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Ectrodactyly-ectodermal dysplasia-clefting syndrome
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Ectrodactyly-ectodermal dysplasia-clefting syndrome

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Contributors: Tyler Werbel, Susan Burgin MD
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Synopsis

There are 6 autosomal dominant p63-associated ectodermal dysplasia syndromes: 
  • Ankyloblepharon-ectodermal dysplasia-cleft lip / palate (AEC)
  • Ectrodactyly-ectodermal-dysplasia-cleft lip / palate (EEC)
  • Acro-dermo-ungual-lacrimal-tooth (ADULT)
  • Limb-mammary
  • Split-hand / foot malformation type 4 (SHFM4)
  • Isolated cleft lip / cleft palate (orofacial cleft 8)
This summary focuses on EEC.

All ectodermal dysplasias result from the abnormal development of structures derived from the outer embryonal layer such as the skin, hair, teeth, nails, and eccrine and sebaceous glands. While these 6 syndromes are classified as distinct entities, their overlapping phenotypes suggest that they may be part of a spectrum of related syndromes.

p63 is a transcription factor with homology to the tumor suppressor p53. Studies in mice have demonstrated that unlike p53, p63 expression is localized to whiskers, oral mucosa, and distal limbs. Furthermore, mice lacking p63 are born with translucent skin and without appendages (whisker pads, teeth). It has been postulated that p63 plays an important role in epidermal stratification and the maintenance of epidermal stem cells.

While all 6 syndromes show abnormalities in p63, each syndrome tends to demonstrate mutations in specific domains. EEC, orofacial cleft 8, SHFM4, and ADULT syndrome are associated with missense mutations in the DNA binding domain. In contrast, mutations in the sterile alpha motif / transcription inhibitory domain (SAM/TID), which is downstream of the DNA binding domain, result in AEC syndrome phenotypes. Missense mutations in between the transactivation domain and DNA binding domain or truncation of the SAM/TID are typical of limb-mammary syndrome.

For more information on EEC, see OMIM.

Codes

ICD10CM:
Q89.8 – Other specified congenital malformations

SNOMEDCT:
39788007 – Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome

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Differential Diagnosis & Pitfalls

  • AEC syndrome – Scalp erosions, ankyloblepharon.
  • Limb-mammary syndrome – No skin or hair abnormalities, breast and nipple hypoplasia.
  • SHFM4 syndrome – Ectrodactyly exclusively.
  • Orofacial cleft 8 syndrome – Isolated cleft lip / palate.
  • Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome – Ectrodactyly and ectodermal dysplasia but without palatal clefting.
  • Anhidrotic / hypohidrotic ectodermal dysplasia – Patients present with hypohidrosis or anhidrosis, hypodontia or anodontia, and hypotrichosis. Nails are usually normal. Patients often have significant atopic dermatitis. 
  • Hidrotic ectodermal dysplasia – Patients are often of French-Canadian ancestry and have a mutation in connexin 30 (GJB6). They present with thin brittle hair, symmetric hyperkeratosis of palms / soles, and micronychia, often with milky-white nail plates. Normal sweating and dentition. No clefting.
  • Odontotrichomelic syndrome – Severe limb deformities.
  • Adams-Oliver syndrome – No clefting but with limb abnormalities.
  • Curly hair-ankyloblepharon-nail dysplasia (CHANDS) syndrome
  • Congenital ichthyosis
  • Witkop (tooth and nail syndrome) – Koilonychias; secondary teeth fail to erupt. No other dermatologic features.

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References

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Last Reviewed: 03/21/2018
Last Updated: 04/20/2018
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Ectrodactyly-ectodermal dysplasia-clefting syndrome
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Ectrodactyly-ectodermal dysplasia-clefting syndrome : Sparse body hair, Sparse eyebrows, Hypohidrosis, Teeth abnormalities, Dry eyes
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