FFDD3
MCID: FCL045
MIFTS: 32

Focal Facial Dermal Dysplasia 3, Setleis Type (FFDD3)

Categories: Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Focal Facial Dermal Dysplasia 3, Setleis Type

MalaCards integrated aliases for Focal Facial Dermal Dysplasia 3, Setleis Type:

Name: Focal Facial Dermal Dysplasia 3, Setleis Type 56 58 73 13
Setleis Syndrome 56 74 52 58 73
Bitemporal Forceps Marks Syndrome 56 52 73
Facial Ectodermal Dysplasia 56 52 73
Ffdd3 56 58 73
Focal Facial Dermal Dysplasia Type Iii 58 73
Ffdd Type Iii 58 73
Focal Facial Dermal Dysplasia, Type Ii, Formerly 56
Dysplasia, Dermal, Focal Facial, Type 3 39
Congenital Ectodermal Dysplasia of Face 71
Focal Facial Dermal Dysplasia Type Ii 73
Focal Facial Dermal Dysplasia Type 2 52
Ffdd Type Ii 73
Ffdd Type 2 52

Characteristics:

Orphanet epidemiological data:

58
focal facial dermal dysplasia type iii
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Antenatal,Neonatal; Age of death: any age;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
heterozygotes may exhibit syndromic manifestations


HPO:

31
focal facial dermal dysplasia 3, setleis type:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare skin diseases
Developmental anomalies during embryogenesis


External Ids:

OMIM 56 227260
OMIM Phenotypic Series 56 PS136500
MeSH 43 D004476
MESH via Orphanet 44 C536385
UMLS via Orphanet 72 C1744559
Orphanet 58 ORPHA1807
MedGen 41 C1744559
UMLS 71 C1744559

Summaries for Focal Facial Dermal Dysplasia 3, Setleis Type

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1807 Definition Focal facial dermal dysplasia type III (FFDD3) is a rare focal facial dermal dysplasia (FFDD; see this term), characterized primarily by congenital bitemporal scar-like depressions and a typical, but variable facial dysmorphism, which may include distichiasis (upper lids) or lacking eyelashes, slanted eyebrows and a flattened and/or bulbous nasal tip and other features such as a low frontal hairline, sparse hair, redundant skin, epicanthal folds, low-set dysplastic ears, blepharitis and conjunctivitis. Epidemiology FFDD3 is reported in over 20 patients from more than 15 families, but only 4 consanguineous families have had TWIST2 mutations . Clinical description FFDD3 is characterized by congenital bitemporal hypoplastic scar-like lesions resembling forceps marks with typical facial dysmorphic features. In addition, they may have periorbital puffiness (leonine facies), sparse lateral and upward lifting eyebrows, distichiasis (upper lashes), a lack of lower lashes and a prominent upper lip (with an inverted ''V'' contour). Nose abnormalities are very frequent and comprise a flattened and/or bulbous nasal tip with septum extended below the alae nasi. Additional frequent features describe a low frontal hairline, sparse hair, epicanthal folds, blepharitis, conjunctivitis, low-set dysplastic ears, and redundant skin. Other eye abnormalities less often reported include short and/or slanting palpebral fissures, as well as impaired vision, nystagmus , exotropia, hypertelorism and absent meibomian glands. Skin dimples lateral to lips, vertical chin clefts, horizontal chin furrows and linear grooves on forehead occur occasionally. Other features such as a pectum deformities and cardiac and genitorurinary abnormalities are rare. Patients generally have normal growth and development. Heterozygous family members may present with minor manifestations, such as partial absence of lower eyelashes and distichiasis of upper lashes. Developmental delay , severe intellectual disability , behavioral problems, and learning difficulties may be observed. Etiology FFDD3 is caused by homozygous mutations in the TWIST2 gene , which encodes a bHLH transcription factor involved in dermal facial development in mammals. To date two nonsense mutations , c.324C>T (p. Q65X) and c.486C>T (p.Q119X), and two small deletions that caused frameshift mutations , c.168delC (p.S57AfsX45) and c.91delC (p.R31GfsX71), have been reported. However, the majority of unrelated FFDD3 patients evaluated have had normal TWIST2 sequences, indicating the molecular genetic heterogeneity of the disorder. Studies are under way to interrogate whole exome or genome sequencing in these patients and their parents to determine the causative defects. Diagnostic methods FFDD3 is diagnosed in patients bearing autosomal recessive bitemporal scar-like lesions and typical FFDD3 facial features, and is confirmed by genetic testing of TWIST2 . However, many patients with typical FFDD3 features have normal TWIST2 sequences (~80%). Thus, diagnosis is clinically based for most patients on the characteristic bitemporal lesions and facial dysmorphism regardless of inheritance. Also, the facial phenotype may be milder in patients without TWIST2 mutations. Differential diagnosis Differential diagnosis includes FFDD1 and FFDD2 (see these terms). Genetic counseling Many cases are sporadic. Inheritance is autosomal recessive for patients with TWIST2 mutations. Heterozygous parents will have a 1 in 4 risk of an affected child with each pregnancy. For other patients, the inheritance is unclear. Management and treatment Pursed lips and eye abnormalities may be surgically corrected, but there is limited experience with plastic surgery. Prognosis In patients with normal intelligence, normal life span is expected. Patients with developmental delay may have other organ system involvement which may affect health and longevity. Visit the Orphanet disease page for more resources.

