hypohidrotic ectodermal dysplasia symptoms
If possible, it is recommended that individuals with HED live in a cool climate. Additional symptoms and findings often include fine, sparse, abnormally light (hypopigmented) scalp hair and eyebrows; absent eyelashes; and/or abnormalities of the tear (lacrimal) ducts that may cause abnormal tearing, increased susceptibility to eye infections, and chronic inflammation of the delicate membranes that line the inside of the eyelids (conjunctivitis), potentially causing visual impairment. The hair is often light-coloured, brittle, and slow-growing. Entry No: 129500; Last Update: 11/13/2012. If a female carrier is operating on her normal X she will not show symptoms. Physicians may also regularly monitor affected infants and children to help prevent respiratory infections and to ensure prompt, aggressive treatment should such infections occur. Davis JR, et al. For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office: For information about clinical trials sponsored by private sources, contact: For information about clinical trials conducted in Europe, contact: (Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., dysplasia-associated characteristics of the skin, hair, and teeth; mental retardation; etc.].). Most cases are caused by mutations in the EDA gene, which are inherited in an X-linked recessive pattern, called x-linked hypohidrotic ectodermal dysplasia (XLHED). Sweating is a major way that the body controls its temperature; as sweat evaporates from the skin, it cools the body. Pediatr Dermatol. Philadelphia, PA: W. B. Saunders Co: 1997:540-41. Join us online to meet medical and dental experts and have the unique opportunity to talk with them one-on-one to ask questions. Also known as the vampire disorder, people who suffer from Hypohidrotic ectodermal dysplasia often have pointed teeth, making them look eerily similar to the blood-sucking creatures of fiction. [2]:515–517, Most people with hypohidrotic ectodermal dysplasia have a reduced ability to sweat (hypohidrosis) because they have fewer sweat glands than normal or their sweat glands do not function properly. Curr Probl Dermatol. Individuals with such disorders usually have characteristic abnormalities not typically associated with HED. Hidrotic ectodermal dysplasia (Clouston type) is inherited as an autosomal dominant genetic trait. A few of these disorders include: Schopf-Schulz-Passarge syndrome, odonto-onycho-dermal dysplasia syndrome, Witkop tooth and nail syndrome, and tricho-dento-osseous syndrome. Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. In affected males and females, pubic and underarm (axillary) hair is typically scant. Behrman RE, ed. Additionally there may be abnormalities in the skin ridge patterns (dermatoglyphic patterns) on the fingers, toes, palms of the hands, and/or soles of the feet. HED is primarily characterized by partial or complete absence of certain sweat glands (eccrine glands), causing lack of or diminished sweating (anhidrosis or hypohidrosis), heat intolerance, and fever; abnormally sparse hair (hypotrichosis), and absence (hypodontia) and/or malformation of certain teeth. NORD gratefully acknowledges Jing Wang, NORD Editorial Intern from the University of Notre Dame, and J Timothy Wright, DDS, MS, Distinguished Bawden Professor, Department of Pediatric Dentistry, University of North Carolina, for assistance in the preparation of this report. In: Pagon RA, Adam MP, Bird TD, et al., editors. Disorder of the differentiation of hair follicles and sweat glands leads to abnormal keratinization. J Med Genet. Some carriers, however, have more severe features of this disorder. Hautarzt. A mutation in the EDAR gene can have an autosomal dominant or autosomal recessive pattern of inheritance, while a mutation in the EDARADD gene has an autosomal recessive pattern of inheritance. HED is characterized by lack of or diminished sweating (anhidrosis or hypohidrosis), abnormally sparse hair (hypotrichosis), and/or absence (hypodontia) and/or malformation of certain teeth. The treatment of HED is directed toward the specific symptoms that are apparent in each individual. Additional diagnostic tools are available and may include a test in which the sweat glands are stimulated by a drug called pilocarpine through the use of direct current (iontophoresis) and the resulting perspiration is measured and analyzed. Nat Genet. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder. [citation needed], Affected individuals tend to have sparse scalp and body hair (hypotrichosis). Stephen D. Campbell, Lyndon Cooper, Helen Craddock, T. Paul Hyde, Brian Nattress, Sue H. Pavitt, David W. Seymour [citation needed], Hypohidrotic ectodermal dysplasia is associated with distinctive facial features including a prominent forehead, thick lips, and a flattened bridge of the nose. Hypohidrotic ectodermal dysplasia. Some individuals with the disorder have unusually thin and brittle nails. Champion RH, et al., eds. Semin Dermatol. Because the vast majority of cases of HED are thought to be X-linked, it is suspected that approximately 90 percent of affected individuals are male. This form of ectodermal dysplasia is considered “hidrotic” due to the absence of abnormalities