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Cited by 181dental development and anomaliesGenetic and rare skin diseases.Hair Growth and Disorders

Ectodermal dysplasias: Clinical and molecular review

Open access
Visinoni, Átila F., Lisboa‐Costa, Toni, Pagnan, Nina A.B., Chautard‐Freire‐Maia, Eleidi A.·2009·American Journal of Medical Genetics Part A
DOI 10.1002/ajmg.a.32864
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Abstract

Ectodermal dysplasias (EDs) are congenital disorders characterized by alterations in two or more ectodermal structures.

Integrity signals

Registry

Crossref · 10.1002/ajmg.a.32864

Cites

88 of 88 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

4 of 39 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    The four genes causing cardiofaciocutaneous syndrome (BRAF, KRAS2, MEK1, MEK2) all belong to the same RAS-extracellular signal-regulated kinase (ERK) pathway.

    “The cardiofaciocutaneous syndrome (CFC, OMIM 115150) is caused by gain-of function mutations in 4 different genes BRAF (7q34), KRAS2 (12p12.1),MEK1 (15q21), and MEK2 (7q32), all belonging to the same RAS-extracellular signal-regulated kinase (ERK) pathway that regulates cell differentiation, proliferation, and apoptosis [Roberts et al., 2006].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Roberts et al., 2006 source
  • Premisecitation

    The other classifications being proposed use molecular knowledge as the starting point.

    “The other classifications which are being proposed [Priolo et al., 2000;Priolo and Lagan a, 2001;Lamartine, 2003;Itin and Fistarol, 2004] use molecular knowledge as the starting point.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Priolo et al., 2000 source
    • cites Priolo and Lagan a, 2001 source
    • cites Lamartine, 2003 source
  • Premisecitation

    The RAS-extracellular signal-regulated kinase (ERK) pathway regulates cell differentiation, proliferation, and apoptosis.

    “The cardiofaciocutaneous syndrome (CFC, OMIM 115150) is caused by gain-of function mutations in 4 different genes BRAF (7q34), KRAS2 (12p12.1),MEK1 (15q21), and MEK2 (7q32), all belonging to the same RAS-extracellular signal-regulated kinase (ERK) pathway that regulates cell differentiation, proliferation, and apoptosis [Roberts et al., 2006].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Roberts et al., 2006 source
  • Findingcitation

    The cardiofaciocutaneous syndrome (CFC, OMIM 115150) is caused by gain-of-function mutations in four different genes: BRAF (7q34), KRAS2 (12p12.1), MEK1 (15q21), and MEK2 (7q32).

    “The cardiofaciocutaneous syndrome (CFC, OMIM 115150) is caused by gain-of function mutations in 4 different genes BRAF (7q34), KRAS2 (12p12.1),MEK1 (15q21), and MEK2 (7q32), all belonging to the same RAS-extracellular signal-regulated kinase (ERK) pathway that regulates cell differentiation, proliferation, and apoptosis [Roberts et al., 2006].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Roberts et al., 2006 source

      The Abstract (page unavailable) states that CFC is caused by gain-of-function mutations in BRAF, KRAS, MEK1 and MEK2, and places them in the RAS–ERK pathway. The cited copy does not provide the chromosome-band locations in the claim or use the name KRAS2, so those details are not verified by this source. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Findingnone given

    Nonphotosensitive trichothiodystrophy (TTD, OMIM 234050) includes Sabinas brittle hair syndrome and trichorrhexis nodosa syndrome (Pollitt syndrome).

    “Nonphotosensitive trichothiodystrophy (TTD, OMIM 234050) includes two other EDs: Sabinas brittle hair syndrome (OMIM 211390) and trichorrhexis nodosa syndrome (Pollitt syndrome, OMIM 275550).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 18
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 15

  • May combine two claims.

    Findingcitation

    Zanier-Roubicek syndrome is the autosomal dominant form of hypohidrotic ectodermal dysplasia (ADHED, OMIM 129490), caused by mutations in the EDAR or EDARADD genes.

    “The Zanier-Roubicek syndrome [Zanier and Roubicek, 1976] is the AD form of hypohidrotic ectodermal dysplasia (ADHED, OMIM 129490), caused by mutations in the EDAR or EDARADD genes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zanier and Roubicek, 1976

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingcitation

    Irvine (2005) reviewed 141 ectodermal dysplasias, 6 belonging to the B group.

    “On the other hand, Irvine [2005] reviewed 141 EDs, 6 belonging to the B group.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Irvine, 2005

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • The quote only partly states this claim.

