Laboratory Studies

In general, laboratory studies are not useful in the diagnosis or management of the ectodermal dysplasias.

Patients with ectodermal dysplasia associated with immunodeficiency may have hypogammaglobulinemia with impaired lymphocyte proliferation and cell-mediated immunity. An appropriate evaluation, including determination of quantitative immunoglobulin levels and T-cell subset populations, should be performed.

Imaging Studies

Perform orthopantography at an early age if hypodontia or dental abnormalities are present.

X-ray films of hands, feet, or both may demonstrate specific skeletal deformities.

Renal ultrasonography, voiding cystourethrography, and intravenous pyelography may be helpful in evaluating children with ectodermal dysplasia in association with cleft lip and/or palate for underlying genitourinary tract anomalies.

Other Tests

Sweat pore counts, pilocarpine iontophoresis, and skin biopsy may document hypohidrosis and a reduction in the number of eccrine glands.

Sweat pore counts may be performed using yellow starch–iodine powder applied to palmar or dorsal skin. In unaffected persons, sweating turns the yellow starch–iodine powder to deep purple, allowing visualization of sweat pores. Sweat pores are poorly visualized in affected children. Female carriers of X-linked EDA may demonstrate a mosaic pattern of areas of normal numbers of sweat pores alternating with areas of absent pores. Streaky areas of hypohidrosis that follow Blaschko lines are observed upon starch-iodine staining.

For skin biopsy, the hypothenar eminence is the most reliable biopsy site in order to demonstrate an absence or hypoplasia of sweat glands. Fetal skin biopsy may help identify the presence of decreased numbers of eccrine sweat glands for prenatal diagnosis of hypohidrotic ectodermal dysplasia.

Prenatal diagnosis using genetic mutation analysis may be performed for those ectodermal dysplasias in which the genetic mutation is known.

Indirect prenatal diagnosis may be performed by linkage analysis applied to chorionic villus samples at the 10th week of gestation for some ectodermal dysplasias.

Genetic testing for several forms of ectodermal dysplasia, including hidrotic ectodermal dysplasia; X-linked recessive and autosomal dominant hypohidrotic ectodermal dysplasia; EEC syndrome, AEC syndrome, and other related ectodermal dysplasias and WNT10A-associated ectodermal dysplasias is available through GeneDx.

Histologic Findings

Skin histopathology documents a reduction in the number of sweat glands, hair follicles, and sebaceous glands associated with the different ectodermal dysplasias. In EDA, the epidermis is thin and flattened. Eccrine sweat glands are few or poorly developed or are very rudimentary. Beyond the skin, mucous glands in the upper respiratory tract and bronchi are often reduced in number. Salivary glands may show ectasia of ducts and inflammatory changes.

