Group+3

Group 3 Members: Nicole, Evan, Michael e-Facilitator: Cathy


 * __Purpose__**
 * discuss the etiology and incidence of Ectodermal Dysplasia (ED)
 * describe the clinical appearance and physiological consequences of ED affected tissues
 * provide a detailed discussion on the possible effects of ED on oral tissues; include how these effects are treated or managed.


 * Ectodermal Dysplasia **


 * __Contents:__**
 * Definition
 * Ectodermal Dysplasia
 * Background into ectodermal development
 * Incidence of ectodermal Dysplasia
 * Manifestations of ED
 * Causes and inheritance patterns
 * Clinical Appearance
 * Diagnosis
 * Physiological consequences
 * Implications
 * Treatment
 * Managment within the dental clinic


 * __Definition:__** The common embryologic neural origin of the ectoderm includes the eipdermal layer of the skin and the amelodentinal (the enamel and dentine) components of the teeth that result in a variety of conditions affecting both skin and dentition. The diseases derived from these components and neuroectodermal mesenchyme are named 'neurocristopathies," signifying any disease arising from maldevelopment of the neural crest (Barankin et al 2009). Ectodermal Dysplasia (ED) is a general term representing a group of inherited disorders characterized by developmental defects in the tissues of the embryonic ectoderm and its appendages, including hair, nails, teeth, nerve (neural) cells, sweat glands and parts of the eye and ear (I.P. Sweeney et al 2005).


 * __Ectodermal Dysplasia-__** First discovered and described by Charles Darwin in 1875 (Bissonette 2006), ED is commonly thought of as one disease, but is defined by the Ectodermal Dysplasia society (2009) as, "a group of closely related conditions of which more than 150 different syndromes have been identified." There is currently no cure for ectodermal dysplasia, and it is often only able to be diagnosed in very few cases, so treatment by a variety of professionals including doctors, dentists and therapists is used to try and create the best possible quality of life for these patients (National Foundation for Ectodermal Dysplasia 2009).


 * __Background__:** The four primary tissues that make up the body organs originate from the three primary germ layers that form during embryonic devlopment. The ectoderm, mesoderm and endoderm sit on top of each other, with the ectodermal layer being most superficial. The development of these these layers is one of the first events to occur in embryonic development and occurs from about the second week of pregnancy until about the eigth week when the major organs are in place (Marieb.E, Hoehn.K, 2007). Figure 4.14 shows a diagram of the embryonic layers with the ectoderm being the blue layer, the mesoderm being the red and the endoderm being the orange layer.

The ectoderm is responsible for the development of the teeth, hair, sweat glands, skin and nails. With ectodermal dysplasia, these ectodermal structures are the ones that are affected and are noted clinically. These structures form from the ectodermal layers during embryonic development and so when a mutation occurs in a gene for the ectodermal development (as described below), this will also cause abnormal development or no development of these structures.

__**Incidence-**__ The current incidence of ED unknown, but a higher incidence has been reported in the French Canadian population (Clouston 1929). ED however still occurs in all races and ethnicities. Also a document published in 1990 stated that about 7 in 10,000 babies are diagnosed with ectodermal dysplasia each year (National Foundation for Ectodermal Dysplaisa 2009).

