| DISEASE ASSOCIATIONS |
CHARACTERIZATION |
| ACANTHOSIS NIGRICANS |
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Autosomal dominant ectodermal dysplasia.
Jorgenson RJ, Dowben JS, Dowben SL.
Department of Pediatric Dentistry, University of Texas Health Science Center, San Antonio 78284.
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| J Craniofac Genet Dev Biol. 1987;7(4):403-12. Abstract quote |
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A three generation family with hypohidrotic ectodermal dysplasia (ED) is presented. Attempts to categorize the disorder in the family as one of the recognized types of ED were unsuccessful.
Affected members of the family have mild hypotrichosis, mild hypodontia, and variable degrees of hypohidrosis. Autosomal dominant inheritance is proposed. Scanning electron microscopy on the hair of members of the family is presented.
While there is no specific pattern of defects of the hair of affected persons, the cuticular layer is defective and there are longitudinal grooves in the hair shafts.
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| HYPOTHYROIDISM |
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Hypohidrotic ectodermal dysplasia with hypothyroidism.
Pabst HF, Groth O, McCoy EE.
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| J Pediatr. 1981 Feb;98(2):223-7. Abstract quote |
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Two brothers with hypohidrotic ectodermal dysplasia were found to have urticaria pigmentosa-like skin pigmentation with increased mast cells and melanin depositions in the dermis. Structural ciliary abnormalities of the respiratory tract were seen, and these may contribute to their severe recurrent chest infections.
Primary hypothyroidism occurred in both by 3 years of age and responded to replacement therapy. The abnormalities seen appear to be the result of a common genetic aberration causing a particular sequence of maldevelopments during embryogenesis.
This form of hypohidrotic ectodermal dysplasia associated with hypothyroidism gives a unique insight into the potential extent of structural defects of ectodermal dysplasias.
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| TRACHEAL CANCER |
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Hypohidrotic ectodermal dysplasia associated with squamous cell carcinoma of the trachea.
Winter SC, Bates GJ.
Department of Otolaryngology, Radcliffe Infirmary, Oxford, UK.
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| J Laryngol Otol. 2002 Sep;116(9):742-3. Abstract quote |
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Hypohidrotic ectodermal dysplasia (HED) is a rare condition characterized by abnormalities to ectodermal derived tissues although other organs or systems are frequently involved. Patients with HED can have a number of symptoms that may lead them to present to the otolaryngologist.
We present a case of a 37-year-old female with HED who initially presented with nasal obstruction but then very rapidly developed stridor due to a tracheal squamous cell carcinoma.
We suggest a possible association between HED and carcinoma of the upper respiratory tract that has not previously been reported.
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| PATHOGENESIS |
CHARACTERIZATION |
| APOPTOSIS |
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Induction of apoptosis by X-linked ectodermal dysplasia receptor via a caspase 8-dependent mechanism.
Sinha SK, Chaudhary PM.
Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX 75390-8593.
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| J Biol Chem. 2004 Jul 26 Abstract quote |
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XEDAR is a recently isolated member of the Tumor Necrosis Factor Receptor (TNFR) family that is highly expressed during embryonic development and binds to ectodysplasin-A2 (EDA-A2).
In this report, we demonstrate that although XEDAR lacks a death domain, it nevertheless induces apoptosis in an EDA-A2-dependent fashion. The apoptosis-inducing ability of XEDAR is dependent on the activation of caspase 8 and can be blocked by its genetic and pharmacological inhibitors. Although XEDAR-induced apoptosis can be blocked by dominant-negative FADD and FADD siRNA, XEDAR does not directly bind to FADD, TRADD or RIP1. Instead, XEDAR signaling leads to the formation of a secondary complex containing FADD, caspase 8 and caspase 10, which results in caspase activation. Thus, XEDAR belongs to a novel class of death receptors that lack a discernible death domain but are capable of activating apoptosis in caspase 8 and FADD-dependent fashion.
XEDAR may represent an early stage in the evolution of death receptors prior to the emergence of death domain and may play a role in the induction of apoptosis during embryonic development and adult life.
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| GENETIC DEFECTS |
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A novel missense mutation (402C-->T) in exon 1 in the EDA gene in a family with X-linked hypohidrotic ectodermal dysplasia.
Hertz JM, Norgaard Hansen K, Juncker I, Kjeldsen M, Gregersen N.
Department of Clinical Genetics, Aarhus University Hospital, Denmark.
