Details of Disease

General Information of Disease (ID: DISLRS4M)

• Disease Name: Ectodermal dysplasia
• Synonyms: congenital ectodermal defect; ectodermal dysplasia; ectodermal dysplasia (select examples)
• Disease Class: LD27: Skin/mucosal anomaly
• Definition: The term ''ectodermal dysplasia'' defines a heterogeneous group of heritable disorders of the skin and its appendages characterized by the defective development of two or more ectodermal derivatives, including hair, teeth, nails, sweat glands and their modified structures (i.e. ceruminous, mammary and ciliary glands). The spectrum of clinical manifestations is wide and may include additional manifestations from other ectodermal, mesodermal and endodermal structures.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISQNSIX: Hereditary epidermal appendage anomaly
  DISSCALK: Hereditary skin disorder
  DISLRS4M: Ectodermal dysplasia
• ICD Code:
  ICD-11: ICD-11: LD27.0
  ICD-10: ICD-10: Q77.6, Q82.8
  Expand ICD-11: 'LD27.0
  Expand ICD-10: 'Q77.6; 'Q82.8
• Disease Identifiers:
  MONDO ID: MONDO_0019287
  MESH ID: D004476
  UMLS CUI: C0013575
  MedGen ID: 8544
  HPO ID: HP:0000968
  Orphanet ID: 79373
  SNOMED CT ID: 254154003

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
EDI1200	DMTY1G8	Phase 2	NA	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 13 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
NFKBIA	TTSHAEB	Limited	Genetic Variation	[2]
RPE65	TTBOH16	Limited	Genetic Variation	[3]
CHUK	TT1F8OQ	Strong	Biomarker	[4]
CTSC	TTQ9J6R	Strong	Autosomal recessive	[5]
GJB6	TTAU8SJ	Strong	Genetic Variation	[6]
ITCH	TT5SEWD	Strong	Biomarker	[7]
NECTIN4	TTPO9EG	Strong	Genetic Variation	[8]
NFKB2	TTKLNRV	Strong	Biomarker	[9]
ODC1	TTUMGNO	Strong	Biomarker	[10]
RHOA	TTP2U16	Strong	Biomarker	[11]
TRAF6	TTCDR6M	Strong	Biomarker	[12]
MAP3K7	TTJQT60	Definitive	Biomarker	[12]
ORAI1	TTE76YK	Definitive	Genetic Variation	[13]

This Disease Is Related to 23 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CKAP4	OTDUC9ME	Limited	Genetic Variation	[3]
DLX3	OTARP5SQ	Limited	Genetic Variation	[14]
EDARADD	OT0G52MC	Limited	Genetic Variation	[15]
FNDC3A	OTUX3S2I	Disputed	Biomarker	[16]
EDAR	OT3W2UQS	moderate	Genetic Variation	[17]
HOXC13	OT52AVNA	moderate	Genetic Variation	[18]
ITGB4	OT28UK84	moderate	Biomarker	[19]
AXIN2	OTRMGQNU	Strong	Genetic Variation	[20]
CTSC	OT79WJZZ	Strong	Autosomal recessive	[5]
EDA2R	OTJLAIIH	Strong	Biomarker	[21]
IKBKG	OTNWJWSD	Strong	Genetic Variation	[22]
KDF1	OTNMH6OS	Strong	Biomarker	[23]
KREMEN1	OTGJFSAC	Strong	Genetic Variation	[24]
KRT74	OT9MEIJ1	Strong	Genetic Variation	[25]
NECTIN1	OTTE5ZR6	Strong	Genetic Variation	[26]
PAX9	OT25J0F7	Strong	Biomarker	[27]
PERP	OTP0YL53	Strong	Biomarker	[28]
PKP1	OT9HSQ8F	Strong	Genetic Variation	[29]
KRT14	OTUVZ1DW	Definitive	Biomarker	[30]
KRT85	OT67IP7F	Definitive	Genetic Variation	[31]
SMARCAD1	OT90AZTX	Definitive	Autosomal dominant	[32]
STIM1	OT8CLQ1W	Definitive	Biomarker	[13]
TAB2	OTPZK76F	Definitive	Biomarker	[12]