Absence of Dermal Ridge Patterns, Onychodystrophy, and Palmoplantar Anhidrosis, Acrorenal-Ectodermal Dysplasia-Lipoatrophic Diabetes(AREDYLD)Syndrome, Agammaglobulinemia-Dwarfism-Ectodermal Dysplasia, Agammaglobulinemia-Thymic Dysplasia-Ectodermal Dysplasia, Alopecia-Anosmia-Deafness-Hypogonadism, Alopecia-Onychodysplasia-Hypohidrosis, Alopecia-Onychodyaplasia-Hypohidrosis-Deafness, Alopecia Universalia-Onychodystrophy-Total Vitiligo, Amelocerebrohypohidrotic Syndrome, Ameloonychohypohidrotic Dysplasia Ankyloblepharon-Ectodermal Defects-Cleft Lip and Palate (AEC) Syndrome (also known as Hay Wells Syndrome), Anonychia With Bizarre Flexural Pigmentation, Arthrogryposis and Ectodermal Dysplasia, Baisch's Syndrome, Book's Dysplasia, Camarena Syndrome, Carey's Syndrome, Christ-Siemens-Touraine's (CST) Syndrome (also known as Hypohidrotic Ectodermal Dysplasia) , Coffin-Siris's Syndrome, Congenital Insensitivity to Pain With Anhidrosis, Congenital Lymphedema, Hypoparathyroidism, Nephrotathy, Prolapsing, Mitral Valve, and Brachytelephalangy, Cranioectodermal Syndrome, Curly Hair-Ankyloblepharon-Nail Dysplasia (CHANDS), Cystic Eyelids-Palmoplantar Keratosis-Hypodontia-Hypotrichosis, Dentooculocutaneous Syndrome, Dermotrichic Syndrome, Dermoodontodysplasia, Dyskeratosis Congenita, Ectodermal Defect With Skeletal Abnormalities, Ectodermal Dysplasia of the Head, Ectodermal Dysplasia With Palatal Paralysis, Ectodermal Dysplasia With Severe Mental Retardation, Ectodermal Dysplasia With Syndactyly, Ectodermal Dysplasia Syndrome With Tetramelic Deficiencies, Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate (EEC) Syndrome, Ellis-Van Creveld's Syndrome-Jacobsen-Clouston's Syndrome (also known as Clouston's Syndrome), Fischer's Syndrome, Focal Dermal Hypoplasia (FDH) Syndrome, Fried's Tooth and Nail Syndrome, Gingival Fibromatosis and Hyperrtrichosis, Gingival Fibromatosis-Sparse Hair-Malposition of Teeth, Gorlin-Chaudhry-Moss' Syndrome, Growth Retardation-Alopecia-Pseudoanodontia-Optic Atrophy(GAPO), Hallermann-Streiff's Syndrome, Hairy Elbows Dysplasia, Hayden's Syndrome, Haywells Syndrome, Hypertrichosis and Dental Defects, Hypodontia and Nail Dysgenesis, Hypohidrotic Ectodermal Dysplasia, Hypohidrotic Ectodermal Dysplasia - Autosomal Recessive, Hypohidrotic Ectodermal Dysplasia With Hypothyroidism, Hypohidrotic Ectodermal Dysplasia With Papillomas and Acanthosis Nigricans, Hypomelanosis of Ito Ichthyosiform Erythroderma-Deafness-Keratitis, Incontinentia Pigment I, Johanson-Blizzard's Syndrome, Jorgenson's Syndrome, Kirghizian Dermatoosteolysis, Lenz-Passarge's Dysplasia, Marshall's Syndrome I, Melanoleucoderma, Mesomelic Dwarfisn-Skeletal Abnormalities-Ectodermal Dysplasia, Mikaelian's Syndrome, Naefeli-Franceschetti-Jadassohn's Dysplasia, Oculodentodigital (ODD) Syndrome I, Oculodentodigital (ODD) Syndrome II, Oculoosteocutaneous Syndrome, Odontoonychodermal Dysplasia, Odontoonychodysplasia, Odontoonychodysplasia With Alopecia, Odontoonychohypohidrotic Dysplasia With Midline Scalp Defect, dontotrichomelic Syndrome, Onychotrichodysplasia With Neutropenia, Orofaciodigital (OFD) Syndrome I, Osteosclerosis and Ectodermal Dysplasia, Pachyonychia Congenita, Palmoplantar Hyperkeratosis and Alopecia, Papillon-Lefevre's Syndrome, Pili Torti and Enamel Hypoplasia, Pili Torti and Onychodysplasia, Rapp-Hodgkin's Syndrome, Regional Ectodermal Dysplasia With Total Bilateral Cleft, Robinson's Syndrome, Rosseli-Gulienetti's Syndrome, Rothmund-Thomson's Syndrome, Sabinas Brittle Hair and Mental Deficiency Syndrome, Salamon's Syndrome, Schinzel-Giedion's Syndrome, Skeletal Anomalies-Ectodermal Dysplasia-Growth and Mental Retardation, Syndrome of Accelerated Skeletal Maturation, Failure to Thrive and Peculiar Face, Trichodental Dysplasia, Trichodentoosseous (TDO) Syndrome I, Trichodentoosseous (TDO) Syndrome II, Trichodentoosseous (TDO) Syndrome III, Trichodysplasia-Onychogryposis-Hypohidrosis-Cataract, Trichofaciohypohidrotic Syndrome, Trichooculodermovertebral Syndrome, Trichoodontoonychial Dysplasia Trichoodontoonychodermal Syndrome, Trichoodontoonychodysplasia With Pili Torti, Trichoodontoonycho-Hypohidrotic Dysplasia With Cataract, Trichoonychodental (TOD) Dysplasia, Trichoonychodysplasia With Xeroderma, Trichorhinophalangeal (TRP) Syndrome I, Triphalangeal Thumbs-Onychodystrophy-Deafness, Walbaum-Deheane-Schlemmer's Syndrome, Xeroderma-Talipes-Enamel Defect, Zanier-Roubicek's Syndrome.
 * __Manifestations of Ectodermal Dysplasia:__-** As previously mentioned, ED presents in many different forms and is classisfied as several different syndromes. These include:


 * __ Causes- __** Ectodermal Dysplasia is caused by hereditary factors. There are many types of ED (as above) that depend on the type of gene mutation or inheritance patterns from occurring. The possible inheritance paterns include:
 * //Autosomal dominant//** and **//Autosomal recessive//** inheritance patterns are caused by mutations in the genes for the ectodysplasin receptor. In //Autosomal Dominant// inheritance the mutation occurs on the non sex linked chromosomes, and only one affected chromosome is needed for the trait to be passed on. In //Austosomal recessive// inheritance, two copies of the altered gene are needed for the trait to be passed on (both the mother and father would need to be carriers of the gene)

While there have been several inheritance patterns attributed to Ectodermal Dysplasia, not all of the genes for these have been mapped and there is still much research being conducted into the exact genes affected for each type of inheritance(Lingling, Williams &Spritz, 1998).
 * //X-linked dominant and X-linked recessive//** mutatations occur in the gene coding for the ligand ectodysplasin A. X linked inheritance is the most common type of inheritance associated with Ectodermal Dysplasia and is often more severe in males than in female cases. Not only is the X linked type of Ectodermal Dysplasia more severe in males, but it is also more commonly diagnosed in males, due to being on the X chromosome, if a male inherits this affected chromosome, they do not have another, non affected, chromosome to rely on as females do, instead the males have just the Y chromosome that cannot take place of an affected X chromosome (Sohrabi 2004). This means that in X linked recessive a female will need two copies of the altered gene to be affected whereas the male will only need one copy. (only one parent would have to have the affected chromosome)



In one particular type of ED, hypohydrotic ED, the mutation can occur on three separate genes EDA, EDAR, and EDARADD. These genes are responsible for making the proteins that work together during embryonic development and are crucial for the communication between cells of the ectodermal layer and the mesoderm layer that are the basis for the bodies organs tissues. (Genetics Home Reference, 2009). This particular inheritance is one of the most comon inheritance patterns for Ectodermal Dysplasia and shows how there is such a variation in the specific causes for each type of ED, not only increasing variation in the symptoms that occur but also increasing the difficulty in accuratley diagnosing the disease.
 * __Hypohydrotic ED__**

Ectopdermal Dysplasia can have several appearances, depending on what type of inheritance has occurred. Ectodermal Dysplasia affects the ectodermal structures and so presents as abnormalities in the teeth, skin, hair and sweat glands. Patients suffering from any form of ectodermal dysplasia will display at least two of the following clinical symptoms:
 * __Clinical appearance of ED:__**
 * Absent or malfunctioning sweat glands
 * Dental anomalies, including missing or underdeveloped teeth
 * Varying degrees of alopecia resulting from defective hair follicles
 * Malformed or missing fingers or toes
 * Malformed fingernails and toenails
 * Cleft lip/palate, deficient saliva, hearing and visual defects, and inadequate eye fluids and tears.
 * Neurologic and respiratory abnormalities may be present





Sweat gland function is usually altered with the ability to produce sweat potentially completely removed therefore causing problems with the body being able to maintain a normal and healthy body temperature and potentially leading to hyperthermia. Hair may be thin and very brittle, often having a light colour and being quite sparse, nails on the other hand are often thick and abnormally shaped and discoloured skin is often pigmented with red or brown discolouration occurring, the skin can often be thick and dry over the palms and soles of feet.

