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Ectodermal Dysplasia

Ectodermal Dysplasias

Ectodermal dysplasia is an inherited condition, characterized by the defective development of the skin and its appendages, namely hair, sebaceous glands, nails and other structures.


Presentation

The typical presentation of a person born with ectodermal dysplasia may involve many of the following characteristics:

  • Extremely fine and fragile hair, often light in color, that is dispersed across the head. Alopecia is a common feature and may be accompanied by inflammation. In the same manner, facial hair (eg. eyebrows) are also scanty or absent.
  • Anomalies of the teeth are also typical: teeth have irregular shapes and are often pointed towards the ends. Enamel is dysplastic and many patients fail to grow the normal amount of teeth.
  • Onychodystrophia is also a frequent manifestation. Nails may be irregular in shape, too thick or even absent. The tissues adjacent to the nails are often susceptible to infection.
  • Abnormally developed or absent major sweat glands. This feature can threaten the lives of newborns, since failure to sweat leads to an increased body temperature, fever and neurological complications. Depending on whether the sweat glands are reduced in numbers, underdeveloped or completely absent, an individual may be able to produce reduced amounts of sweat (hypohidrosis) or no sweat (anhidrosis).
  • Skin hamartomas or skin cancer of various subtypes
  • Acanthosis nigricans
  • Systemic involvement

Hypohidrotic ectodermal dysplasia is the most common type of ectodermal dysplasia. Apart from the aforementioned typical characteristics concerning the hair, teeth and nails, these individuals do not produce the adequate amount of sweat to achieve the necessary detoxification and temperature regulation. other than that, they exhibit a characteristic appearance with hollowed cheeks, thick lips, and creased skin around the eyes. On the other hand, hidrotic ectodermal dysplasia is one of the syndromes inherited in an autosomal dominant manner, evincing a distinct predilection for people of French-Canadian descent. [10] [11] [12]. Patients exhibit no irregularities in the production of sweat, but may have conjoined fingers or more than 5 fingers in each hand.

Cerebellar Ataxia
  • Gonnelli, Ectodermal dysplasia syndrome with eyebrow alopecia, ptosis, strabismus, nystagmus, joint laxity, cerebellar ataxia, and osteopenia, American Journal of Medical Genetics, 113, 1, (111-113), (2002). R. Zannolli, E. Conversano, L.[doi.org]
Intracranial Hemorrhage
  • RESULTS: After 2 years, intracranial hemorrhage was detected at his regular radiological check-up and he again underwent surgery. The histological diagnosis was CVA.[ncbi.nlm.nih.gov]

Workup

In families with a medical history of ectodermal dysplasia, genetic testing may help to achieve a diagnosis of the condition before birth. Should the specific mutation be known, direct analysis can help to illustrate whether the child is affected or not. Chorionic villus sampling can also be of use, because a linkage analysis can be applied to determine the existence of an ectodermal dysplasia.

After birth, a skin biopsy can be performed in children whose appearance or periodic fever raises suspicion for the condition. The absence of eccrine glands or the presence of hypoplastic glands usually points to the direction of ectodermal dysplasia. Pore sweat counts can also be performed. Plain radiographs of the limbs can illustrate skeletal deformities and an orthopantography can examine the teeth, in order to detect possible anomalies. If a patient is affected by an ectodermal dysplasia syndrome with immunodeficiency, they have to be monitored closely for a potentially reduced concentration of immunoglobulins, a defective lymphocyte proliferation and T-cell immunity.

Treatment

Patients with ectodermal dysplasia receive supportive treatment, since the conditions cannot be cured.