    Findingreasoning

    Dyskeratosis congenita presents three inheritance patterns: X-linked, autosomal recessive, and autosomal dominant.

    “Dyskeratosis congenita presents three inheritance patterns.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Table III updates previous reviews, adding almost 50 genes to those reported by Lamartine (2003).

    “Table III updates previous reviews [Priolo et al., 2000;Priolo and Lagan a, 2001;Lamartine, 2003;Itin and Fistarol, 2004], adding almost 50 genes in those reported by Lamartine [2003], whose functional classification was followed.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Priolo et al., 2000 source
    • cites Lamartine, 2003 source
    • cites Itin and Fistarol, 2004 source

  • May combine two claims.

    Findingcitation

    Tricho-dermodysplasia-dental defects, tricho-odonto-onycho-dermal syndrome, and trichoodontoonychial dysplasia present similar signs and were each observed in only one family.

    “The following EDs present similar signs: tricho-dermodysplasiadental defects [Pinheiro et al., 1986], tricho-odonto-onycho-dermal syndrome [Pinheiro et al., 1981] and trichoodontoonychial dysplasia (OMIM 275450) all of them observed in only one family.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Pinheiro et al., 1986 source
    • cites Pinheiro et al., 1981 source

  • May combine two claims.

    Findingnone given

    Patients with Lelis syndrome present hypohidrosis and hyperkeratosis palmoplantaris, whereas ED with natal teeth Turnpenny type does not manifest these signs.

    “Patients with Lelis syndrome present hypohidrosis and hyperkeratosis palmoplantaris whereas the Turnpenny type does not manifest these signs.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    The last revision by Pinheiro and Freire-Maia (1994) listed 154 entities of the A group.

    “The last revision by Pinheiro and Freire-Maia [1994] listed 154 entities of the A group.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Pinheiro and Freire-Maia, 1994 source

  • May combine two claims.

    Findingreasoning

    Clouston syndrome shows hyperkeratosis as in Lelis syndrome and resembles Turnpenny type in normal hidrosis.

    “Clouston syndrome shows hyperkeratosis as in Lelis syndrome and resembles Turnpenny type in normal hidrosis what stresses the similarities among these three syndromes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    Mutations in the NEMO gene cause hypohidrotic ED with immune deficiency, incontinentia pigmenti 2, and OLEDAID syndrome.

    “Mutations in the NEMO gene cause hypohidrotic ED with immune deficiency (OMIM 300291), incontinentia pigmenti 2 (OMIM 308300) and hypohidrotic ED with immunodeficiency, osteopetrosis and lymphedema (OLEDAID syndrome, OMIM 300301).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: IKK-g, encoded by the NEMO gene, is an important regulator of the NF-kB pathway.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    Monilethrix (OMIM 158000) is caused by mutations in genes responsible for hair keratin: KRTHB1, KRTHB3, and KRTHB6 (all in 12q13).

    “Monilethrix (OMIM 158000) is caused by mutations in genes responsible for hair keratin: KRTHB1, KRTHB3, and KRTHB6 (all in 12q13).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Three hypohidrotic ectodermal dysplasias (X-linked HED, autosomal dominant HED, and autosomal recessive HED) show identical clinical manifestation but different inheritance patterns.

    “There is an unusual situation in which three hypohidrotic EDs (HED) show identical clinical manifestation but different inheritance patterns, being classified as separate entities: X-linked HED (OMIM 305100), autosomal dominant (ADHED, OMIM 129490) and autosomal recessive (ARHED, OMIM 224900).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    Two conditions for which only clinical subgroups and chromosomal regions were assigned were not included in Table I, as they may represent previously described EDs.

    “Two conditions (Table III) for which only the clinical subgroups and chromosomal regions were assigned [Rafiq et al., 2005;Tariq et al., 2008] were not included in Table I, as they may represent previously described EDs.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Rafiq et al., 2005 source
    • cites Tariq et al., 2008 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The autosomal dominant form of dyskeratosis congenita (OMIM 127550) may be caused by mutations in TERC (3q21-q28), TERT (5p15.33), or TINF (14q12).

    “On the other hand, the AD form (OMIM 127550) may be caused by mutations in the three following genes: TERC (3q21-q28) that codes for a telomerase RNA component; TERT (5p15.33)that determines a telomerase reverse transcriptase; and TINF (14q12) that codes for an interacting nuclear factor.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Fried tooth and nail syndrome is a hidrotic ectodermal dysplasia that seems to overlap with Witkop syndrome, which has an autosomal dominant inheritance pattern.