References

• [1] Clinical pipeline report, company report or official report of Edimer pharmaceuticals.
• [2] A novel NFKBIA variant substituting serine 36 of IB causes immunodeficiency with warts, bronchiectasis and juvenile rheumatoid arthritis in the absence of ectodermal dysplasia.Clin Immunol. 2020 Jan;210:108269. doi: 10.1016/j.clim.2019.108269. Epub 2019 Nov 1.
• [3] DLX5, FGF8 and the Pin1 isomerase control Np63 protein stability during limb development: a regulatory loop at the basis of the SHFM and EEC congenital malformations.Hum Mol Genet. 2014 Jul 15;23(14):3830-42. doi: 10.1093/hmg/ddu096. Epub 2014 Feb 25.
• [4] Defective nuclear IKK function in patients with ectodermal dysplasia with immune deficiency.J Clin Invest. 2012 Jan;122(1):315-26. doi: 10.1172/JCI42534. Epub 2011 Dec 12.
• [5] Novel point mutations, deletions, and polymorphisms in the cathepsin C gene in nine families from Europe and North Africa with Papillon-Lefvre syndrome. J Invest Dermatol. 2001 Dec;117(6):1657-61. doi: 10.1046/j.0022-202x.2001.01595.x.
• [6] A novel connexin 30 mutation in Clouston syndrome.J Invest Dermatol. 2002 Mar;118(3):530-2. doi: 10.1046/j.0022-202x.2001.01689.x.
• [7] Recognition of p63 by the E3 ligase ITCH: Effect of an ectodermal dysplasia mutant.Cell Cycle. 2010 Sep 15;9(18):3730-9. Epub 2010 Sep 8.
• [8] A novel homozygous missense variant in NECTIN4 (PVRL4) causing ectodermal dysplasia cutaneous syndactyly syndrome.Ann Hum Genet. 2018 Jul;82(4):232-238. doi: 10.1111/ahg.12244. Epub 2018 Feb 12.
• [9] Pathogenic NFKB2 variant in the ankyrin repeat domain (R635X) causes a variable antibody deficiency.Clin Immunol. 2019 Jun;203:23-27. doi: 10.1016/j.clim.2019.03.010. Epub 2019 Apr 3.
• [10] Gain-of-function variants in the ODC1 gene cause a syndromic neurodevelopmental disorder associated with macrocephaly, alopecia, dysmorphic features, and neuroimaging abnormalities.Am J Med Genet A. 2018 Dec;176(12):2554-2560. doi: 10.1002/ajmg.a.60677. Epub 2018 Nov 26.
• [11] Postzygotic inactivating mutations of RHOA cause a mosaic neuroectodermal syndrome.Nat Genet. 2019 Oct;51(10):1438-1441. doi: 10.1038/s41588-019-0498-4. Epub 2019 Sep 30.
• [12] [New genes candidates for ectodermal dysplasia: TAB2, TRAF6 and TAK1].Med Sci (Paris). 2006 Mar;22(3):229-30. doi: 10.1051/medsci/2006223229.
• [13] Stim1 Regulates Enamel Mineralization and Ameloblast Modulation.J Dent Res. 2017 Nov;96(12):1422-1429. doi: 10.1177/0022034517719872. Epub 2017 Jul 21.
• [14] A dominant mutation etiologic for human tricho-dento-osseous syndrome impairs the ability of DLX3 to downregulate Np63.J Cell Physiol. 2011 Aug;226(8):2189-97. doi: 10.1002/jcp.22553.
• [15] From ectodermal dysplasia to selective tooth agenesis.Am J Med Genet A. 2009 Sep;149A(9):2037-41. doi: 10.1002/ajmg.a.32801.
• [16] A novel mutation in NFKBIA/IKBA results in a degradation-resistant N-truncated protein and is associated with ectodermal dysplasia with immunodeficiency. Hum Mutat. 2008 Jun;29(6):861-8. doi: 10.1002/humu.20740.
• [17] The transcription factor NKX2-3 mediates p21 expression and ectodysplasin-A signaling in the enamel knot for cusp formation in tooth development.J Biol Chem. 2018 Sep 21;293(38):14572-14584. doi: 10.1074/jbc.RA118.003373. Epub 2018 Aug 8.
