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Hypohidrotic ectodermal dysplasia

This is part of Rare diseases.

Diagnosis: Hypohidrotic ectodermal dysplasia

Synonyms: Anhidrotic ectodermal dysplasia, Ectodermal dysplasia, Christ-Siemens-Touraine syndrome

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Publication date: 25/10/2011
Version: 4.1

ICD 10 code

Q82.4

The disease

Hypohidrotic ectodermal dysplasia is one of a group of diseases with the collective name ectodermal dysplasias. Other names for the disorder include anhidrotic ectodermal dysplasia (EDA) and Christ-Siemens-Touraine syndrome.

Hypohidrosis is associated with an impaired ability to sweat. Ectodermal dysplasia refers to defects in the ectoderm, the structures which in the early stages of foetal development become the skin, hair, teeth, nails and secretory glands (tear glands, salivary glands, and mucous glands in the throat, larynx, respiratory system and intestinal tract).

The condition was described in 1848 by British physician J. Thurnam. There are approximately 190 different types of ectodermal dysplasia, with symptoms affecting the teeth, sweat glands, skin and hair. Hypohidrotic ectodermal dysplasia is the most common form.

There is a form of hypohidrotic ectodermal dysplasia which occurs only in boys and which gives recurring, difficult-to-treat, infections. In the Swedish Board of Health and Welfare’s Rare Disease Database there is separate information material on hypohidrotic ectodermal dysplasia with immune deficiency.

Occurrence

The syndrome takes its most severe form in boys. International medical literature estimates an incidence of between 1 and 7 boys with the disease in every 100,000 births. However, as knowledge of the syndrome increases, the condition is diagnosed more frequently. Often several members of a single family are affected. It is estimated that there are at least 100 cases of hypohidrotic ectodermal dysplasia in Sweden.

Cause

Hypohidrotic ectodermal dysplasia is usually caused by a mutation in the EDA gene on the X chromosome (Xq12-q13.1). EDA controls the development of (codes for) the protein ectodysplasin A. This protein in its turn controls the development of ectodermal tissue. There are many mutations of the gene, but only one specific mutation causes the disease in an individual or family group. Mutations in the EDAR gene (2q11-q13) and the EDARADD gene (1q42.2-q43) can also cause hypohidrotic ectodermal dysplasia, but this is considerably more rare.

Heredity

Most cases of the disease are caused by a mutated gene located on the X chromosome, which is one of the chromosomes which determines sex. Men have one X chromosome and one Y chromosome, while women have two X chromosomes. Inherited X-linked recessive disorders usually occur only in men, being passed down via a healthy female carrier who has one normal and one mutated gene. Female carriers can develop a milder form of the disease. Sons of female carriers of a mutated gene run a 50 per cent risk of inheriting the disease and daughters run the same risk of being healthy carriers of a mutated gene. A man with an inherited X-linked recessive disease cannot pass it on to his sons, but all his daughters will be carriers of the mutated gene.

Figure: X-linked recessive inheritance  via a healthy female carrier

Mutations in EDAR and EDARADD can follow both autosomal recessive and autosomal dominant patterns of inheritance. The symptoms are the same as in the X chromosome-linked forms of the disease, the difference being that in these forms, girls’ symptoms are just as severe symptoms as boys’.

An autosomal recessive form of inheritance means that both parents are healthy carriers of a mutated gene. When two healthy carriers have a child, there is a 25 per cent risk that the child will inherit the mutated genes (one from each parent) in which case he or she will have the disease. In 50 per cent of cases the child inherits only one mutated gene (from one parent only) and like both parents, will be a healthy carrier of the mutated gene. In 25 per cent of cases the child will not have the disease and will not be a carrier of the mutated gene.

Figure: Autosomal recessive inheritance 

A person with an inherited autosomal recessive disease has two mutated genes. If this person has a child with a person who is not a carrier of the mutated gene, all the children will inherit the mutated gene but they will not have the disorder. If a person with an inherited autosomal recessive disease has children with a healthy carrier of the mutated gene (who has one mutated gene) there is a 50 per cent risk of the child having the disorder, and a 50 per cent risk of the child being a healthy carrier of the mutated gene.

Figure: Autosomal dominant inheritance

An autosomal dominant pattern of inheritance means that one of the parents has the disease, and so has one normal gene and one mutated gene. Sons and daughters of this parent have a 50 per cent risk of inheriting the disease. Children who do not inherit the mutated gene do not have the disease and do not pass it down.