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| Clin Genet. 1998 Mar;53(3):205-9. Abstract quote |
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Hypohidrotic ectodermal dysplasia (EDA), or Christ-Siemens-Touraine syndrome, is clinically characterized by hypohidrosis, hypoodontia and hypotrichosis. The X-linked form of the disease has been mapped to Xq12-q13.1, and a gene from this region has recently been cloned.
This gene encodes a predicted transmembrane protein of 135 amino acids, which was found to be expressed in keratinocytes, hair follicles, and sweat glands. A variety of rearrangements in this gene have been found in patients with hypohidrotic ectodermal dysplasia.
We have screened the probands from nine unrelated Danish families with hypohidrotic ectodermal dysplasia for mutation in exon 1 of the EDA-gene by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). In one large kindred we identified a novel missense mutation (402C-->T), which changes a histidine to tyrosine at position 54 in the protein.
This mutation cosegregates with the disease in the family and is the first mutation described which affects the predicted transmembrane, hydrophobic domain of the protein.
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Possible genetic heterogeneity in X linked hypohidrotic ectodermal dysplasia.
Goodship J, Malcolm S, Clarke A, Pembrey ME.
Department of Child Health, Medical School, Newcastle upon Tyne.
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| J Med Genet. 1990 Jul;27(7):422-5. Abstract quote |
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Hypohidrotic ectodermal dysplasia has been mapped to Xq11-q13 by linkage studies and by a translocation in a manifesting female.
We report a family with hypohidrotic ectodermal dysplasia in which the disease did not segregate with this region of the X chromosome as expected. Ten DNA probes which are localised between Xp11 and Xq22 were used in the investigation.
The difficulties in diagnosing the carrier state in this condition and the possibility of non-allelic heterogeneity are discussed.
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GROSS APPEARANCE/
CLINICAL
VARIANTS |
CHARACTERIZATION |
| GENERAL |
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Ectodermal dysplasia: literature review and a case report.
Tape MW, Tye E.
University of Texas, Houston, USA.
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| Compend Contin Educ Dent. 1995 May;16(5):524-8. Abstract quote |
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Ectodermal dysplasia is a group of rare inherited disorders that affect various tissues of ectodermal origin. The mode of inheritance varies among the different disorders.
The most common form of ectodermal dysplasia is hypohidrotic ectodermal dysplasia (HED), which most severely affects the hair, nails, teeth, and skin. Men are more often and more severely affected than women. However, transmission is from the female carrier, who usually appears normal and unaffected. Dental treatment for these patients varies on an individual basis.
This article illustrates a case of overdentures in a 7-year-old boy with HED.
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| AUTOSOMAL DOMINANT |
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Autosomal dominant hypohidrotic ectodermal dysplasia in a large family.
Aswegan AL, Josephson KD, Mowbray R, Pauli RM, Spritz RA, Williams MS.
Gunderson Medical Foundation, La Crosse, Wisconsin, USA.
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| Am J Med Genet. 1997 Nov 12;72(4):462-7. Abstract quote |
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We have studied an autosomal dominant hypohidrotic ectodermal dysplasia in 38 individuals over six generations in one family.
Thirty-two affected individuals in four generations are still living. Questionnaire responses were received from 21 of the affected relatives and some of the individuals were examined by one of the authors.
Smooth, dry, thin skin is seen in most affected individuals. Nearly all have fine, slow-growing scalp and body hair and all have sparse eyebrows and short eyelashes. Nearly all show a decrease in sweating, with some only sweating under the arms and/or on the palms and soles. All affected individuals lacked some deciduous teeth and some permanent teeth. Some teeth are abnormally shaped. Nail abnormalities are more variable and may occur more frequently with increasing age. No other abnormalities are seen in affected individuals in this family.
We reviewed 40 autosomal dominant ectodermal dysplasia syndromes. This family bears some resemblance to a family described by Jorgensen et al. [1987]; however, it appears to represent a disorder that has not been described previously.
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Autosomal dominant ectodermal dysplasia.
Jorgenson RJ, Dowben JS, Dowben SL.
Department of Pediatric Dentistry, University of Texas Health Science Center, San Antonio 78284.
|
-
| J Craniofac Genet Dev Biol. 1987;7(4):403-12. Abstract quote |
|
A three generation family with hypohidrotic ectodermal dysplasia (ED) is presented. Attempts to categorize the disorder in the family as one of the recognized types of ED were unsuccessful.