affecting the sweat glands. If we don't have a program for you now, please continue to check back with us. ), The ectodermal dysplasias are a group of more than 150 related disorders that result from abnormalities during early embryonic development. This page was last edited on 21 November 2020, at 18:45. HED is thought to occur in approximately 1 in 5,000-10,000 newborns. Seattle (WA): University of Washington, Seattle; 1993-2013. HED is usually inherited as an X-linked recessive genetic trait and is caused by a mutation in the ectodysplasin-A (EDA) gene; in such cases, the disorder is fully expressed in males only. Abnormal bald patches on the scalp (alopecia) may also be present. Hum Genet. In males and females with the autosomal recessive form of HED, such a count will also reveal decreased number of sweat pores. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. In some cases, hyperthermia can cause life-threatening medical problems. However, the skin around the eyes (periorbital) may be darkly pigmented (hyperpigmentation) and finely wrinkled, appearing prematurely aged. To search for patient organizations and other pages related to this topic, use the Advanced Search function at the top right corner of the page. J Clin Pediatr Dent. NORD strives to open new assistance programs as funding allows. Ectoderm-mesoderm interactions are essential for the formation of several structures that arise from the ectoderm, including the skin, hair, nails, teeth, and sweat glands. Baltimore. HED can also be inherited as an autosomal dominant or autosomal recessive genetic trait, caused by mutations in the EDAR or EDARADD genes. There are a variety of problems associated with tooth disorders such as cavities and infections. Treatment may require the coordinated efforts of a team of specialists who need to systematically and comprehensively plan an affected individual's treatment. In the early embryo, these cell layers form the basis for many of the body's organs and tissues. : 515–517 Hypohidrotic ectodermal dysplasia has several different inheritance patterns. Scalp hair is usually blond or lightly pigmented; abnormally sparse, short, and fine; and, in some cases, stiff, dry, and unruly. Such specialists may include pediatricians or internists, physicians who treat disorders of the skin (dermatologists), dental specialists, physicians who diagnose and treat disorders of the ears, nose, and throat (otolaryngologists), allergists, and/or other health care professionals. Online Mendelian Inheritance in Man (OMIM). Cambridge, MA: Blackwell Scientific Publications; 1992:335-37. Entry No: 224900; Last Update: 11/20/2012. There are several rare HED forms or subtypes that have abnormally decreased function of certain components of the immune system (e.g., depressed lymphocyte function, cellular immune hypofunction). 1991;28:181-85. 1994;45:378-84. In individuals with hidrotic ectodermal dysplasia (Clouston Type), physical features may include abnormally developed (dysplastic), underdeveloped (hypoplastic), or absent (aplastic) nails; scanty eyebrows, eyelashes, and body hair (hypotrichosis) with abnormally thin, sparse scalp hair or baldness; and/or, in some cases, abnormally thick, rough skin on the palms of the hands and the soles of the feet (palmoplantar keratoderma). These may include absence and/or malformation of certain teeth, sparse hair, and/or reduced sweating. In most cases, the teeth that are present are widely spaced, with front teeth being pointed or cone shaped. In most cases, HED is diagnosed during early childhood when characteristic dental and hair abnormalities become apparent and prompt further testing. Ectodermal dysplasias typically affect the hair, teeth, nails, sweat glands, and/or skin. Another method frequently used is the counting of sweat pores by direct observation. In many individuals with HED, mucous glands within the membrane lining the respiratory and gastrointestinal (GI) tracts (e.g., in the lung, pharynx, larynx, trachea, upper esophagus, stomach, intestines) are underdeveloped (hypoplastic) or absent (aplastic). Am J Phys Anthropol. Comment in: Nat Genet. One such test that is particularly helpful in detecting females who carry a single copy of the disease gene for X-linked HED (heterozygotes) consists of the application of an iodine-in-alcohol solution over the entire back, followed by the application of a corn starch/castor oil suspension. Following the Edimer trials, Dr. Holm Schneider, the principal investigator of these trials which indicated sufficient safety of the replacement protein,[5] injected EDI200 via amniocentesis with better development of tooth buds and sweat glands than in the postnatal trial and persistent sweating ability in all three treated boys. National Organization for Rare Disorders (NORD) 55 Kenosia Ave., Danbury CT 06810 • (203)744-0100. Autosomal recessive inheritance means two copies of the gene in each cell are altered. Researchers also have reported cases in which HED appears to be inherited as an autosomal dominant or recessive genetic trait, but these patterns of inheritance are less common. Clinical and radiographic dental findings in X linked hypohidrotic ectodermal dysplasia. Although some symptoms and findings associated with the disorder are present shortly after birth such as heat intolerance, unexplained fever, and/or extensive peeling of the skin, the characteristic facial abnormalities may not be apparent in affected infants. 