Symptoms

People with hypohidrotic ectodermal dysplasia lack sweat glands, or have glands whose function is impaired. This means that the body’s natural heat regulatory system, needed to lower the body temperature in warm environments and in cases of fever, is deficient. For this reason, the body temperatures of children with hypohidrotic ectodermal dysplasia may easily become elevated and even mild infections may induce a fever. To avoid complications, fever must be treated promptly and the child’s temperature brought down. The risk of becoming overheated during periods of fever, or in warm spells, is present from birth.

Both adults and children with the syndrome may have problems in warm weather, in hot indoor environments and during physical exercise. For children and young people of school age it may be difficult to participate fully in exercise classes or in certain team sports. Signs of overheating include headache, irritability, sleepiness, fainting and, in severe cases, seizures. Overheating (heat stroke) is a serious condition that can be life-threatening, for example during heat waves or severe infections.

Children with ectodermal dysplasia are often of normal height, but weigh less than average. This may be caused by the child’s missing teeth, which makes chewing difficult, and the fact that some small children with the syndrome have difficulty swallowing, and an increased tendency to vomit.

The majority of boys and adult men with the form of the disease linked to the X chromosome have lower than average BMI (body mass index) and less subcutaneous fat than normal. They may be particularly sensitive to cold.

The syndrome is also associated with a partial or total absence of primary teeth and permanent teeth. A few people with hypohidrotic ectodermal dysplasia have no teeth, in one or both jaws. There are almost always more tooth buds in the upper than the lower jaw. The jaw bones in the areas without teeth will not grow normally. The first primary teeth usually erupt six months to a year later than average. Teeth are often small and the front teeth may be pointed and conical. If several teeth are missing, the palate is often flat and the bite (the vertical space between the teeth) low.

The skin is thin, fair, smooth and dry, owing to the absence of sebaceous (oil-producing) glands and the reduced number of sweat glands. Atopic eczema is common. The skin around the eyes often looks dark owing to increased keratinisation. Sometimes nails may be thin and brittle.

Hair on the head is sparse, and often thin, fair and coarse in structure or may be entirely absent. Generally it grows very slowly and is often dry due to the lack of sebaceous glands in the scalp. Dandruff is also common. There may be increased hair growth during puberty. Many men with the syndrome may have not hair on their arms and legs but nevertheless have normal beard growth.

As a result of constricted tear ducts or a deficiency in the tear glands, some people with the disease have dry eyes. This can cause eye inflammation, over-sensitivity to light or damage to the corneas.

Ear wax is often thick and sticky. Hearing can be affected if wax accumulates in the ear or the auditory tube becomes blocked while the ear is inflamed. There is also an increased risk of developing infections of the middle ear.

The ability to smell and taste may be impaired. The salivary glands are sometimes absent or may not function properly. Low salivary secretion results in a dry mouth and increases the risk of caries. The absence of mucous glands in the nose and throat causes dryness, which increases the risk of infections in the nose, throat and respiratory system. Foul-smelling dry scabs may develop in the nose. A dry throat resulting from the reduced production of saliva and mucus may cause hoarseness and soreness when speaking, and also cause swallowing problems. Asthma and allergies may also occur. As the mouth may be dry and some teeth absent, speech may be unclear.

Children under the age of three with the syndrome often vomit while eating. After this age, vomiting often becomes less frequent. Some people may suffer from constipation caused by too few mucus-producing glands in the intestines.

Boys with X chromosome-linked hypohidrotic ectodermal dysplasia have characteristic facial features including a wide forehead, pronounced eyebrow arches and deeply-set eyes surrounded by fine wrinkles and darker skin. The bridge of the nose is sunken. The lips are full and protuberant.

Women with the syndrome may have the same symptoms as men, including sparse hair growth and abnormal dentition, but in a far less severe form. Many women are not diagnosed as they do not seek medical or dental help for their condition. The nipples and mammary glands may be underdeveloped or absent, making it difficult or impossible to breast-feed. Some women may also experience dryness in the vaginal area.

Diagnosis

Early diagnosis is important to help prevent complications owing to overheating. A paediatrician, dermatologist and paediatric dentist should be involved in diagnosing the syndrome. In most cases, however, the child is not diagnosed until the age of 12 to 18 months, when the teeth are still absent or the first tooth has an abnormal, conical shape.