Affected members of the family have mild hypotrichosis, mild hypodontia, and variable degrees of hypohidrosis. Autosomal dominant inheritance is proposed. Scanning electron microscopy on the hair of members of the family is presented.
While there is no specific pattern of defects of the hair of affected persons, the cuticular layer is defective and there are longitudinal grooves in the hair shafts.
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| DENTAL |
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Dental and craniofacial findings in hypohidrotic ectodermal dysplasia during the primary dentition phase.
Vierucci S, Baccetti T, Tollaro I.
Department of Orthodontics, University of Florence, Italy.
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| J Clin Pediatr Dent. 1994 Summer;18(4):291-7. Abstract quote |
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A more detailed knowledge of dental and craniofacial features in hypohidrotic ectodermal dysplasia (HED) during childhood is needed in order to include these characteristics among diagnostic criteria. The present study comprised 5 HED children, 4 males and 1 female, during the primary dentition phase. Clinical and radiological dental findings consisted of multiple congenitally missing primary teeth, conoid primary incisors, moderate to severe taurodontic second primary molars. Supernumerary cusps and diastema were found as well. A pattern of symmetry was assessed for hypodontia in the primary dentition. The cephalometric study compared the HED sample to a matched non-syndrome sample and revealed abnormally short maxillary depth (p < 0.05), strongly reduced lower facial height (p < 0.01) and a reduction in facial soft tissue thickness (p < 0.05 - p < 0.01) in HED children. The importance of an early diagnosis and treatment of HED dento-facial malformations so as to improve esthetics and function is stressed.
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| FOCAL PALMOPLANTAR AND GINGIVAL KERATOSIS |
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Focal palmoplantar and gingival keratosis: a distinct palmoplantar ectodermal dysplasia with epidermolytic alterations but lack of mutations in known keratins.
Kolde G, Hennies HC, Bethke G, Reichart PA.
Departments of Dermatology and Allergy, Charite-University Medicine of Berlin, Schumannstr. 20/21, 10117 Berlin/Germany.
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| J Am Acad Dermatol. 2005 Mar;52(3 Pt 1):403-9. Abstract quote |
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Focal palmoplantar and gingival keratosis is a rare autosomal dominant disease whose clinical features, and in particular, pathologic alterations and molecular etiology remain to be well defined.
Recently we observed a German family affected by the disease in at least 3 consecutive generations. The 4 patients examined showed circumscribed and painful hyperkeratosis at the weight-bearing plantar skin since infancy, rather mild palmar hyperkeratosis, and continuous leukokeratosis confined to the maxillary and mandibulary attached gingiva. There were no nail changes, subungeal keratoses, or follicular hyperkeratosis. Light and electron microscopy of the plantar and gingival lesions revealed alterations of epidermolytic hyperkeratosis. Mutations in the known keratin genes were excluded by linkage analysis using microsatellite markers.
We conclude that focal palmoplantar and gingival keratosis is a clinically distinct palmoplantar ectodermal dysplasia that is pathologically characterized by epidermolytic alterations, but is most probably not caused by a mutation in a keratin gene.
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| HYPOTRICHOSIS AND NAIL DYSPLASIA |
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Hypotrichosis and nail dysplasia: a novel hidrotic ectodermal dysplasia.
Harrison S, Sinclair R.
Department of Medicine (Dermatology), St Vincent's Hospital, Fitzroy, Melbourne, Victoria 5065, Australia.
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| Australas J Dermatol. 2004 May;45(2):103-5. Abstract quote |
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We report a unique isolated hair and nail ectodermal dysplasia in a 3-year-old girl. Clinical examination revealed short, sparse scalp hair, absent eyebrows, short eyelashes and nail dystrophy in all digits.
Nail changes included shortened nail plate with distal onycholysis and loss of the cuticle. Sweating and teeth were normal. Development was normal. Scanning electron microscopy of the hair only demonstrated trichorrhexis nodosa. There was no pili torti. Vertically sectioned scalp biopsy revealed hypoplastic hair follicles and a horizontally sectioned biopsy showed a decrease in the overall number of hair follicles present.
Treatment with topical minoxidil 5% 1 mL twice each day massaged into the scalp led to only minimal improvement and was discontinued after 12 months.
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| RAPP-HODGKIN SYNDROME |
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Rapp-Hodgkin syndrome: an ectodermal dysplasia involving the teeth, hair, nails, and palate. Report of a case and review of the literature.