    “Fried tooth and nail syndrome [Fried, 1977] is a hidrotic ED that seems to overlap with Witkop syndrome (OMIM 189500) which presents an AD inheritance pattern.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Fried, 1977 source

  • May combine two claims.

    Interpretationreasoning

    Fried syndrome may be the same entity as hidrotic ectodermal dysplasia, whereas Witkop syndrome represents another entity.

    “Considering the AR inheritance pattern, we suggest that Fried syndrome may be the same entity as hidrotic ED whereas Witkop syndrome represents another entity.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    The clinical classification will clearly delineate the condition and allow a rapid diagnosis.

    “The clinical classification will clearly delineate the condition and allow a rapid diagnosis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    The X-linked form of hypomelanosis of Ito is incontinentia pigmenti 1 (IP1), but the autosomal dominant hypomelanosis of Ito is Naegeli-Franceschetti-Jadassohn syndrome.

    “In our opinion, The X-linked form is actually IP1, but the AD hypomelanosis of Ito is the Naegeli-Franceschetti-Jadassohn syndrome (OMIM 161000).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    Mutations in one gene cause clinically different ectodermal dysplasias, and mutations in different genes can determine the same ED entity.

    “However, mutations in one gene cause clinically different EDs and mutations in different genes can determine the same ED entity, as will be discussed.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Pachyonychia congenita, incontinentia pigmenti, and dyskeratosis congenita are EDs by definition, but common practice has considered them separate entities.

    “These entities are EDs by definition, but common practice has considered them separate entities [Irvine, 2005].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Irvine, 2005

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    Comprehension of the biological mechanisms that cause ectodermal dysplasias is needed for the design of efficient prevention and treatment approaches.

    “Secondly, the comprehension of the biological mechanisms that cause EDs is needed for the design of efficient prevention and treatment approaches.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Head-to-head configurations such as that of EVC and EVC2 may be common in the human genome.

    “Adachi and Lieber [2002] concluded that such head-to-head configurations may be common in the human genome.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Adachi and Lieber, 2002 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    TERT determines a telomerase reverse transcriptase.

    “On the other hand, the AD form (OMIM 127550) may be caused by mutations in the three following genes: TERC (3q21-q28) that codes for a telomerase RNA component; TERT (5p15.33)that determines a telomerase reverse transcriptase; and TINF (14q12) that codes for an interacting nuclear factor.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    The classification based on molecular aspects is prone to continued additions and modifications due to new discoveries and will provide organized information for new research.

    “The classification based on molecular aspects is prone to continued additions and modifications due to new discoveries and will provide organized information to be used in new researches, such as those on metabolic pathways and embryonic signaling.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    TINF codes for an interacting nuclear factor.

    “On the other hand, the AD form (OMIM 127550) may be caused by mutations in the three following genes: TERC (3q21-q28) that codes for a telomerase RNA component; TERT (5p15.33)that determines a telomerase reverse transcriptase; and TINF (14q12) that codes for an interacting nuclear factor.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Ectodysplasin binds to its receptor EDAR, which recruits the adapter protein EDARADD to transduce a signal and activate NF-kB via the IKK complex.

    “Ectodysplasin binds to its receptor EDAR which recruits the adapter protein EDARADD to transduce a signal and activate NF-kB via the IKK complex [Headon et al., 2001].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Headon et al., 2001 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    TERC codes for a telomerase RNA component.

    “On the other hand, the AD form (OMIM 127550) may be caused by mutations in the three following genes: TERC (3q21-q28) that codes for a telomerase RNA component; TERT (5p15.33)that determines a telomerase reverse transcriptase; and TINF (14q12) that codes for an interacting nuclear factor.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Combining clinical and molecular procedures allows a rapid diagnosis that may become more precise whenever DNA exams are available.

    “First, it allows a rapid diagnosis that may become even more precise whenever DNA exams are available.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    Both definition and classification of ectodermal dysplasias are dynamic and require re-evaluation from time to time.

    “Adding the fact that new discoveries are constantly made, it is evident that both definition and classification of EDs are dynamic and their re-evaluation is required from time to time.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    Molecular research leads to the discovery of gene defects responsible for ectodermal dysplasias and provides causal diagnosis that may reduce the number of classified entities when EDs described as different clinical disturbances are shown to represent variable expressivity of the same ED.

    “Researches at the molecular level lead to the discovery of gene defects responsible for EDs and provide the causal diagnosis that may reduce the number of classified entities whenever EDs described as different clinical disturbances are shown to represent variable expressivity of the same ED.”
    Quote in the paperSubstantial claim
29 of 29

  • The paper relies on this without support.