The diagnosis is based on a characteristic appearance, and symptoms. At birth the skin may be covered with a glue-like membrane (collodion baby). The membrane splits and falls off at a time which can vary between a few days, or several weeks, after birth. Children with the syndrome often look the same as other children but they have fair, thin, very dry skin and little or no hair on the head or body at birth. The number of tooth buds present in the jaws can be determined by means of an X-ray when the child is between the ages of six and eight years old.

A detailed family history identifying other family members with hypohidrotic ectodermal dysplasia, facilitates an early diagnosis. The severity of the condition varies from family to family, as well as within families. After one family member has been diagnosed, affected relatives with less obvious symptoms are sometimes identified.

DNA-based, pre-natal and embryo diagnoses are all possible. Genetic counselling should be offered when the diagnosis is given.

Treatment/interventions

Children with symptoms of hypohidrotic ectodermal dysplasia should be referred to medical professionals including a paediatrician, dermatologist, ophthalmologist and specialist in paediatric dentistry. A team of dental professionals including specialists in paediatric dentistry, orthodontics, prosthetic dentistry and oral surgery should be involved in planning the child’s dental care.

It is important that overheating is avoided. (Read more under “Practical Advice.”) As the condition is associated with poor heat regulation, fever should always be treated. Fever-reducing medication should be given every four to six hours for 24 hours. The morning temperature the next day determines whether or not the treatment should be continued. It is important to avoid physical exertion if the child has a high temperature.

If a person with hypohidrotic ectodermal dysplasia is about to undergo general anaesthesia it is important that the anaesthesiologist is informed about the patient’s poor temperature regulation, and about the dry, sensitive mucous membranes in the throat and nose.

As people with the syndrome will require dental treatment throughout their lives, it is important that a specialist in paediatric dentistry introduces the child to dental treatment at an early age. The family should be informed about short and long-term treatment options for replacing missing teeth. Removable prostheses can sometimes be worn from the age of three or four, and at a later age prostheses fixed to existing teeth or dental implants, can be made.

A dental X-ray should be taken before the child reaches school age and salivary flow rates should be measured as soon as the child is able to cooperate. Reduced levels of saliva are associated with an increased risk of caries. Recommended preventive treatments include fluoride rinsing and fluoride tablets. Regular examinations and the application of fluoride varnish should be carried out by a dental hygienist or prophylactic nurse.

Pointed teeth can be remodelled to improve speech and facilitate eating, as well as for cosmetic reasons. This treatment applies to both primary and permanent teeth. Orthodontic treatment is often necessary to re-position teeth before dental replacements are made. All interventions should be planned by a team of specialists in paediatric dentistry, orthodontics and prosthodontics (tooth replacement). Frequently, varying types of removable and fixed prostheses are worn at different ages. Because these children often have difficulties chewing hard, tough foods, they may require special meals at pre-school or school. For this, they may need a supporting letter from a doctor or dentist.

The first permanent treatment is not carried out until the jaw is fully developed, from about the age of twenty. Adults with hypohidrotic ectodermal dysplasia may apply to their local Swedish county council to pay the same fees for dental as for medical care. ( See,“Tandvård som ett led i sjukdomsbehandling.” In Swedish only.)

Individuals with hypohidrotic ectodermal dysplasia require treatment by a dermatologist. The skin is treated with a moisturiser and bath oil. Atopic eczema is usually treated with a moisturiser and/or cortisone ointment.

Narrow tear ducts may require treatment and sometimes surgical intervention. Dry eyes are relieved using eye drops three to four times a day.

Blocked ears can be syringed after treatment with eardrops. In cases of recurrent middle ear infections and persistent auditory tube inflammations (otosalpingitis), an ENT specialist should be consulted to examine and treat the patient.

Blowing the nose may be difficult when the mucous membranes are dry, and hard scabs with an unpleasant odour can develop. These scabs can also interfere with the senses of taste and smell. It may be necessary to rinse the nose with a saline solution morning and evening, or to see an ENT physician for rinsing. There are also oil-based nasal sprays that help prevent fissures in the mucous membranes.

Constipation may be alleviated by increasing fluid intake and dietary fibre. In severe cases, medication may be prescribed.

Information to pre-school and school staff is essential as children with the syndrome require supervision during play and sports activities. It is particularly important that physical education teachers are informed about the condition. This will increase their understanding of the problem and also make them aware that the child may not be able to participate in certain activities. As the disorder is very rare, it may be helpful if the doctor issues a medical certificate attesting that the child may not always be able to participate in physical education classes.