2001;25:303-10. A second trial in newborn infants with XLHED tested the synthetic protein in 10 subjects between 2013 and 2016 at 6 sites in the US and Europe. 1996;13:409-16. J Med Genet. However, females who carry a single copy of the disease gene (heterozygote carriers) may exhibit some of the symptoms and findings associated with the disorder. It also facilitates cell membrane function and proper enzyme activity. The range and severity of symptoms and physical findings associated with the disorder vary widely from case to case. An inherited condition called hypohidrotic ectodermal dysplasia causes people to be born with either very few or no sweat glands. Coll Antropol. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Saunders Company; 1996:1837. The ectodermal germ cell layer normally forms the nervous system, tooth enamel, epidermis of the skin, lining of the mouth, anus, nose, sweat glands, hair, and nails, but a mutated EDA gene will disrupt the normal function of a number of these characteristics. The teeth most often present include front teeth (central incisors), teeth normally located next to the incisors (canines), and/or, in some cases, one or more molars. In addition, due to hypodontia, the lips may protrude outward (everted) and appear abnormally thick, the gums may be abnormally small or degenerated (atrophic), and the normally exposed red portion of the upper and lower lips (vermilion border) may not be noticeable. If both parents carry the same disease gene, there is a higher than normal risk that their children may inherit the two genes necessary for the development of the disease. 1993;12:241-46. Last update: December 2012. Hypohidrotic Ectodermal Dysplasia. Many affected infants and children experience recurrent attacks of wheezing and breathlessness (asthma), respiratory infections; chronic inflammation of the nasal passages (atrophic rhinitis), scaling, itchy (pruritic) skin rashes (eczema), and/or other findings. EEC syndrome, also known as ectrodactyly-ectodermal dysplasia-cleft lip/palate, is a rare genetic disorder that may be characterized by absence of all or a portion of one or more fingers and/or toes (ectrodactyly) or other digital malformations; incomplete closure of the roof of the mouth (cleft palate) and an abnormal groove in the upper lip (cleft lip); and/or other characteristic abnormalities. Salivary glands can also be underdeveloped (hypoplastic), leading to abnormal dryness of the mouth and an altered sense of taste or smell. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. [citation needed]. An inability to sweat can lead to a dangerously high body temperature (hyperthermia) particularly in hot weather. Use of morphological markers in carriers as an aid in genetic counseling and prenatal diagnosis. James, William; Berger, Timothy; Elston, Dirk (2005). Because affected infants and children are unable to sweat appropriately when exposed to warm environments, they can experience repeated episodes of heat intolerance and “unexplained” high fevers that may remain unexplained until the disorder is diagnosed. In addition, the eyebrows and eyelashes are often scanty or absent, although, in some cases, the eyelashes may appear normal. Other treatment is symptomatic and supportive. [citation needed], Mutations in the EDA, EDAR, and EDARADD genes cause hypohidrotic ectodermal dysplasia. During development in mice and dogs EDI200 has been shown to substitute for the altered or missing protein resulting from the EDA mutation which causes XLHED. These signs and symptoms are usually mild and include a few missing or abnormal teeth, sparse hair, and some problems with sweat gland function. Prenatal diagnosis of X-linked hypohidrotic ectodermal dysplasia by linkage analysis. Jones KL, ed. 5th ed. NORD is not a medical provider or health care facility and thus can neither diagnose any disease or disorder nor endorse or recommend any specific medical treatments. Uncover the related symptoms, such as a toothache. If a female is operating on her carrier X she will show symptoms. Therefore, the disorder often is not recognized in affected infants and children until associated dental and hair abnormalities become apparent. Birth Defects Orig Artic Ser. This condition is also characterized by absent teeth (hypodontia) or teeth that are malformed. In addition, some individuals with HED are unable to produce tears due to underdevelopment of the glands that secrete tears (hypoplastic lacrimal glands), hypoplasia of the ducts through which the tears pass (lacrimal ducts), and/or abnormal narrowing of the small openings in the inner corners of the eyelids where tears normally drain (stenotic lacrimal puncta). Artificial teeth and/or other devices (prosthetics) may be used to replace absent teeth. Syndromes of the Head and Neck, 3rd ed. For example, hypohidrotic ectodermal dysplasia affects the hair, teeth and sweat glands while Clouston syndrome affects the hair and nails. (For more information on these disorders, choose “ectodermal dysplasia” or the