Treatment & Management

Weech AA. Hereditary ectodermal dysplasia (congenital ectodermal defect). Am J Dis Child. 1929. 37:766-90.
Pinheiro M, Freire-Maia N. The ectodermal dysplasias. Arch Dermatol. 1982 Apr. 118(4):215-6. [QxMD MEDLINE Link].
Pinheiro M, Freire-Maia N. Ectodermal dysplasias: a clinical classification and a causal review. Am J Med Genet. 1994 Nov 1. 53(2):153-62. [QxMD MEDLINE Link].
Freire-Maia N, Lisboa-Costa T, Pagnan NA. Ectodermal dysplasias: how many?. Am J Med Genet. 2001 Nov 15. 104(1):84. [QxMD MEDLINE Link].
Visinoni AF, Lisboa-Costa T, Pagnan NA, Chautard-Freire-Maia EA. Ectodermal dysplasias: clinical and molecular review. Am J Med Genet A. 2009 Sep. 149A(9):1980-2002. [QxMD MEDLINE Link].
Pagnan NA, Visinoni ÁF. Update on ectodermal dysplasias clinical classification. Am J Med Genet A. 2014 Oct. 164A (10):2415-23. [QxMD MEDLINE Link].
Lamartine J. Towards a new classification of ectodermal dysplasias. Clin Exp Dermatol. 2003 Jul. 28(4):351-5. [QxMD MEDLINE Link].
Priolo M, Lagana C. Ectodermal dysplasias: a new clinical-genetic classification. J Med Genet. 2001 Sep. 38(9):579-85. [QxMD MEDLINE Link].
Itin PH, Fistarol SK. Ectodermal dysplasias. Am J Med Genet C Semin Med Genet. 2004 Nov 15. 131C(1):45-51. [QxMD MEDLINE Link].
Okamura E, Suda N, Baba Y, Fukuoka H, Ogawa T, Ohkuma M, et al. Dental and maxillofacial characteristics in six Japanese individuals with ectrodactyly-ectodermal dysplasia-clefting (EEC)syndrome. Cleft Palate Craniofac J. 2012 Jan 11. [QxMD MEDLINE Link].
Rouse C, Siegfried E, Breer W, Nahass G. Hair and sweat glands in families with hypohidrotic ectodermal dysplasia: further characterization. Arch Dermatol. 2004 Jul. 140(7):850-5. [QxMD MEDLINE Link].
Berg D, Weingold DH, Abson KG, Olsen EA. Sweating in ectodermal dysplasia syndromes. A review. Arch Dermatol. 1990 Aug. 126(8):1075-9. [QxMD MEDLINE Link].
Clauss F, Maniere MC, Obry F, et al. Dento-craniofacial phenotypes and underlying molecular mechanisms in hypohidrotic ectodermal dysplasia (HED): a review. J Dent Res. 2008 Dec. 87(12):1089-99. [QxMD MEDLINE Link].
Priolo M. Ectodermal dysplasias: an overview and update of clinical and molecular-functional mechanisms. Am J Med Genet A. 2009 Sep. 149A(9):2003-13. [QxMD MEDLINE Link].
Kere J, Srivastava AK, Montonen O, et al. X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein. Nat Genet. 1996 Aug. 13(4):409-16. [QxMD MEDLINE Link].
Monreal AW, Zonana J, Ferguson B. Identification of a new splice form of the EDA1 gene permits detection of nearly all X-linked hypohidrotic ectodermal dysplasia mutations [published erratum appears in Am J Hum Genet 1998 Oct;63(4):1253-5]. Am J Hum Genet. 1998 Aug. 63(2):380-9. [QxMD MEDLINE Link].
Jones KB, Goodwin AF, Landan M, Seidel K, Tran DK, Hogue J, et al. Characterization of X-linked hypohidrotic ectodermal dysplasia (XL-HED) hair and sweat gland phenotypes using phototrichogram analysis and live confocal imaging. Am J Med Genet A. 2013 Jul. 161A(7):1585-93. [QxMD MEDLINE Link].
Monreal AW, Ferguson BM, Headon DJ, Street SL, Overbeek PA, Zonana J. Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia. Nat Genet. 1999 Aug. 22(4):366-9. [QxMD MEDLINE Link].
Wisniewski SA, Trzeciak WH. A rare heterozygous TRAF6 variant is associated with hypohidrotic ectodermal dysplasia. Br J Dermatol. 2012 Jun. 166(6):1353-6. [QxMD MEDLINE Link].
Lamartine J, Munhoz Essenfelder G, Kibar Z, et al. Mutations in GJB6 cause hidrotic ectodermal dysplasia. Nat Genet. 2000 Oct. 26(2):142-4. [QxMD MEDLINE Link].
Courtois G, Smahi A, Reichenbach J, et al. A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency. J Clin Invest. 2003 Oct. 112(7):1108-15. [QxMD MEDLINE Link].
Doffinger R, Smahi A, Bessia C, et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet. 2001 Mar. 27(3):277-85. [QxMD MEDLINE Link].