Social and psychological support may be necessary.

Practical advice

From infancy, children with the syndrome should be allowed to sleep naked and without covers. Air conditioning in the home and school may be desirable, particularly in summer when the child is playing indoors or when he/she wishes to cool down. Air conditioning is important when riding in a car on sunny days. A spray bottle of water, a plastic bag of ice cubes, or a wet towel in a cooler bag are also helpful aids in hot weather. During physical exercise, especially in the summer, a wet T-shirt can help cool the body. A hat or cap and sunglasses are recommended when the weather is sunny. Special cooling vests and hats can be purchased, and may be well worth trying.

In Sweden, it is possible to receive a housing adaptation allowance to install air-conditioning in the home, but this requires a medical certificate. Allowances are also available for the purchase of wigs.

National and regional resources in Sweden

Specialised knowledge of, and expertise in, hypohidrotic ectodermal dysplasia may be found at The National Oral Disability Centre, The Institute for Postgraduate Dental Education, P O Box 1030, SE-551 11 Jönköping, Sweden. Tel: +46 36 32 46 66, fax: +46 36 32 46 67, email: kompetenscenter@lj.se.

Another national centre of excellence is the Centre for Inherited Skin Diseases, Dermatology Clinic, University Hospital Uppsala, which specialises in certain types of inherited skin diseases. See under “Resource Personnel.”

Resource personnel

Senior consultants Birgitta Bergendal, LDS, PhD, and Johanna Norderyd, LDS, National Oral Disability Centre, The Institute for Postgraduate Dental Education, Box 1030, SE-551 11 Jönköping, Sweden. Tel +46 36 32 46 68, and +46 36 32 46 65. Fax: +46 36 32 46 67, email: birgitta.bergendal@lj.se or johanna.norderyd@lj.se.

Professor Niklas Dahl and Dr Maritta Hellström Pigg, Department of Clinical Genetics, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Tel: +46 18 611 49 50.
Professor Anders Vahlquist, Dermatology Clinic, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Tel: +46 18 611 00 00, fax: +46 18 611 26 80, email: anders.vahlquist@medsci.uu.se.

Courses, exchanges of experience, recreation

Ågrenska is a national competence centre for rare diseases and its families’ programme arranges stays for children and young people with rare diseases and their families. Ågrenska is open to families from the whole of Sweden and focuses particularly on the needs of children and young people with rare diseases. Every year a number of adults with rare diseases also visits Ågrenska. Information is available from Ågrenska, Box 2058, SE-436 02 Hovås. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se, www.agrenska.se.

Organizations for the disabled/patient associations

The Swedish ED (ectodermal dysplasia) Society, Chairperson Jenny Eriksson, email: ordforande@svenskaed.se, www.svenskaed.se

The National Association of Rare Diseases, Box 1386, SE-172 27 Sundbyberg, Sweden. Tel: +46 8 764 49 99, email: info@sallsyntadiagnoser.se, www.sallsyntadiagnoser.se.
The Association is a national organisation working for people living with rare diseases and associated disabilites.

In the US there is a support group for ED: National Foundation for Ectodermal Dysplasias, 410 E. Main Street, PO Box 114, Mascoutah, Illinois USA, 62258-0114. Email: info@nfed.org, www.nfed.org.

Courses, exchanges of experience for personnel

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Research and development (R&D)

Genetic research is developing rapidly and during the last twenty years advances have been made in understanding the genetic aspect of tooth development. The list of genes known to regulate the position, shape and number of teeth is steadily increasing. During foetal development these genes govern intercellular communication via networks of tiny signal molecules. Advances in knowledge about tooth development in combination with recent breakthroughs in stem cell research indicate that in the future it may be possible to create new teeth artificially.

Information material

An information leaflet on hypohidrotic ectodermal dysplasia that summarises the information in this database text is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2011-6-4.) Address: SE-120 88 Stockholm, Sweden. Tel: +46 75 247 38 80, fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se. Postage will be charged for bulk orders.

“About Anton,” a film on hypohidrotic ectodermal dysplasia, produced by the National Oral Disability Centre in Jönköping, Sweden. The film is ten minutes long and can be borrowed from the National Oral Disability Centre. (See address under, “Resources.”)

