggarwal AK, Pehlivan S, Desnick RJ
Clin Genet 2015 Nov;88(5):489-493. Epub 2014 Dec 11 doi: 10.1111/cge.12539. PMID: 25410422Free PMC Article
Slavotinek AM, Mehrotra P, Nazarenko I, Tang PL, Lao R, Cameron D, Li B, Chu C, Chou C, Marqueling AL, Yahyavi M, Cordoro K, Frieden I, Glaser T, Prescott T, Morren MA, Devriendt K, Kwok PY, Petkovich M, Desnick RJ
Hum Mol Genet 2013 Feb 15;22(4):696-703. Epub 2012 Nov 16 doi: 10.1093/hmg/dds477. PMID: 23161670Free PMC Article

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