People who suffer from Ectodermal Dysplasia may, in severe cases, also have some problems with vision, having dry and red eyes and often also having problem with cataracts, as well as possibly having some hearing difficulties. The teeth are the most obviously affected ectodermal structure, with the tooth bud being affected during development and therefore causing agenisis (missing teeth) or anomalies. These can include peg laterals or mishapen teeth that can cause major problems for function of the teeth with mastication, speech, and aesthetic problems. The enamel on the teeth may also be defective which can cause an increased risk for caries and decay as well as erosion (National Foundation for Ectodermal Dysplasia 2009). Along with the teeth being affected, other dentally relevant problems associated with Ectodermal Dysplasia is the reduction in mucous and salivary secretions. This reduction in saliva may mean the patient suffers from a dry mouth and will have a poor buffering capacity, potentially leading to a greater caries risk, as well as being more susceptible to respiratory infections as the mucous production is reduced and therefore the protective mechanism for the respiratory system is also compromised (Dental Implant Centre 2009).

There are no absolute tests to determine each type of Ectodermal Dysplasia, however there are several DNA tests that can be carried out to determine some of the more common types of ED and there is a prenatal diagnosis available for families that have already been diagnosed both X-linked hypohydrotic ED through the use of a DNA probe (Sohrabi, 2004).
 * __Diagnosis:__** A correct diagnosis is necessary for prognosis and to anticipate what kinds of problems an individual with Ectodermal Dysplasia may have, or to reduce concern about what problems may or, may not arise however this is oftern difficult. Symptoms may be obvious from birth, however often syptoms are not noted until children are slighlty older and teeth fail to develop normally. It is important when diagnosing ED that all the potentially affected structures are examined carefully. Tests of the mucous membranes can be used to determine if there is abnormal mucous production or mucous glands.

As previously outlined, the wide variety of physical symptoms related to ectodermal dysplasia arise from "the absence, or deficient function, of atleast two derivatives of the ectoderm" (Bissonnette 2006). The table below summarises the most common and relevant physical symptoms of ectodermal dysplasia and the physiological cause/effect: Abnormality in the molecular structure of Keratin
 * __Physiological consequences of ED:__**
 * Symptom of Ectodermal Dysplasia || Physiological Cause || Physiological/Physical Effect ||
 * **Clouston Syndrome** ||

Physical effects suggest a biochemical defect in the keratin of integumentary system ||  ||
 * Palmoplantor hyperkeratosis ||^  || Hyperkeratotic Skin ||
 * Nail dystrophy ||^  || Nail are thickened, striated, discoloured and slow growing. ||
 * Alopecia ||^  || Hair shows altered organisation of fibrils with loss of cuticular cortex ||

There are not only problems associated with the teeth directly, but also with the surrounding areas such as the ears, nose and throat, with the mucous secretions in the nose being extremely thick and often having nasal infections that may have the potential to spread to surrounding areas. Salivary glands are also affected by Ectodermal Dysplasia often causing them to have a reduced function, or not be present at all. This underproduction of saliva causes problems for patients oral environment, making functions such as chewing, swallowing and tasting more difficult, and also affecting speech as the mouth is dry and more difficult to manouver (National foundation for ectodermal Dysplasia, 2009). Due to the decreased salivary flow, there is also a large increase to caries risk and other oral infections to occur as the normal buffering capacity of the saliva is removed and the ability for oral clearance to occur is removed meaning that harmful bacteria remain in the mouth for longer. ​
 * __Implications__**: Dental defects represent the primary clinical feature for the majority of EDs. These defects may include: polydontia, anodontia, dysplastic teeth, deficient enamel development (amelogenesis imperfecta), retained primary teeth, dentine deficency (dentinogenesis imperfecta) and underdevelopment of the alveolar ridge. For some EDs, the spacing of the teeth is disrupted due to a reduction in the number of erupted teeth and the periodontium is affected. A distrubance in the enamel matrix may also occur, making teeth more susceptible to caries and also altering the shape of the teeth, leading to a pegged shape appearance and additional cusps. (Freiman et al 2009)
 * __Treatment:__** Ectodermal Dysplaisa has no specific treatment avaliable, however, with the work of many specialised practitioners, the symptoms can be aleviated sligtly to improve the quality of life. Dental treatment is often necessary in patients with some forms of ED. Historically, prosthetic treatment for ED patients involved removable partial dentures, removal partial or complete overlay dentures and fixed partial dentures(Sweeney et al 2005). Some children may require serial sets of dentures from as early as 2 years of age (Yenisey et al 2004). The use of dental implants is also a well-established treatment modality in patients who have ceased growth and have also proved effective in certain situations in growing indivduals including those with ED, however lack of development of alveolar ridge anatomy may be a factor associatied with implant failure in ED patients (Sweeney et al 2005). It is also important to seek dental advice early as maintenance of the alveolar ridge is important for later dental intervention. Prosthetic teeth are implanted in adults for mastication and speech. Importantly, aesthetic dental intervention in patients with ED and malformed teeth amd malocclusion helps with the development of a positive self-image and overall oral health (Ohno et al 2000). Oral rehabilitation in a child patient has a major psychological impact on their self esteem and facilitating social acceptance and early studies in children demonstrated a marked change in a personality, speech and vocabulary 8 weeks after insertion of complete dentures (Herer PD 1975).