Guidelines for the treatment of hypohidrotic ectodermal dysplasia were drafted at a consensus conference in 1998, and were later adopted by the Swedish ED Association. The guidelines are available on http://plus.lj.se/info_files/infosida25819/vardprogramed.pdf.  They can also be ordered from the National Oral Disability Centre in Jönköping. (See address under “Resources.”)

Newsletter from Ågrenska, nr 327 (2008). Can be ordered from Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se. Newsletter is also available at www.agrenska.se.

Ågrenska also publishes information on living with the disorder as an adult: www.agrenska.se/Nksd/Vuxen-att-leva-med/Att-vara-vuxen-och-leva-med-Hudsjukdom/.

Literature

Bergendal B. Prosthetic habilitation of a young patient with hypohidrotic ectodermal dysplasia and oligodontia. A case report of 20 years treatment. Int J Prosthodont 2001; 14: 471-479.

Bergendal B, Koch G, Bergendal T, Hallonsten A-L, Kvint S. A multidisciplinary approach to oral rehabilitation with osseointegrated implants in children and adolescents with multiple aplasia. Eur J Orthod 1996; 18: 119-129.

Bergendal T, Eckerdal O, Hallonsten A-L, Koch G, Kurol J, Kvint S. Osseointegrated implants in the oral habilitation of a boy with ectodermal dysplasia: a case report. Int Dent J 1991; 41: 149-156.

Bergendal B. Oligodontia and ectodermal dysplasia-on signs, symptoms, genetics, and outcomes of dental treatment. Swed Dent J Suppl 2010; 205: 13-78, 7-8.

Ferguson BM, Thomas NST, Munoz F, Morgan D, Clarke A, Zonana J. Scarcity of mutations detected in families with X linked hypohidrotic ectodermal dysplasia: diagnostic implications. J Med Genet 1998; 35: 112-115.

Kere J, Srivastava A, Montonen O, Zonana J, Thomas N, Ferguson B et al. X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein. Nat Genet 1996; 13: 409-416.

Lexner M.O, Bardow A, Bjorn-Jorgensen J, Hertz JM, Almer L, Kreiborg S. Anthropometric and cephalometric measurements in X-linked hypohidrotic ectodermal dysplasia. Orthod Craniofac Res 2007; 10: 203-215.

Mehta U, Brunworth J, FeteTJ, Sindwani R. Head and neck manifestations and quality of life of patients with ectodermal dysplasia. Otolaryngol Head Neck Surg 2007; 136: 843-847.

Mikkola ML. Molecular aspects of hypohidrotic ectodermal dysplasia. Am J Med Genet A 2009; 149A: 2031-2036.

Motil KJ, Fete TJ, Fraley JK, Schultz RJ, Foy TM, Ochs U et al. Growth characteristics of children with ectordermal dysplasia syndromes. Pediatrics 2005; 116: 229-234.

Nordgarden H, Jensen JL, Storhaug K. Oligodontia is associated with extra-oral ectodermal symtoms and low whole salivary flow rates. Oral Dis 2001; 7: 226-232.

Nordgarden H, Storhaug K, Lyngstadaas SP, Jensen JL. Salivary gland function in persons with extodermal dysplasias. Eur J Oral Sci 2003; 111: 371-376.

Thesleff I. The genetic basis of tooth development and dental defects. Am J Med Genet A 2006; 140: 2530-2535.

Thurnam J. Two cases in which the skin, hair and teeth were very imperfectly developed. Medico-Chir Trans 1848; 31: 71.

Zonana J, Jones M, Clarke A, Gault J, Muller B, Thomas NS. Detection of de novo mutations and analysis of their origin in families with X-linked hypohidrotic ectodermal dysplasia. J Med Genet 1994; 31: 287-292.

Database references

OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim 
Search: ectodermal dysplasia 1, anhidrotic

GeneReviews (University of Washington)
www.genetests.org (find GeneReviews, then Titles)
Search: hypohidrotic ectodermal dysplasia

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft material is Senior Dental Surgeon, Birgitta Bergendal, National Oral Disability Centre, Jönköping, Sweden. Professor Niklas Dahl, Uppsala University Hospital, Sweden has also been involved in producing the material.

The material has been revised by Senior Dental Surgeon, Birgitta Bergendal, Institute of Odontology, Jönköping.

The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Publication date: 25/10/2011
Version: 4.1
Publication date of the Swedish version: 10/08/2011

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden. Tel: + 46 31 786 55 90, email: ovanligadiagnoser@gu.se.

 

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This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.