exact disease name in question as your search term in the Rare Disease Database.). Accessed Jan 8, 2014. In cases of X-linked HED, direct observation reveals no sweat pores in affected males and decreased numbers of sweat pores in female carriers. Please note that NORD provides this information for the benefit of the rare disease community. In some cases, application of the substance o-phthalaldehyde may be applied directly to the skin (topically) of the palm. Comparisons may be useful for a differential diagnosis: Hidrotic ectodermal dysplasia (Clouston type), one of the group of disorders classified as ectodermal dysplasias, is characterized by abnormalities involving the nails, hair, skin, and/or teeth. Ectodermal dysplasia (ED) is a group of genetic syndromes all deriving from abnormalities of the ectodermal structures. Additional features of this condition include thin, wrinkled, and dark-colored skin around the eyes; chronic skin problems such as eczema; and a bad-smelling discharge from the nose (ozena).Hypohidrotic ectodermal dysplasia is the most common form of ectodermal dysplasia in humans. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1112/ Accessed Jan 8, 2014. As a result of missing teeth the bony ridge of the jaws (alveolar process) that holds the teeth in place often fails to form properly. This disorder can also affect hair, skin, and nails. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:597-98, 600-01, 607-08. Female carriers of X-linked HED may have dental abnormalities such as absence of certain teeth (hypodontia) and/or abnormally small, pointed, conical teeth; sparse hair (hypotrichosis); reduced sweating; and/or irregular dermatoglyphic patterns. Some individuals can be missing all the teeth in one jaw and have some in the other jaw. [6][7], Less commonly, hypohidrotic ectodermal dysplasia results from mutations in the EDAR or EDARADD gene. Abnormal sparseness of hair (hypotrichosis) is also a primary characteristic of HED, and is due to incomplete formation and reduced numbers of hair follicles. Kere J, et al. The teeth that are present are frequently small and pointed. In addition, affected individuals often have characteristic facial abnormalities, irregularities of the skin, abnormalities of the mucous membranes lining the respiratory and gastrointestinal (GI) tracts, an increased tendency to develop certain infections and allergic conditions, and/or other abnormalities. Am J Med Genet. Many individuals with HED have additional, characteristic facial features, including a prominent forehead (frontal bossing); underdeveloped nostrils (hypoplastic alae nasi) and a low or sunken nasal bridge (so-called “saddle nose”); and underdeveloped, sunken cheeks (malar hypoplasia). Specialized diagnostic testing may include microscopic examination of small samples of skin tissue removed from the palm, confirming partial or complete absence of eccrine sweat glands. Glavina D, et al. Despite some of the syndromes having different genetic causes, the symptoms are sometimes very similar. McKusick VA, ed. Women who are carriers of an X-linked disorder have a 50 percent risk of transmitting the carrier condition to their daughters, and a 50 percent risk of transmitting the disease to their sons. Before birth, these disorders result in the abnormal development of structures including the skin, hair, nails, teeth, and sweat glands. Ward RE, et al. Thus, in summary, when HED is inherited as an X-linked recessive trait, the disorder is fully expressed in males only and it is transmitted through the maternal X chromosome. Anhidrotic ectodermal dysplasia. Molecular testing for mutations in the EDA, EDAR, and EDARADD genes is available to confirm the diagnosis. The range and severity of the symptoms and findings associated with HED varies from case to case. In some cases, hair may be absent from the arms, legs, and/or trunk. Since females operate on only one of their two X chromosomes (X inactivation) a female carrier may or may not manifest symptoms of the disease. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In addition, dental x-rays to verify the absence of certain teeth and to further characterize associated dental abnormalities play an essential role in helping to confirm a diagnosis of HED or identify carrier status. The immune system works to protect the body against invading microorganisms, toxins, and other substances that are recognized as foreign to the body. Approximately 70% of female carriers show symptoms that are typically milder than those associated with the fully expressed disorder. The protein regulated (encoded) by this gene is a type II membrane protein that acts as a homotrimer (a protein with three identical units of polypeptide) and may be involved in cell-cell signaling during early embryonic development when ectodermal organs are beginning to be formed. [citation needed], see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder, EDAR (EDAR hypohidrotic ectodermal dysplasia), Deficiencies of intracellular signaling peptides and proteins. MD: The Johns Hopkins University. In many cases, additional symptoms and findings may be associated with EEC syndrome including absence of the mucous membrane normally lining the voice box (larynx), causing