More specifically, patients can benefit from an assessment by an orthodontist or dentist specializing in prosthetics, since the latter can be used to restore a normal appearance of their teeth. Children should follow a responsible dental hygiene plan [13] [14]. Patients who display inability to produce the adequate amount of sweat due to hypoplasia of the eccrine glands should be encouraged to use air conditioning electronics, wear clothes that allow for the body to be cooled and consume liquids in order to compensate for the failure of the natural homeostatic mechanism. Alopecia can be treated with the local administration of minoxidil products and the skin should always by maintained moist, with the use of creams and emollients [15]. Antibiotics, either per os or applied locally can also help to prevent infection in people with dermatitis; frequent infections may also be experienced by patients who have a compromised immune system, in which case appropriate follow-up should be adhered to.

Surgical intervention may be needed in cases of a cleft palate or lip, syndactyly or polydactyly. In general, ectodermal dysplasia is a group of conditions that requires the cooperation of an extensive and multi-disciplinary team of doctors in order for the appropriate management of the condition to be possible.

Prognosis

Individuals born with ectodermal dysplasia have unaffected intelligence and are usually subject to no significant morbidity or mortality. More severe cases of hypohidrosis need to be diagnosed at a very young age and managed appropriately, so as for the child to grow normally. The type of ectodermal dysplasia that is followed by the poorest prognosis is the one accompanied by immunodeficiency: mortality/morbidity are attributed to the defective immune system.

Etiology

Until now, approximately 200 conditions have been classified, which all fall under the category of ectodermal dysplasia syndromes, since they involve abnormalities of the products of the embryonic ectoderm. Nearly 8 out of 10 patients suffer from the Christ-Siemens-Touraine syndrome, a condition otherwise referred to as X-linked recessive hypohidrotic ectodermal dysplasia. 1 in 1,000,000 people are believed to be affected by it and the precise genetic loci of the abnormal gene are Xq12-q13.1 [1].

Ectodermal dysplasia conditions were first categorized in 1982 [2], with the next attempts being no sooner than 1994 [3] [4]. The initial categorization systems separated and identified them depending on the pathologically developed structures, such as hair, teeth, nail and eccrine glands. More recent approaches utilized the newly-discovered genetic substrate of these conditions and the most popular categorization is, until now, the following:

  • Related to the existence of cell-to-cell communication, adhesion, development, other [5]
  • Related to the existence of anomalies of developmental regulation or mesenchymal interaction and irregularities of cytoskeleton stability and cellular maintenance [6]

Some of the most frequently observed ectodermal dysplasia syndromes are the following:

Epidemiology

Ectodermal dysplasia is a condition which is congenital. Depending on the particular structures that are affected, it may remain undiagnosed until a child reaches the age of infancy, when these characteristics can be recognized as defective. In general, 1 out of 100,000 individuals in the United States is believed to be affected by the most common type of ectodermal dysplasia (hypohydrotic), whereas at an international level, the frequency seems augmented, with 70 out of 100,000 individuals suffering from it.

Ectodermal dysplasia syndromes are inherited in various ways. The most common hypohydrotic type is passed down from one generation to the other via the X-linked recessive pathway, which means that female patients are mere carriers, and affected males experience the full effect of the condition. Other X-linked ectodermal dysplasias include:

The remaining syndromes are not inherited via the X-linked pathway and therefore do not affect male and female patients in different ratios.

The severity of the condition depends on whether the mucous and major sweat glands are dysplastic. Abnormal development of these glands may lead to frequent, periodic episodes of fever, which can induce epileptic phenomena and further neurological damage. Children with ectodermal dysplasia typically exhibit hindered growth [8] and often display dermatitis, which leads to loss of hair due to frequent infections.

Sex distribution
Age distribution

Pathophysiology

The ectoderm is one of the three layers of cells that develop during embryogenesis and from which all other structures of a fully developed embryo are formed. The ectoderm is the exterior layer, followed by the mesoderm and endoderm. The structures that are a result of the ectodermal differentiation are the nervous system, the teeth, the skin and, subsequently, the skin's appendages as well. Ectodermal dysplasia occurs due to a failure of the embryonic ectoderm to differentiate normally, thus producing defective and abnormal structures.