Crawford PJ, Aldred MJ, Clarke A, Tso MS.
Department of Child Dental Health, University of Wales College of Medicine, Cardiff, United Kingdom.
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| Oral Surg Oral Med Oral Pathol. 1989 Jan;67(1):50-62. Abstract quote |
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Rapp-Hodgkin syndrome is a rare form of ectodermal dysplasia involving the hair, eyes, sweat glands, nails, teeth, and palate.
The case of a white girl with the condition is presented. The differential diagnosis is discussed, and the eight previously reported cases are reviewed.
Another (ninth) previously reported case is considered for inclusion in the group.
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| HISTOLOGICAL TYPES |
CHARACTERIZATION |
| GENERAL |
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| SKIN |
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Hair and sweat glands in families with hypohidrotic ectodermal dysplasia: further characterization.
Rouse C, Siegfried E, Breer W, Nahass G.
Department of Dermatology, Saint Louis University, 1034 S. Brentwood Road, St Louis, MO 63117, USA.
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| Arch Dermatol. 2004 Jul;140(7):850-5. Abstract quote |
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OBJECTIVES: To gather and compare clinical and histologic information from individuals affected by hypohidrotic ectodermal dysplasia (HED) and unaffected control subjects and to assess the value of these data in the diagnosis of HED.
DESIGN: Volunteer subjects attending the 20th Annual Family Conference of the National Foundation for Ectodermal Dysplasia answered a questionnaire and performed a starch-iodide sweat-function test. A subset of the subjects also donated samples of hair and 4-mm punch biopsy specimens of palmar and scalp skin. Specimens from each of these tests were assessed in a blinded fashion. Analysis was performed comparing affected and control subjects for each of the following parameters: quantification of eccrine structures in the skin biopsy specimens, analysis of hair sample trichograms for hair shaft defects, and qualitative classification of starch-iodide palm-print sweat-function test results.
SETTING: An international conference for families and individuals with ectodermal dysplasias.
SUBJECTS: A total of 40 subjects were included in the final analysis: 15 unaffected control subjects and 25 subjects with HED. Nine affected subjects and 9 unaffected subjects donated skin biopsy specimens.
MAIN OUTCOME MEASURE: This study was designed to assess the value of 4 simple tests in supporting the diagnosis of HED.
RESULTS: Investigators were blinded to group during analysis of the test samples. Trichogram examination identified 3 hair shaft abnormalities, with a slightly higher prevalence in the affected group: variable shaft thickness, trichorrhexis nodosa, and pili torti. The sensitivity and specificity for each of these findings was less than 40%. Starch-iodide paper palm imprints identified a higher likelihood of diminished or absent sweat in the affected group, but this test had a low sensitivity (44%) and an imperfect specificity (93%). Examination of horizontally sectioned skin biopsy specimens from the palm were devoid of eccrine structures in a minority of affected subjects (sensitivity, 30%; specificity, 100%). In contrast, scalp biopsy specimens lacked eccrine structures in the majority of affected subjects (sensitivity, 67%; specificity, 100%). Separate analysis excluding the subjects without apparent eccrine apparatus yielded comparable numbers of eccrine ducts from control and affected groups.
CONCLUSIONS: We have defined the value of simple, easily performed tests in the morphological diagnosis of HED. Noninvasive trichogram and sweat testing results can support the diagnosis of HED, but they are not sensitive or highly specific; horizontally sectioned 4-mm punch biopsy specimens of the scalp or palms that lack eccrine structures are diagnostic of HED; scalp biopsy is much more sensitive than palmar biopsy; and a scalp biopsy specimen with detectable eccrine structures suggests that a patient does not have HED.
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SPECIAL STAINS/
IMMUNOHISTO-CHEMISTRY |
CHARACTERIZATION |
| ELECTRON MICROSCOPY |
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Histopathological and ultrastructural study of ectodermal dysplasia/skin fragility syndrome.
Bergman R, Sprecher E.
From The Department of Dermatology, Rambam Medical Center and the Bruce Rappaport Faculty of Medicine, Technion-Israel, Institute of Technology, Haifa, Israel.
