MCID: FCL045
MIFTS: 29

Focal Facial Dermal Dysplasia 3, Setleis Type

Categories: Genetic diseases, Rare diseases, Skin diseases, Fetal 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 57 59 75 13
Setleis Syndrome 57 76 53 59 75
Bitemporal Forceps Marks Syndrome 57 53 75
Facial Ectodermal Dysplasia 57 53 75
Ffdd3 57 59 75
Focal Facial Dermal Dysplasia Type Iii 59 75
Ffdd Type Iii 59 75
Focal Facial Dermal Dysplasia, Type Ii, Formerly 57
Dysplasia, Dermal, Focal Facial, Type 3 40
Congenital Ectodermal Dysplasia of Face 73
Focal Facial Dermal Dysplasia Type Ii 75
Focal Facial Dermal Dysplasia Type 2 53
Ffdd Type Ii 75
Ffdd Type 2 53

Characteristics:

Orphanet epidemiological data:

59
focal facial dermal dysplasia type iii
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Antenatal,Neonatal; Age of death: any age;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
heterozygotes may exhibit syndromic manifestations


HPO:

32
focal facial dermal dysplasia 3, setleis type:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 227260
Orphanet 59 ORPHA1807
MESH via Orphanet 45 C536385
UMLS via Orphanet 74 C1744559
MedGen 42 C1744559
MeSH 44 D004476
UMLS 73 C1744559

Summaries for Focal Facial Dermal Dysplasia 3, Setleis Type

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1807Disease definitionFocal facial dermal dysplasia type III (FFDD3) is a rare focal facial facial 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.EpidemiologyFFDD3 is reported in over 20 patients from more than 15 families, but only 4 consanguineous families have had TWIST2 mutations.Clinical descriptionFFDD3 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.EtiologyFFDD3 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 genomesequencing in these patients and their parents to determine the causative defects.Diagnostic methodsFFDD3 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 diagnosisDifferential diagnosis includes FFDD1 and FFDD2 (see these terms).Genetic counselingMany 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 treatmentPursed lips and eye abnormalities may be surgically corrected, but there is limited experience with plastic surgery.PrognosisIn 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 focal facial dermal dysplasia 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 wide nasal bridge and strabismus

OMIM : 57 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 : 75 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 : 76 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:

# Related Disease Score Top Affiliating Genes
1 focal facial dermal dysplasia 11.2
2 focal facial dermal dysplasia 1, brauer type 10.9
3 focal facial dermal dysplasia 2, brauer-setleis type 10.9

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

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
multiple rows of eyelashes
absent eyelashes
puckered skin about the eyes
eyebrows slanted upward
periorbital puffiness

Head And Neck Nose:
flat nasal bridge
bulbous nasal tip

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

Abdomen Gastrointestinal:
imperforate anus

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


Clinical features from OMIM:

227260

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

59 32 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 wide nasal bridge 59 32 frequent (33%) Frequent (79-30%) HP:0000431
2 strabismus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000486
3 epicanthus 59 32 frequent (33%) Frequent (79-30%) HP:0000286
4 hypopigmented skin patches 59 32 occasional (7.5%) Occasional (29-5%) HP:0001053
5 abnormality of the upper urinary tract 59 32 frequent (33%) Frequent (79-30%) HP:0010935
6 short philtrum 59 32 frequent (33%) Frequent (79-30%) HP:0000322
7 depressed nasal ridge 59 32 hallmark (90%) Very frequent (99-80%) HP:0000457
8 downslanted palpebral fissures 59 32 occasional (7.5%) Occasional (29-5%) HP:0000494
9 prematurely aged appearance 59 32 hallmark (90%) Very frequent (99-80%) HP:0007495
10 multiple cafe-au-lait spots 59 32 occasional (7.5%) Occasional (29-5%) HP:0007565
11 aplasia/hypoplasia of the skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0008065
12 anal atresia 59 32 frequent (33%) Frequent (79-30%) HP:0002023
13 downturned corners of mouth 59 32 hallmark (90%) Very frequent (99-80%) HP:0002714
14 lacrimation abnormality 59 32 occasional (7.5%) Occasional (29-5%) HP:0000632
15 abnormal hair pattern 59 32 hallmark (90%) Very frequent (99-80%) HP:0010720
16 redundant skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0001582
17 highly arched eyebrow 59 32 frequent (33%) Frequent (79-30%) HP:0002553
18 distichiasis 59 32 frequent (33%) Frequent (79-30%) HP:0009743
19 sparse lateral eyebrow 59 32 frequent (33%) Frequent (79-30%) HP:0005338
20 sparse lower eyelashes 59 32 frequent (33%) Frequent (79-30%) HP:0007776
21 abnormality of the sacroiliac joint 59 32 hallmark (90%) Very frequent (99-80%) HP:0100781
22 depressed nasal bridge 32 HP:0005280
23 periorbital fullness 32 HP:0000629
24 bulbous nose 32 HP:0000414
25 multiple rows of eyelashes 32 HP:0008496
26 sparse hair 59 Very frequent (99-80%)
27 absent eyelashes 32 HP:0000561
28 chin dimple 59 Very frequent (99-80%)
29 ectodermal dysplasia 32 HP:0000968
30 aged leonine appearance 32 HP:0008509
31 dimple chin 32 hallmark (90%) HP:0010751

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:

41
Skin, Eye, Testes

Publications for Focal Facial Dermal Dysplasia 3, Setleis Type

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

# Title Authors Year
1
Chromosome 1p36.22p36.21 duplications/triplication causes Setleis syndrome (focal facial dermal dysplasia type III). ( 25728400 )
2015
2
Setleis syndrome: clinical, molecular and structural studies of the first TWIST2 missense mutation. ( 25410422 )
2014
3
Nonsense mutations of the bHLH transcription factor TWIST2 found in Setleis Syndrome patients cause dysregulation of periostin. ( 21801849 )
2011
4
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. ( 21931173 )
2011
5
Homozygous nonsense mutations in TWIST2 cause Setleis syndrome. ( 20691403 )
2010
6
Autosomal dominant inheritance in a large family with focal facial dermal dysplasia (Brauer-Setleis syndrome). ( 19291768 )
2009
7
Setleis syndrome: three new cases and a review of the literature. ( 12210295 )
2002
8
Evidence for genetic homogeneity of Setleis' syndrome and focal facial dermal dysplasia. ( 8204474 )
1994

Variations for Focal Facial Dermal Dysplasia 3, Setleis Type

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

75
# Symbol AA change Variation ID SNP ID
1 TWIST2 p.Leu109Pro VAR_072927

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

6
# Gene Variation Type Significance SNP ID Assembly Location
1 TWIST2 NM_057179.2(TWIST2): c.355C> T (p.Gln119Ter) single nucleotide variant Pathogenic rs387906973 GRCh37 Chromosome 2, 239757211: 239757211
2 TWIST2 NM_057179.2(TWIST2): c.355C> T (p.Gln119Ter) single nucleotide variant Pathogenic rs387906973 GRCh38 Chromosome 2, 238848570: 238848570
3 TWIST2 NM_057179.2(TWIST2): c.193C> T (p.Gln65Ter) single nucleotide variant Pathogenic rs387906974 GRCh37 Chromosome 2, 239757049: 239757049
4 TWIST2 NM_057179.2(TWIST2): c.193C> T (p.Gln65Ter) single nucleotide variant Pathogenic rs387906974 GRCh38 Chromosome 2, 238848408: 238848408
5 TWIST2 TWIST2, 1-BP DEL, 168C deletion Pathogenic

Expression for Focal Facial Dermal Dysplasia 3, Setleis Type

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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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