Nearly 200 conditions induced by the faulty development of the ectoderm have been categorized and are all caused by genetic mutations. Other significant factors that have been found to participate in the pathogenesis of ectodermal dysplasia are the tumor necrosis factor (TNF)-like/TNV receptor signaling pathway, ectodysplasin (EDA), the EDR receptor (EDAR), the EDAR-associated death domain (EDARADD), the NF-kB signally pathway, which involves the NF-kB essential modulator and the transcription factor p63 [9]

The faulty regulation of the ectodermal development may, in some occasions, be followed by abnormalities of structures originating from the mesoderm or the endoderm.

Prevention

Ectodermal dysplasia is a group of inherited conditions and can therefore not be prevented. In families with a medical history of one of the conditions, direct genetic testing can be performed to determine the existence of this disease in an unborn child. A skin biopsy is also possible prenatally for the same reasons.

Summary

Ectodermal dysplasia is not a single condition, but refers to a group of inherited diseases whose common feature is the abnormal development of structures originating from the embryonic ectoderm. The defects affect the skin and any organ or structure attached to it, such as the hair follicles and, respectively, the hair, teeth, eccrine glands and nails. In order for the condition to be defined as ectodermal dysplasia, 2 or more structures must be involved and, depending on the particular clinical characteristics of each disease, nearly 200 congenital types have been described, which lead to anomalies of the ectodermal products. Except for the embryonic ectoderm, structures derived from the mesoderm or endoderm may be also be affected in some cases (ectodermal dysplasia syndromes). Patients displaying solely abnormalities related to the ectoderm are affected by pure ectodermal dysplasias.

Patient Information

The ectoderm is one of the three first cell layers to form in an embryo, and the most external layer of those three. As the embryo grows, various structures originate from this primitive cellular layer, such as the teeth, the skin, hair and sweat glands. Ectodermal dysplasia is a group of conditions with various characteristics which are all a result of a faulty development of the ectoderm. Thus, the appearance of the teeth, hair and nails are affected and the sweat glands are often sparse or absent.

Individuals affected by one of these conditions have fine, lightly-colored hair and frequently experience loss of their hair. Nails are distorted in appearance and the teeth are also irregularly shaped and may be less in number. People who have less sweat glands or no glands at all may experience frequent fevers: this happens due to the fact that the sweat produced by the body helps to keep the body's temperature from rising excessively.

the ectodermal dysplasia syndromes that that scientific community is familiar with until now are approximately 200. The conditions cannot be cured, but can be treated in order to manage the symptoms and offer the patients a better quality of life. In general, people affected by these conditions do not face other health problems, except for some rare cases.

References

Article

  1. 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;13 (4): 409-16. doi:10.1038/ng0895-409
  2. Pinheiro M, Freire-Maia N. The ectodermal dysplasias. Arch Dermatol. 1982 Apr. 118(4):215-6.
  3. 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.
  4. Freire-Maia N, Lisboa-Costa T, Pagnan NA. Ectodermal dysplasias: how many?. Am J Med Genet. 2001 Nov 15. 104(1):84.
  5. Lamartine J. Towards a new classification of ectodermal dysplasias. Clin Exp Dermatol. 2003 Jul. 28(4):351-5.
  6. Priolo M, Lagana C. Ectodermal dysplasias: a new clinical-genetic classification. J Med Genet. 2001 Sep. 38(9):579-85.
  7. 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.
  8. Motil KJ, Fete TJ, Fraley JK, et al. Growth characteristics of children with ectodermal dysplasia syndromes.Pediatrics. 2005 Aug. 116(2):e229-34.
  9. 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.
  10. Clouston HR. A hereditary ectodermal dystrophy. Can Med Assoc J. 1929. 21:18-31.
  11. Pierard GE, Van Neste D, Letot B. Hidrotic ectodermal dysplasia. Dermatologica. 1979. 158(3):168-74.
  12. 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.
  13. 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.
  14. 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.
  15. 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.

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Last updated: 2019-07-11 21:09