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| Am J Dermatopathol. 2005 Aug;27(4):333-8. Abstract quote |
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Ectodermal dysplasia/skin fragility syndrome (EDSFS) (MIM604536) is a newly described autosomal recessive disorder characterized by skin fragility and blistering, palmoplantar keratoderma, abnormal hair growth, nail dystrophy, and occasionally defective sweating. It results from mutations in the PKP1 gene encoding plakophilin 1 (PKP1), which is an important component of stratifying epithelial desmosomes and a nuclear component of many cell types.
Our study was performed to further characterize the histopathology of EDSFS in different cutaneous sites with a special emphasis on the hypotrichosis and keratoderma. A total of 4 biopsies were obtained from 2 EDSFS female patients, aged 9 days to 4 years. The biopsies were taken from the blistering skin of the leg and trunk, the hyperkeratotic skin of the sole, and the hypotrichotic scalp. The observed histopathologic features included: widened intercellular spaces, suprabasal intraepidermal clefts and blisters with acantholytic keratinocytes, detachments of the upper epidermal layers due to disadhesion, varying degrees of dyskeratosis that were much more pronounced in the plantar hyperkeratotic skin, and increased number of catagen-telogen hair follicles. The electron-microscopic observations attributed the disadhesion and acantholysis to reduced numbers of small hypoplastic desmosomes, and the dyskeratosis to the detachment of intracellular keratin filaments from the desmosomes with perinuclear condensation, which might also underlie the plantar keratoderma.
The hair follicle findings suggest disturbance in the hair cycle, which might be attributed to disturbed nuclear PKP1 function or result from aberrant desmosomal signaling.
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| TREATMENT |
CHARACTERIZATION |
| GENERAL |
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Pure ectodermal dysplasia: retrospective study of 16 cases and literature review.
Ruhin B, Martinot V, Lafforgue P, Catteau B, Manouvrier-Hanu S, Ferri J.
Department of Oral and Maxillofacial Surgery, Roger Salengro University Hospital, Boulevard du Professeur Leclercq, 59037 Lille Cedex, France.
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| Cleft Palate Craniofac J. 2001 Sep;38(5):504-18. Abstract quote |
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OBJECTIVE: To review the possible craniomaxillofacial deformative consequences associated with ectodermal dysplasias and embryonic malformations, which include dental ageneses.
SETTING: Oral and Maxillofacial Surgery Department, University Hospital, Lille, France.
PATIENTS: Sixteen patients (seven boys and nine girls, aged 4 to 34 years) with pure ectodermal dysplasia (no ectodermal dysplasia syndromes).
INTERVENTIONS: All patients had a clinical examination. Seven (two boys and five girls, aged 4 to 25 years) had undergone plaster casts and radiographic and Delaire's cephalometric studies before being treated.
MAIN OUTCOME MEASURES: All patients had tooth ageneses (from hypodontia to anodontia), associated with cutaneous dyshidrosis and hair and nail dystrophy. Most of them had a short face, with an unusual facial concavity, a maxillary retrusion, and a relative mandibular protrusion.
MANAGEMENT RESULTS AND DISCUSSION: Depending on their ages and their orthopedic abnormalities, patients underwent either dental or prosthodontic, orthodontic, orthopedic, orthognathic, or implant treatment. So as not to interfere with the growth pattern, we preferred to reserve implant and orthognathic surgery for full-grown cases.
CONCLUSIONS: Oral and maxillofacial surgeons must undertake a comprehensive approach to these patients to improve their dental, masticatory, growing, and orthognathic conditions.
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| DENTAL |
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Orthodontic and prosthodontic treatment of ectodermal dysplasia--a case report.
Yenisey M, Guler A, Unal U.
Ondokuz Mayis University, Faculty of Dentistry, 55139 Kurupelit-Samsun, Turkey. |
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| Br Dent J. 2004 Jun 12;196(11):677-9. Abstract quote |
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In addition to its other symptoms, ectodermal dysplasia causes anodontia and hypodontia intraorally. Partial or total anodontia results in some loss of function, such as chewing, and affects aesthetics. Prosthodontic rehabilitation can be accomplished with fixed, overdenture, complete, or implant-retained prostheses.
For rehabilitation, it is crucial to know the age, number and condition of present teeth, and the state of growth of the patient. A 10-year-old male patient who visited our clinic was treated by a multi-disciplinary team of surgeons, orthodontists, and prosthodontists. An overdenture was planned, and an implant-supported prosthesis was considered for when the patient had finished growing.
A clasp retained over the denture was planned for prosthetic rehabilitation after considering his growth and the number and condition of his present teeth.
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