Zonana J, Elder ME, Schneider LC, et al. A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet. 2000 Dec. 67(6):1555-62. [QxMD MEDLINE Link].
Rinne T, Brunner HG, van Bokhoven H. p63-associated disorders. Cell Cycle. 2007 Feb 1. 6(3):262-8. [QxMD MEDLINE Link].
Rinne T, Hamel B, van Bokhoven H, Brunner HG. Pattern of p63 mutations and their phenotypes--update. Am J Med Genet A. 2006 Jul 1. 140(13):1396-406. [QxMD MEDLINE Link].
Richard G, Rouan F, Willoughby CE, et al. Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome. Am J Hum Genet. 2002 May. 70(5):1341-8. [QxMD MEDLINE Link]. [Full Text].
Suzuki K, Hu D, Bustos T, et al. Mutations of PVRL1, encoding a cell-cell adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal dysplasia. Nat Genet. 2000 Aug. 25(4):427-30. [QxMD MEDLINE Link].
McGrath JA, McMillan JR, Shemanko CS, et al. Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome. Nat Genet. 1997 Oct. 17(2):240-4. [QxMD MEDLINE Link].
Wang X, Reid Sutton V, Omar Peraza-Llanes J, et al. Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia. Nat Genet. 2007 Jul. 39(7):836-8. [QxMD MEDLINE Link].
Lugassy J, Itin P, Ishida-Yamamoto A, et al. Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14. Am J Hum Genet. 2006 Oct. 79(4):724-30. [QxMD MEDLINE Link].
Shah S, Boen M, Kenner-Bell B, Schwartz M, Rademaker A, Paller AS. Pachyonychia congenita in pediatric patients: natural history, features, and impact. JAMA Dermatol. 2014 Feb. 150 (2):146-53. [QxMD MEDLINE Link].
Wilson NJ, O'Toole EA, Milstone LM, Hansen CD, Shepherd AA, Al-Asadi E, et al. The molecular genetic analysis of the expanding pachyonychia congenita case collection. Br J Dermatol. 2014 Aug. 171 (2):343-55. [QxMD MEDLINE Link].
McLean WH, Hansen CD, Eliason MJ, Smith FJ. The phenotypic and molecular genetic features of pachyonychia congenita. J Invest Dermatol. 2011 May. 131 (5):1015-7. [QxMD MEDLINE Link].
Galdzicka M, Patnala S, Hirshman MG, et al. A new gene, EVC2, is mutated in Ellis-van Creveld syndrome. Mol Genet Metab. 2002 Dec. 77(4):291-5. [QxMD MEDLINE Link].
Ruiz-Perez VL, Ide SE, Strom TM, et al. Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis. Nat Genet. 2000 Mar. 24(3):283-6. [QxMD MEDLINE Link].
Ruiz-Perez VL, Tompson SW, Blair HJ, et al. Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome. Am J Hum Genet. 2003 Mar. 72(3):728-32. [QxMD MEDLINE Link].
Ali RH, Habib R, Ud-Din N, Khan MN, Ansar M, Ahmad W. Novel mutations in the gene HOXC13 underlying pure hair and nail ectodermal dysplasia in consanguineous families. Br J Dermatol. 2013 Aug. 169(2):478-80. [QxMD MEDLINE Link].
Naeem M, Wajid M, Lee K, Leal SM, Ahmad W. A mutation in the hair matrix and cuticle keratin KRTHB5 gene causes ectodermal dysplasia of hair and nail type. J Med Genet. 2006 Mar. 43(3):274-9. [QxMD MEDLINE Link]. [Full Text].
Shimomura Y, Wajid M, Kurban M, Sato N, Christiano AM. Mutations in the keratin 85 (KRT85/hHb5) gene underlie pure hair and nail ectodermal dysplasia. J Invest Dermatol. 2010 Mar. 130(3):892-5. [QxMD MEDLINE Link].
Smahi A, Courtois G, Vabres P, Yamaoka S, Heuertz S, Munnich A, et al. Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature. 2000 May 25. 405(6785):466-72. [QxMD MEDLINE Link].
Lian J, Cuk M, Kahlfuss S, Kozhaya L, Vaeth M, Rieux-Laucat F, et al. ORAI1 mutations abolishing store-operated Ca2+ entry cause anhidrotic ectodermal dysplasia with immunodeficiency. J Allergy Clin Immunol. 2018 Oct. 142 (4):1297-1310.e11. [QxMD MEDLINE Link].
Bohring A, Stamm T, Spaich C, Haase C, Spree K, Hehr U, et al. WNT10A mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes. Am J Hum Genet. 2009 Jul. 85(1):97-105. [QxMD MEDLINE Link]. [Full Text].
Adaimy L, Chouery E, Megarbane H, Mroueh S, Delague V, Nicolas E, et al. Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. Am J Hum Genet. 2007 Oct. 81(4):821-8. [QxMD MEDLINE Link]. [Full Text].