D​ental treatment costs for EDs are also expensive. Because early intervention and sustained treatment are required if a patient with ED is to receive optimal dental treatment, the costs incurred by affected families can become a considerable financial burden (Murdoch et al 2005). Dental treatment for EDs requires a dental team approach which may include input from a general dentist, a prosthodontist, an orthodontist and an oral maxillofacial surgeon. A recent study (Sean Murdock, Jessica Lee, Albert Guckes et al.) showed depending on the age of the patient and range of treatment, the costs associated with dental treatment for EDs varied widely. They ranged between $2,038 and $3,298 for those who received prosthodontic treatment only and between $12,632 and $41,146 for those who received a combination of prosthodontic, orthodontic and implant treatment. This information could help general dentist understand the cost implications for their patients. In turn, it could help them better inform families and help families plan for the future treatment of their children by giving them an idea of the cost involved in the required dental treatment after the diagnosis of ED has been made for their child.

Each individual patient will display their own set of symptoms according to the type of ectodermal dysplasia they are affected by. If the patient has reduced sweat gland function or has no sweat glands present, then it is the operator’s duty to ensure the surrounding clinic temperature is set at a comfortable level. In extreme cases where this is ignored, the patient may become hyperthermic and this abnormally elevated body temperature can result in further disability or death. Another common manifestation of ectodermal dysplasia is the absence or malfunction of respiratory mucous glands. As patients with ectodermal dysplasia can also have mildly suppressed immune systems, this leaves them extremely susceptible to respiratory tract infections (Bissonnette 2006). This can be fatal and alterations may need to be made in the clinic to reduce the amount of airborne bacteria in the surrounding environment. Use of high quality air-filters in the air-conditioning systems and providing the patient with a mask while they are in the waiting room are a couple of simple ideas that would be beneficial in this situation. If general anaesthesia is required for the patient during a procedure then humidified-air should be used as the respiratory tract is unable to produce sufficient moisture. It should also be noted that there have been reports of abnormal bleeding tendencies in patients with certain forms of ectodermal dysplasia. Thus dental operators must always assume the worst and ascertain a complete blood cell count with white cell differentiation and a coagulation screen before carrying out intrusive procedures such as scaling (Bissonnette 2006). This is because if patients do not have competent blood clotting function they may suffer from possible life treatening affects. Alternative suggested methods to improve patient sypmtoms include encouraging frequent consumption of cool liquids to maintain adequate hydration and thermoregulation, advise patients to wear cool clothing (Shah 2009), wigs in cases of severe alopecia, artifical tears can be used to replace normal tearing and prevent dry eyes, saline nostril sprays can be used to remove debris and prevent infection, people with ED can choose to live in a cooler climate and take cooling baths to help maintain a normal body temperature as the water evaporating from the skin will have the same cooling function as sweat (Leher, 2008). Investments in the molecular biology of genes and their regulation and function now also provide more than 30 candidates for specific biomarkers to improve diagnosis, prognosis, treatments, therapeutics, and biomaterials for EDs. Innovations in high throughput genotyping, gene mapping, single nucleotide polymorphisms (SNPs), interference RNA treatments, bioimaging, tissue engineering and related biomimetic approaches to design and fabricate biomaterials, offer enormous promise for the future of Ectodermal Dysplasias.
 * __Management within the dental clinic:__** Special treatment requirements and factors need to be taken into consideration when dealing with a patient suffering from ectodermal dysplasia in a clinical situation.


 * __References:__**

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