abnormal breathiness of the voice; abnormalities of the urinary tract; deafness; and/or other abnormalities. In January 2013, Edimer Pharmaceuticals, a biotechnology company based in Cambridge, MA, USA, initiated a Phase I, open-label, safety and pharmacokinetic clinical study of EDI200, a drug aimed at the treatment of XLHED. Many individuals with HED also have characteristic facial abnormalities including a prominent forehead, a sunken nasal bridge (so-called "saddle nose"), unusually thick lips, and/or a large chin. What are the symptoms of hypohidrosis? In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Blanchet-Bardon C, et al. In some cases, other types of sweat testing may be used to determine the reduction or absence of perspiration. Nelson Textbook of Pediatrics, 15th ed. Symptoms of the following disorders may be similar to those of hypohidrotic ectodermal dysplasia. In such cases, the disorder is fully expressed in both males and females. In the majority of individuals with HED, the skin on most of the body is unusually thin and soft and can lack normal pigmentation (hypopigmentation). Arnold ML, et al. Characterization of the face in hypohidrotic ectodermal dysplasia by cephalometric and anthropometric analysis. Females who carry a single copy of the mutated EDA gene for X-linked HED (heterozygote carriers) may have no symptoms or physical abnormalities or may have some of the characteristics associated with the disease. Many affected newborns have unusual scaling or peeling of the skin, while many children develop itchy (pruritic), scaling skin rashes (eczema). New York, NY: Oxford University Press; 1990:451-56. Such diagnosis is based upon a thorough clinical evaluation, identification of characteristic physical findings, a detailed patient and family history, and specialized laboratory testing. Gorlin RJ, et al., eds. As a result, in such cases, some females exhibit some of the symptoms associated with the disorder. This condition is inherited in an X-linked recessive manner. Eating hot foods may also cause extreme discomfort. There are additional disorders that may be characterized by dental abnormalities, hypotrichosis, skin irregularities, craniofacial abnormalities, and/or other symptoms and findings similar to those associated with HED. Yet, most types share some common symptoms, ranging from mild to severe. Autosomal recessive inheritance means two copies of the gene in each cell are altered. 1989;6:76-81. EEC syndrome is thought to be inherited as an autosomal dominant genetic trait. Cellular immunodeficiency in anhidrotic ectodermal dysplasia. Patients must rely on the personal and individualized medical advice of their qualified health care professionals before seeking any information related to their particular diagnosis, cure or treatment of a condition or disorder. After puberty, male patterns of hair growth (e.g., moustache and beard) can be normal, while in other cases, facial and pubic hair growth may be sparse. In some cases, during the newborn period, heat intolerance, unexplained fevers, and/or extensive skin peeling may lead to an earlier diagnosis. In affected individuals with impaired tear secretion (alacrima), the use of artificial tears may help to prevent possible corneal damage. The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. The National Foundation for Ectodermal Dysplasias is offering many of our Family Conference sessions virtually in 2021 until it’s safe for us to meet in person again. Blume-Peytavi U, et al. Acta Derm Venereol. 1990;27:422-25. 1987;62:989-96. X-linked recessive disorders are conditions that are coded on the X chromosome. Potassium, a necessary electrolyte, facilitates nerve impulse conduction and the contraction of skeletal and smooth muscles, including the heart. The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Goodship J, et al. Males are affected by X-linked recessive disorders much more frequently than females. 2001;26:5-12. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. However, the skin around the eyes (periorbital) may be darkly pigmented (hyperpigmentation) and finely wrinkled, appearing prematurely aged. More than 100 different types of ectodermal dysplasias exist. 5 Hypohidrotic Ectodermal Dysplasia. 1996;13:379-80. In some rare cases, individuals with HED may lack all upper and/or lower teeth (edentulous or anodontia). Probably the most well-known type of dysplasia is a cervical dysplasia.This is dysplasia of the cervix, which is the lower portion of … Available at http://www.ncbi.nlm.nih.gov/omim Entry No: 305100; Last Update: 01/08/13. In many cases, affected infants and children may also exhibit underdevelopment (hypoplasia) or absence (aplasia) of mucous glands within the respiratory and gastrointestinal (GI) tracts and, in some cases, decreased function of certain components of the immune system (e.g., depressed lymphocyte function, and rarely cellular immune hypofunction), potentially causing an increased susceptibility to certain infections and/or allergic conditions. In some females who inherit a single copy of the disease gene (heterozygote carriers) for HED, the disease may not be “masked” by the normal gene on the other X chromosome. Hypohidrotic ectodermal dysplasia.