Mues G, Bonds J, Xiang L, Vieira AR, Seymen F, Klein O, et al. The WNT10A gene in ectodermal dysplasias and selective tooth agenesis. Am J Med Genet A. 2014 Oct. 164A (10):2455-60. [QxMD MEDLINE Link].
Tziotzios C, Petrof G, Liu L, Verma A, Wedgeworth EK, Mellerio JE, et al. Clinical features and WNT10A mutations in seven unrelated cases of Schöpf-Schulz-Passarge syndrome. Br J Dermatol. 2014 Nov. 171 (5):1211-4. [QxMD MEDLINE Link].
Motil KJ, Fete TJ, Fraley JK, et al. Growth characteristics of children with ectodermal dysplasia syndromes. Pediatrics. 2005 Aug. 116(2):e229-34. [QxMD MEDLINE Link].
Kaercher T. Ocular symptoms and signs in patients with ectodermal dysplasia syndromes. Graefes Arch Clin Exp Ophthalmol. 2004 Jun. 242(6):495-500. [QxMD MEDLINE Link].
Nordgarden H, Storhaug K, Lyngstadaas SP, Jensen JL. Salivary gland function in persons with ectodermal dysplasias. Eur J Oral Sci. 2003 Oct. 111(5):371-6. [QxMD MEDLINE Link].
Dietz J, Kaercher T, Schneider AT, Zimmermann T, Huttner K, Johnson R, et al. Early respiratory and ocular involvement in X-linked hypohidrotic ectodermal dysplasia. Eur J Pediatr. 2013 Aug. 172(8):1023-31. [QxMD MEDLINE Link].
Daniel E, McCurdy EA, Shashi V, McGuirt WF Jr. Ectodermal dysplasia: otolaryngologic manifestations and management. Laryngoscope. 2002 Jun. 112(6):962-7. [QxMD MEDLINE Link].
Mehta U, Brunworth J, Lewis RA, Sindwani R. Rhinologic manifestations of ectodermal dysplasia. Am J Rhinol. 2007 Jan-Feb. 21(1):55-8. [QxMD MEDLINE Link].
Callea M, Teggi R, Yavuz I, Tadini G, Priolo M, Crovella S, et al. Ear nose throat manifestations in hypoidrotic ectodermal dysplasia. Int J Pediatr Otorhinolaryngol. 2013 Nov. 77(11):1801-4. [QxMD MEDLINE Link].
Bergendal B. Orodental manifestations in ectodermal dysplasia-a review. Am J Med Genet A. 2014 Oct. 164A (10):2465-71. [QxMD MEDLINE Link].
Fete M, Hermann J, Behrens J, Huttner KM. X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry. Am J Med Genet A. 2014 Oct. 164A (10):2437-42. [QxMD MEDLINE Link].
Clouston HR. A hereditary ectodermal dystrophy. Can Med Assoc J. 1929. 21:18-31.
Pierard GE, Van Neste D, Letot B. Hidrotic ectodermal dysplasia. Dermatologica. 1979. 158(3):168-74. [QxMD MEDLINE Link].
Reynold JM, Gold MB, Scriver CR. The characterization of hereditary abnormalities of keratin: Clouston's ectodermal dysplasia. Birth Defects Orig Artic Ser. 1971 Jun. 7(8):91-5. [QxMD MEDLINE Link].
Hay RJ, Wells RS. The syndrome of ankyloblepharon, ectodermal defects and cleft lip and palate: an autosomal dominant condition. Br J Dermatol. 1976 Mar. 94(3):277-89. [QxMD MEDLINE Link].
Fosko SW, Stenn KS, Bolognia JL. Ectodermal dysplasias associated with clefting: significance of scalp dermatitis. J Am Acad Dermatol. 1992 Aug. 27(2 Pt 1):249-56. [QxMD MEDLINE Link].
Roelfsema NM, Cobben JM. The EEC syndrome: a literature study. Clin Dysmorphol. 1996 Apr. 5(2):115-27. [QxMD MEDLINE Link].
Giampietro PF, Baker MW, Basehore MJ, Jones JR, Seroogy CM. Novel mutation in TP63 associated with ectrodactyly ectodermal dysplasia and clefting syndrome and T cell lymphopenia. Am J Med Genet A. 2013 Jun. 161A(6):1432-5. [QxMD MEDLINE Link].
Felding IB, Bjorklund LJ. Rapp-Hodgkin ectodermal dysplasia. Pediatr Dermatol. 1990 Jun. 7(2):126-31. [QxMD MEDLINE Link].
Klineberg I, Cameron A, Hobkirk J, Bergendal B, Maniere MC, King N, et al. Rehabilitation of children with ectodermal dysplasia. Part 2: an international consensus meeting. Int J Oral Maxillofac Implants. 2013 Jul-Aug. 28(4):1101-9. [QxMD MEDLINE Link].
Klineberg I, Cameron A, Whittle T, Hobkirk J, Bergendal B, Maniere MC, et al. Rehabilitation of children with ectodermal dysplasia. Part 1: an international Delphi study. Int J Oral Maxillofac Implants. 2013 Jul-Aug. 28(4):1090-100. [QxMD MEDLINE Link].
Hickey AJ, Vergo TJ. Prosthetic treatments for patients with ectodermal dysplasia. J Prosthet Dent. 2001 Oct. 86(4):364-8. [QxMD MEDLINE Link].