    IKK-g, encoded by the NEMO gene, is an important regulator of the NF-kB pathway.

    “IKK-g, encoded by the NEMO gene (Xq28), is an important regulator of the NF-kB pathway.”

  • The paper relies on this without support.

    The TP63 gene encodes several isoforms with divergent abilities to transactivate P53 reporter genes and induce apoptosis.

    “The TP63 gene, also known as TP73L (3q27) encodes several isoforms with divergent abilities to transactivate P53 reporter genes and induce apoptosis.”

  • The paper relies on this without support.

    Ectodermal dysplasias show variable expression.

    “Considering that EDs show variable expression, it is possible that some of them belong to EDs already established.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A shift has occurred to classifying ectodermal dysplasias based on the genetic defect or developmental pathway involved, which helps in offering a better understanding of these disorders.

    “Continuous revision of the classification systems has been attempted, and a shift has occurred to classifying these disorders based on the genetic defect or the developmental pathway involved which helps in offering a better understanding of these disorders.[4]”

    From Ectodermal Dysplasia – An Overview and Update (2024) · cites this paper as [4]

Cites

Flagged first, then by citations

Research works printed but not linked: 14

  1. Antley RM, 1976, Hypohidrosis with sparse hair, short stature and normal teeth and nails, Birth Defects Orig Artic Ser, 12, 136
  2. Beemer FA, 1987, Two cases of hypotrichosis with pili bifurcati, Am J Med Genet, 4, 187
  3. Beyer P, 1979, Forme inhabituelle de dysplasie ectodermique hypohidrotique avec des glandes sudoripares en nombre apparemment normal, mais dysplasiques et des anomalies morphologiques de la peau, Pédiatrie, 34, 341
  4. Gorlin RJ, 1988, Recent advances in ectodermal dysplasias, 123
  5. Greenstein MA, 1985, Ectodermal dysplasia: A new form and consideration of possible associations, Am J Hum Genet, 37, 56
  6. Irvine AD, 2005, Pediatric dermatology, 1412
  7. Kaplan P, 1995, Evidence that the Setleis and Brauer syndromes of focal dermal hypoplasia are the same entity, Am J Hum Genet, 57, A93
  8. Lenz W, 1963, Medical genetics, 214
  9. Lipson M, 1988, A new type of ectodermal dysplasia associated with skeletal and cardiac abnormalities, Am J Med Genet, 31, 2
  10. Montebelo AF, 1996, Displasia ectodérmica tipo Caratinga, Braz J Genet, 19, 162
  11. Moynahan EJ, 1970, XTE syndrome (xeroderma, talipes and enamel defect): A new heredo‐familial syndrome, Proc R Soc Med, 63, 1
  12. Pinheiro M, 1981, Odonto‐onicodisplasia com alopecia: Dois casos em uma irmandade, Ciênc Cult, 33, 696
  13. Walbaum R, 1971, Dysplasie ectodermique: Une forme autosomique récessive?, Arch Fr Pédiatr, 28, 435
  14. Wiedemann HR, 1980, Características das síndromes em pediatria. Atlas de diagnóstico diferencial”. Transl. Dr. Horst Fürstenau, 195

Cited by

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Related

Authors
Visinoni, Á. F., Lisboa‐Costa, T., Pagnan, N. A. B., & Chautard‐Freire‐Maia, E. A.
Affiliations
Universidade Federal do Paraná (BR)
Corresponding author
Chautard‐Freire‐Maia, Eleidi A.
Venue
American Journal of Medical Genetics Part A
Publisher
Wiley
Published
2009-08-13
Volume
149A
Issue
9
Pages
1980-2002
ISSN
  • 1552-4825 (ISSN-L)
  • 1552-4833
DOI
10.1002/ajmg.a.32864
OpenAlex
W2085811596
Cited by
181
References
87
Citations by year
2026: 7 · 2025: 4 · 2024: 19 · 2023: 6 · 2022: 12 · 2021: 9 · 2020: 9 · 2019: 14 · 2018: 16 · 2017: 10 · 2016: 10 · 2015: 12 · 2014: 15 · 2013: 13 · 2012: 16
FWCI
0.61
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • American Journal of Medical Genetics Part A (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
Keywords
ectodermal dysplasia, clinical classification, molecular genetics, genetic mutations, hair disorders, dental anomalies, nail disorders, sweat gland disorders, genetic diagnosis, congenital disorders
MeSH terms
Child, Preschool, Ectodermal Dysplasia, Genotype, Hair, Humans, Male, Molecular Biology, Phenotype, Skin

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Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

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