Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review

TP63-Related Disorders

V Reid Sutton  1 , Hans van Bokhoven  2
Margaret P Adam, Jerry Feldman, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Anne Amemiya
, editors.
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].
Affiliations
Free Books & Documents
Review

TP63-Related Disorders

V Reid Sutton et al.
Free Books & Documents

Excerpt

Clinical characteristics: The TP63-related disorders comprise six overlapping phenotypes:

  1. Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome (which includes Rapp-Hodgkin syndrome)

  2. Acro-dermo-ungual-lacrimal-tooth (ADULT) syndrome

  3. Ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome 3 (EEC3)

  4. Limb-mammary syndrome

  5. Split-hand/foot malformation type 4 (SHFM4)

  6. Isolated cleft lip/cleft palate (orofacial cleft 8)

Individuals typically have varying combinations of ectodermal dysplasia (hypohidrosis, nail dysplasia, sparse hair, tooth abnormalities), cleft lip/palate, split-hand/foot malformation/syndactyly, lacrimal duct obstruction, hypopigmentation, hypoplastic breasts and/or nipples, and hypospadias. Findings associated with a single phenotype include ankyloblepharon filiforme adnatum (tissue strands that completely or partially fuse the upper and lower eyelids), skin erosions especially on the scalp associated with areas of scarring, and alopecia, trismus, and excessive freckling.

Diagnosis/testing: The diagnosis of a TP63-related disorder is established in a proband with suggestive findings and a heterozygous pathogenic variant in TP63 identified by molecular genetic testing.

Management: Treatment of manifestations: A multidisciplinary team of specialists in clinical genetics, dermatology, ophthalmology, otolaryngology, audiology, dentistry and prosthodontics, plastic surgery, nutrition/gastroenterology, and psychology is recommended. Skin erosions are treated with gentle wound care and periodic, dilute bleach soaks to prevent secondary infection, and infants with severe skin erosions are monitored and treated aggressively for dehydration, electrolyte imbalances, malnutrition, and infection. Wigs can be used for sparse hair and alopecia; dentures may be considered in early childhood and dental implants in the teens or early adulthood. Cleft lip/palate is managed per routine protocols; limb malformations are treated with occupational therapy and surgery as needed to optimize function.

Surveillance: Regular attention to dental needs and possible hearing loss.

Genetic counseling: The TP63-related disorders are inherited in an autosomal dominant manner. Approximately 30% of individuals diagnosed with a TP63-related disorder have an affected parent. The proportion of individuals with a TP63-related disorder caused by a de novo TP63 pathogenic variant is approximately 70%. If a parent of the proband is affected and/or is known to have the pathogenic variant identified in the proband, the risk to the sibs is 50%. Once the TP63 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

PubMed Disclaimer

Similar articles

  • IRF6-Related Disorders.
    Schutte BC, Saal HM, Goudy S, Leslie EJ. Schutte BC, et al. 2003 Oct 30 [updated 2021 Mar 4]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2003 Oct 30 [updated 2021 Mar 4]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301581 Free Books & Documents. Review.
  • PORCN-Related Developmental Disorders.
    Sutton VR. Sutton VR. 2008 May 15 [updated 2023 Jun 15]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2008 May 15 [updated 2023 Jun 15]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301712 Free Books & Documents. Review.
  • Phelan-McDermid Syndrome-SHANK3 Related.
    Phelan K, Rogers RC, Boccuto L. Phelan K, et al. 2005 May 11 [updated 2024 Jun 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2005 May 11 [updated 2024 Jun 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301377 Free Books & Documents. Review.
  • FLNB Disorders.
    Robertson S. Robertson S. 2008 Oct 9 [updated 2020 Feb 13]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2008 Oct 9 [updated 2020 Feb 13]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301736 Free Books & Documents. Review.
  • Apert Syndrome.
    Wenger TL, Hing AV, Evans KN. Wenger TL, et al. 2019 May 30. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2019 May 30. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 31145570 Free Books & Documents. Review.
See all similar articles

References

    1. Amiel J, Bougeard G, Francannet C, Raclin V, Munnich A, Lyonnet S, Frebourg T. TP63 gene mutation in ADULT syndrome. Eur J Hum Genet. 2001;9:642–5. - PubMed
    1. Aradhya S, Lewis R, Bonaga T, Nwokekeh N, Stafford A, Boggs B, Hruska K, Smaoul N, Compton JG, Richard G, Suchy S. Exon-level array CGH in a large clinical cohort demonstrates increased sensitivity of diagnostic testing for Mendelian disorders. Genet Med. 2012;14:594–603. - PubMed
    1. Barrow LL, van Bokhoven H, Daack-Hirsch S, Andersen T, van Beersum SE, Gorlin R, Murray JC. Analysis of the p63 gene in classical EEC syndrome, related syndromes, and non-syndromic orofacial clefts. J Med Genet. 2002;39:559–66. - PMC - PubMed
    1. Basha M, Demeer B, Revencu N, Helaers R, Theys S, Bou Saba S, Boute O, Devauchelle B, Francois G, Bayet B, Vikkula M. Whole exome sequencing identifies mutations in 10% of patients with familial non-syndromic cleft lip and/or palate in genes mutated in well-known syndromes. J Med Genet. 2018;55:449–58. - PubMed
    1. Buss PW, Hughes HE, Clarke A. Twenty-four cases of the EEC syndrome: clinical presentation and management. J Med Genet. 1995;32:716–23. - PMC - PubMed

LinkOut - more resources