• [18] The disrupted balance between hair follicles and sebaceous glands in Hoxc13-ablated rabbits.FASEB J. 2019 Jan;33(1):1226-1234. doi: 10.1096/fj.201800928RR. Epub 2018 Aug 20.
• [19] Deletion of the first pair of fibronectin type III repeats of the integrin beta-4 gene is associated with epidermolysis bullosa, pyloric atresia and aplasia cutis congenita in the original Carmi syndrome patients.Am J Med Genet A. 2008 Apr 15;146A(8):1063-6. doi: 10.1002/ajmg.a.31903.
• [20] Phenotypic confirmation of oligodontia, colorectal polyposis and cancer in a family carrying an exon 7 nonsense variant in the AXIN2 gene.Fam Cancer. 2019 Jul;18(3):311-315. doi: 10.1007/s10689-019-00120-0.
• [21] Role of TRAF3 and -6 in the activation of the NF-kappa B and JNK pathways by X-linked ectodermal dysplasia receptor.J Biol Chem. 2002 Nov 22;277(47):44953-61. doi: 10.1074/jbc.M207923200. Epub 2002 Sep 20.
• [22] Functional Evaluation of an IKBKG Variant Suspected to Cause Immunodeficiency Without Ectodermal Dysplasia.J Clin Immunol. 2017 Nov;37(8):801-810. doi: 10.1007/s10875-017-0448-9. Epub 2017 Oct 10.
• [23] KDF1, encoding keratinocyte differentiation factor 1, is mutated in a multigenerational family with ectodermal dysplasia. Hum Genet. 2017 Jan;136(1):99-105. doi: 10.1007/s00439-016-1741-z. Epub 2016 Nov 12.
• [24] Mutation of KREMEN1, a modulator of Wnt signaling, is responsible for ectodermal dysplasia including oligodontia in Palestinian families.Eur J Hum Genet. 2016 Oct;24(10):1430-5. doi: 10.1038/ejhg.2016.29. Epub 2016 Apr 6.
• [25] Autosomal recessive transmission of a rare KRT74 variant causes hair and nail ectodermal dysplasia: allelism with dominant woolly hair/hypotrichosis. PLoS One. 2014 Apr 8;9(4):e93607. doi: 10.1371/journal.pone.0093607. eCollection 2014.
• [26] Nectin-4 mutations causing ectodermal dysplasia with syndactyly perturb the rac1 pathway and the kinetics of adherens junction formation.J Invest Dermatol. 2014 Aug;134(8):2146-2153. doi: 10.1038/jid.2014.119. Epub 2014 Feb 27.
• [27] GREMLIN 2 Mutations and Dental Anomalies.J Dent Res. 2015 Dec;94(12):1646-52. doi: 10.1177/0022034515608168. Epub 2015 Sep 28.
• [28] Differential PERP regulation by TP63 mutants provides insight into AEC pathogenesis.Am J Med Genet A. 2009 Sep;149A(9):1952-7. doi: 10.1002/ajmg.a.32760.
• [29] Ectodermal dysplasia-skin fragility syndrome. Dermatol Clin. 2010 Jan;28(1):125-9. doi: 10.1016/j.det.2009.10.014.
• [30] KRT14 haploinsufficiency results in increased susceptibility of keratinocytes to TNF-alpha-induced apoptosis and causes Naegeli-Franceschetti-Jadassohn syndrome.J Invest Dermatol. 2008 Jun;128(6):1517-24. doi: 10.1038/sj.jid.5701187. Epub 2007 Nov 29.
• [31] Autosomal recessive pure hair and nail ectodermal dysplasia linked to chromosome 12p11.1-q14.3 without KRTHB5 gene mutation.Eur J Dermatol. 2010 Jul-Aug;20(4):443-6. doi: 10.1684/ejd.2010.0962. Epub 2010 Apr 21.
• [32] SMARCAD1 Haploinsufficiency Underlies Huriez Syndrome and Associated Skin Cancer?Susceptibility. J Invest Dermatol. 2018 Jun;138(6):1428-1431. doi: 10.1016/j.jid.2018.01.015. Epub 2018 Feb 1.