Imirzalioglu P, Uckan S, Haydar SG. Surgical and prosthodontic treatment alternatives for children and adolescents with ectodermal dysplasia: a clinical report. J Prosthet Dent. 2002 Dec. 88(6):569-72. [QxMD MEDLINE Link].
Dhanrajani PJ, Jiffry AO. Management of ectodermal dysplasia: a literature review. Dent Update. 1998 Mar. 25(2):73-5. [QxMD MEDLINE Link].
Lypka M, Yarmand D, Burstein J, Tso V, Yamashita DD. Dental implant reconstruction in a patient with ectodermal dysplasia using multiple bone grafting techniques. J Oral Maxillofac Surg. 2008 Jun. 66(6):1241-4. [QxMD MEDLINE Link].
Tarjan I, Gabris K, Rozsa N. Early prosthetic treatment of patients with ectodermal dysplasia: a clinical report. J Prosthet Dent. 2005 May. 93(5):419-24. [QxMD MEDLINE Link].
Al-Ibrahim HA, Al-Hadlaq SM, Abduljabbar TS, Al-Hamdan KS, Abdin HA. Surgical and implant-supported fixed prosthetic treatment of a patient with ectodermal dysplasia: a case report. Spec Care Dentist. 2012 Jan. 32(1):1-5. [QxMD MEDLINE Link].
El Osta Chaiban R, Chaiban W. Ectodermal dysplasia: dental management and benefits, a case report. Eur J Paediatr Dent. 2011 Dec. 12(4):282-4. [QxMD MEDLINE Link].
Aydinbelge M, Gumus HO, Sekerci AE, Demetoglu U, Etoz OA. Implants in children with hypohidrotic ectodermal dysplasia: an alternative approach to esthetic management: case report and review of the literature. Pediatr Dent. 2013 Sep-Oct. 35(5):441-6. [QxMD MEDLINE Link].
Dhima M, Salinas TJ, Cofer SA, Rieck KL. Rehabilitation of medically complex ectodermal dysplasia with novel surgical and prosthodontic protocols. Int J Oral Maxillofac Surg. 2013 Sep 12. [QxMD MEDLINE Link].
Lee HE, Chang IK, Im M, Seo YJ, Lee JH, Lee Y. Topical minoxidil treatment for congenital alopecia in hypohidrotic ectodermal dysplasia. J Am Acad Dermatol. 2013 Apr. 68(4):e139-40. [QxMD MEDLINE Link].
Melkote S, Dhurat RS, Palav A, Jerajani HR. Alopecia in congenital hidrotic ectodermal dysplasia responding to treatment with a combination of topical minoxidil and tretinoin. Int J Dermatol. 2009 Feb. 48(2):184-5. [QxMD MEDLINE Link].
Theiler M, Frieden IJ. High-Potency Topical Steroids: An Effective Therapy for Chronic Scalp Inflammation in Rapp-Hodgkin Ectodermal Dysplasia. Pediatr Dermatol. 2016 Mar-Apr. 33 (2):e84-7. [QxMD MEDLINE Link].
Dupuis-Girod S, Cancrini C, Le Deist F, et al. Successful allogeneic hemopoietic stem cell transplantation in a child who had anhidrotic ectodermal dysplasia with immunodeficiency. Pediatrics. 2006 Jul. 118(1):e205-11. [QxMD MEDLINE Link].
Fish JD, Duerst RE, Gelfand EW, Orange JS, Bunin N. Challenges in the use of allogeneic hematopoietic SCT for ectodermal dysplasia with immune deficiency. Bone Marrow Transplant. 2008 Sep 15. [QxMD MEDLINE Link].
Schneider H, Faschingbauer F, Schuepbach-Mallepell S, Körber I, Wohlfart S, Dick A, et al. Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia. N Engl J Med. 2018 Apr 26. 378 (17):1604-1610. [QxMD MEDLINE Link].

Media Gallery

A newborn boy with anhidrotic/hypohidrotic ectodermal dysplasia syndrome showing generalized fine scaling and a history of intermittent fever.
Wrinkled, hyperpigmented skin around the eyes and everted lips are typical characteristics of anhidrotic/hypohidrotic ectodermal dysplasia syndrome.
Typical cleft lip/palate and maxillary hyperplasia in a patient with Rapp-Hodgkin syndrome.
Abnormal hair shaft showing pili torti and a longitudinal groove (pili canaliculi) from a patient with Rapp-Hodgkin syndrome.
Hands of father and son with Rapp-Hodgkin syndrome. Nails have the same characteristics; they are brittle, thin, and dystrophic.
Ectodermal dysplasia, ectrodactyly, and clefting syndrome. Light-colored hair and scalp and earlobe defects are observed. Cleft lip and palate results in a characteristic nasal contour.
Ectrodactyly observed in an individual with ectodermal dysplasia, ectrodactyly, and clefting syndrome.