MalaCards based summary : Focal Facial Dermal Dysplasia 3, Setleis Type, also known as setleis syndrome, is related to ablepharon-macrostomia syndrome and focal facial dermal dysplasia 1, brauer type. An important gene associated with Focal Facial Dermal Dysplasia 3, Setleis Type is TWIST2 (Twist Family BHLH Transcription Factor 2). Affiliated tissues include skin, eye and testes, and related phenotypes are depressed nasal ridge and downturned corners of mouth

OMIM : 56 The focal dermal dysplasias (FFDDs) are a group of related developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. FFFD3 is an autosomal recessive 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 (summary by Slavotinek et al., 2013). FFDD2 (614973) is characterized by the same facial features as FFDD3, but the inheritance is autosomal dominant. For a classification and a discussion of genetic heterogeneity of FFDD, see FFDD1 (136500). (227260)

UniProtKB/Swiss-Prot : 73 Focal facial dermal dysplasia 3, Setleis type: A form of focal facial dermal dysplasia, a group of developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. FFDD3 is characterized by distinctive bitemporal scar-like depressions resembling forceps marks, and additional facial features, including a coarse and leonine appearance, absent eyelashes on both lids or multiple rows on the upper lids, absent Meibomian glands, slanted eyebrows, chin clefting, and hypo- or hyperpigmentation of the skin. Histologically, the bitemporal lesion is an ectodermal dysplasia with near absence of subcutaneous fat, suggesting insufficient migration of neural crest cells into the frontonasal process and the first branchial arch.

Wikipedia : 74 Setleis syndrome is a cutaneous condition characterized double upper and absent lower lashes. Setleis... more...

Related Diseases for Focal Facial Dermal Dysplasia 3, Setleis Type

Diseases related to Focal Facial Dermal Dysplasia 3, Setleis Type via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 20)
# Related Disease Score Top Affiliating Genes
1 ablepharon-macrostomia syndrome 11.3
2 focal facial dermal dysplasia 1, brauer type 11.2
3 focal facial dermal dysplasia 2, brauer-setleis type 11.2
4 focal facial dermal dysplasia 10.5
5 helix syndrome 10.3
6 autosomal recessive disease 10.2
7 distichiasis 10.1
8 dowling-degos disease 1 10.1
9 anus, imperforate 10.1
10 focal facial dermal dysplasia 4 10.1
11 alacrima, achalasia, and mental retardation syndrome 10.1
12 umbilical hernia 10.1
13 epilepsy 10.1
14 ectodermal dysplasia 10.1
15 focal epilepsy 10.1
16 chronic conjunctivitis 10.1
17 conjunctivitis 10.1
18 skin tag 10.1
19 pathologic nystagmus 10.1
20 pectus carinatum 10.1

Graphical network of the top 20 diseases related to Focal Facial Dermal Dysplasia 3, Setleis Type:



Diseases related to Focal Facial Dermal Dysplasia 3, Setleis Type

Symptoms & Phenotypes for Focal Facial Dermal Dysplasia 3, Setleis Type

Human phenotypes related to Focal Facial Dermal Dysplasia 3, Setleis Type:

58 31 (show all 42)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 depressed nasal ridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0000457
2 downturned corners of mouth 58 31 hallmark (90%) Very frequent (99-80%) HP:0002714
3 prematurely aged appearance 58 31 hallmark (90%) Very frequent (99-80%) HP:0007495
4 aplasia/hypoplasia of the skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0008065
5 redundant skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0001582
6 distichiasis 58 31 frequent (33%) Frequent (79-30%) HP:0009743
7 abnormal hair pattern 58 31 hallmark (90%) Very frequent (99-80%) HP:0010720
8 abnormality of the sacroiliac joint 58 31 hallmark (90%) Very frequent (99-80%) HP:0100781
9 low-set ears 31 hallmark (90%) HP:0000369
10 sparse eyebrow 31 hallmark (90%) HP:0045075
11 trichiasis 31 hallmark (90%) HP:0001128
12 curved linear dimple below the lower lip 31 hallmark (90%) HP:0002055
13 bitemporal forceps marks 31 hallmark (90%) HP:0011336
14 dimple chin 31 hallmark (90%) HP:0010751
15 wide nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0000431
16 short philtrum 58 31 frequent (33%) Frequent (79-30%) HP:0000322
17 highly arched eyebrow 58 31 frequent (33%) Frequent (79-30%) HP:0002553
18 epicanthus 58 31 frequent (33%) Frequent (79-30%) HP:0000286
19 abnormality of the upper urinary tract 58 31 frequent (33%) Frequent (79-30%) HP:0010935
20 anal atresia 58 31 frequent (33%) Frequent (79-30%) HP:0002023
21 sparse lateral eyebrow 58 31 frequent (33%) Frequent (79-30%) HP:0005338
22 sparse lower eyelashes 58 31 frequent (33%) Frequent (79-30%) HP:0007776
23 small earlobe 31 frequent (33%) HP:0000385
24 horizontal nystagmus 31 frequent (33%) HP:0000666
25 ectropion of lower eyelids 31 frequent (33%) HP:0007651
26 generalized hypertrichosis 31 frequent (33%) HP:0004554
27 downslanted palpebral fissures 58 31 occasional (7.5%) Occasional (29-5%) HP:0000494
28 strabismus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000486
29 hypopigmented skin patches 58 31 occasional (7.5%) Occasional (29-5%) HP:0001053
30 lacrimation abnormality 58 31 occasional (7.5%) Occasional (29-5%) HP:0000632
31 multiple cafe-au-lait spots 58 31 occasional (7.5%) Occasional (29-5%) HP:0007565
32 absent earlobe 31 occasional (7.5%) HP:0000387
33 lop ear 31 occasional (7.5%) HP:0000394
34 depressed nasal bridge 31 HP:0005280
35 absent eyelashes 31 HP:0000561
36 periorbital fullness 31 HP:0000629
37 chin dimple 58 Very frequent (99-80%)
38 bulbous nose 31 HP:0000414
39 multiple rows of eyelashes 31 HP:0008496
40 sparse hair 58 Very frequent (99-80%)
41 ectodermal dysplasia 31 HP:0000968
42 aged leonine appearance 31 HP:0008509

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
absent eyelashes
multiple rows of eyelashes
puckered skin about the eyes
eyebrows slanted upward
periorbital puffiness

Abdomen Gastrointestinal:
imperforate anus

Skin Nails Hair Skin:
rubbery feel of the nose and chin

Head And Neck Face:
aged leonine appearance
increased mobility of facial skin
redundant facial soft tissue
bilateral temporal marks

Head And Neck Nose:
flat nasal bridge
bulbous nasal tip

Clinical features from OMIM:

227260

Drugs & Therapeutics for Focal Facial Dermal Dysplasia 3, Setleis Type

Search Clinical Trials , NIH Clinical Center for Focal Facial Dermal Dysplasia 3, Setleis Type

Genetic Tests for Focal Facial Dermal Dysplasia 3, Setleis Type

Anatomical Context for Focal Facial Dermal Dysplasia 3, Setleis Type

MalaCards organs/tissues related to Focal Facial Dermal Dysplasia 3, Setleis Type:

40
Skin, Eye, Testes

Publications for Focal Facial Dermal Dysplasia 3, Setleis Type

Articles related to Focal Facial Dermal Dysplasia 3, Setleis Type:

(show all 32)
# Title Authors PMID Year
1
Setleis syndrome in Mexican-Nahua sibs due to a homozygous TWIST2 frameshift mutation and partial expression in heterozygotes: review of the focal facial dermal dysplasias and subtype reclassification. 61 56 6
21931173 2011
2
Homozygous nonsense mutations in TWIST2 cause Setleis syndrome. 61 56 6
20691403 2010
3
Setleis syndrome: autosomal recessive or autosomal dominant inheritance? 61 56 6
8818454 1996
4
CONGENITAL ECTODERMAL DYSPLASIA OF THE FACE. 56 6
14069095 1963
5
Setleis syndrome due to inheritance of the 1p36.22p36.21 duplication: evidence for lack of penetrance. 61 56
26311541 2015
6
Chromosome 1p36.22p36.21 duplications/triplication causes Setleis syndrome (focal facial dermal dysplasia type III). 61 56
25728400 2015
7
Follow-up study in a patient with Setleis syndrome. 61 56
7677148 1995
8
Setleis bitemporal "forceps marks" syndrome and its pathogenesis: a case report. 61 56
1957643 1991
9
Expanded phenotype and ethnicity in Setleis syndrome. 61 56
2596524 1989
10
Autosomal recessive inheritance in the Setleis bitemporal 'forceps marks' syndrome. 61 56
3631024 1987
11
Focal facial dermal dysplasia, type IV, is caused by mutations in CYP26C1. 56
23161670 2013
12
Bitemporal aplasia cutis congenita. Occurrence with other cutaneous abnormalities. 56
4412216 1974
13
Letter: Emendation to "bitemporal aplasia cutis congenita". 56
4414211 1974
14
The TWIST2 mutation causes Setleis syndrome: a rare clinical case report. 61
27750268 2017
15
Barber-Say syndrome and Ablepharon-Macrostomia syndrome: An overview. 61
27196381 2016
16
Setleis syndrome: clinical, molecular and structural studies of the first TWIST2 missense mutation. 61
25410422 2015
17
Biological function and molecular mechanism of Twist2. 61
25608809 2015
18
Setleis syndrome: genetic and clinical findings in a new case with epilepsy. 61
24486222 2014
19
A novel frameshift mutation in TWIST2 gene causing Setleis syndrome. 61
24127007 2014
20
Nonsense mutations of the bHLH transcription factor TWIST2 found in Setleis Syndrome patients cause dysregulation of periostin. 61
21801849 2011
21
Autosomal dominant inheritance in a large family with focal facial dermal dysplasia (Brauer-Setleis syndrome). 61
19291768 2009
22
Ophthalmic findings in Setleis syndrome: two new cases in a mother and son. 61
17508049 2007
23
What syndrome is this? Setleis syndrome. 61
14871335 2004
24
Setleis syndrome: three new cases and a review of the literature. 61
12210295 2002
25
Treatment of Setleis syndrome. Case report. 61
11291343 2001
26
Recurrent digital fibroma, focal dermal hypoplasia, and limb malformations. 61
10982965 2000
27
Absent meibomian glands in Setleis syndrome. 61
9430065 1997
28
Setleis' bitemporal "forceps marks" syndrome in a Japanese family. 61
8651029 1995
29
Autosomal dominant inheritance in Setleis syndrome. 61
7645599 1995
30
Evidence for genetic homogeneity of Setleis' syndrome and focal facial dermal dysplasia. 61
8204474 1994
31
The focal facial dermal dysplasias: report of a kindred and a proposed new classification. 61
1401310 1992
32
Setleis (bitemporal 'forceps marks') syndrome in a German family: evidence for autosomal dominant inheritance. 61
1342863 1992

Variations for Focal Facial Dermal Dysplasia 3, Setleis Type

ClinVar genetic disease variations for Focal Facial Dermal Dysplasia 3, Setleis Type:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TWIST2 NM_001271893.4(TWIST2):c.355C>T (p.Gln119Ter)SNV Pathogenic 30678 rs387906973 2:239757211-239757211 2:238848570-238848570
2 TWIST2 NM_001271893.4(TWIST2):c.193C>T (p.Gln65Ter)SNV Pathogenic 30679 rs387906974 2:239757049-239757049 2:238848408-238848408
3 TWIST2 NM_001271893.4(TWIST2):c.168del (p.Ser57fs)deletion Pathogenic 39840 2:239757021-239757021 2:238848380-238848380

UniProtKB/Swiss-Prot genetic disease variations for Focal Facial Dermal Dysplasia 3, Setleis Type:

73
# Symbol AA change Variation ID SNP ID
1 TWIST2 p.Leu109Pro VAR_072927

Expression for Focal Facial Dermal Dysplasia 3, Setleis Type

Search GEO for disease gene expression data for Focal Facial Dermal Dysplasia 3, Setleis Type.

Pathways for Focal Facial Dermal Dysplasia 3, Setleis Type

GO Terms for Focal Facial Dermal Dysplasia 3, Setleis Type

Sources for Focal Facial Dermal Dysplasia 3, Setleis Type

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