Hypohidrotic ectodermal dysplasia is one of about 150 types of
ectodermal dysplasia in humans. Before birth, these disorders result in the abnormal development of structures including the
skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
,
hair, nails,
teeth
A tooth ( : teeth) is a hard, calcified structure found in the jaws (or mouths) of many vertebrates and used to break down food. Some animals, particularly carnivores and omnivores, also use teeth to help with capturing or wounding prey, te ...
, and
sweat gland
Sweat glands, also known as sudoriferous or sudoriparous glands, , are small tubular structures of the skin that produce sweat. Sweat glands are a type of exocrine gland, which are glands that produce and secrete substances onto an epithelial s ...
s.
[Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. .]
Presentation
Most people with hypohidrotic ectodermal dysplasia have a reduced ability to sweat (
hypohidrosis
Hypohidrosis is a disorder in which a person exhibits diminished sweating in response to appropriate stimuli. In contrast with hyp''er''hidrosis, which is a socially troubling yet often benign condition, the consequences of untreated hypohidros ...
) because they have fewer sweat glands than normal or their sweat glands do not function properly. Sweating is a major way that the body controls its temperature; as sweat evaporates from the skin, it cools the body. An inability to sweat can lead to a dangerously high body temperature (
hyperthermia
Hyperthermia, also known simply as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme ...
) particularly in hot weather. In some cases, hyperthermia can cause life-threatening medical problems.
Affected individuals tend to have sparse scalp and body hair (
hypotrichosis
Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarr ...
). The hair is often light-coloured, brittle, and slow-growing. This condition is also characterized by absent teeth (
hypodontia) or teeth that are malformed. The teeth that are present are frequently small and pointed.
Hypohidrotic ectodermal dysplasia is associated with distinctive facial features including a prominent forehead, thin lips, and a flattened bridge of the nose. Additional features of this condition include thin, wrinkled, and dark-colored skin around the eyes; chronic skin problems such as
eczema; and a foul-smelling discharge from the nose (
ozena
Chronic atrophic rhinitis, or simply atrophic rhinitis, is a chronic inflammation of the Human nose, nose characterised by atrophy of Mucus, nasal mucosa, including the glands, turbinate bones and the nerve elements supplying the nose. Chronic a ...
). Hypohidrotic ectodermal dysplasia is the most common form of ectodermal dysplasia in humans. It is estimated to affect at least 1 in 17,000 people worldwide.
Genetics
Mutations in the ''
EDA'', ''
EDAR'', and ''
EDARADD
Ectodysplasin-A receptor-associated adapter protein is a protein that in humans is encoded by the ''EDARADD'' gene.
Function
This gene was identified by its association with ectodermal dysplasia, and specifically with hypohidrotic ectodermal d ...
'' genes cause hypohidrotic ectodermal dysplasia. The ''EDA'', ''EDAR'', and ''EDARADD'' genes provide instructions for making proteins that work together during embryonic development. These proteins form part of a signaling pathway that is critical for the interaction between two cell layers, the ectoderm and the
mesoderm. In the early embryo, these cell layers form the basis for many of the body's organs and tissues. 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.
Hypohidrotic ectodermal dysplasia has several different inheritance patterns.
EDA (X-linked)
Most cases are caused by mutations in the EDA gene, which are inherited in an
X-linked recessive
X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be always expressed in males (who are necessarily homozygous for the gene mutation because they have one X and one ...
pattern, called x-linked hypohidrotic ectodermal dysplasia (XLHED). A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. 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. If a female carrier is operating on her normal X she will not show symptoms. If a female is operating on her carrier X she will show symptoms. In about 70 percent of cases, carriers of hypohidrotic ectodermal dysplasia experience some features of the condition. These signs and symptoms are usually mild and include a few missing or abnormal teeth, sparse hair, and some problems with sweat gland function. Some carriers, however, have more severe features of this disorder.
Treatments
In January 2013, Edimer Pharmaceuticals, a biotechnology company based in Cambridge, MA, USA, initiated a Phase I, open-label, safety and pharmacokineti
clinical studyo
EDI200 a drug aimed at the treatment of XLHED. 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. 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. As the treated group "didn’t see significant changes in sweat gland function and other early markers of biologic activity", prenatal administration of the drug was considered.
Following the Edimer trials, Dr. Holm Schneider, the principal investigator of these trials which indicated sufficient safety of the replacement protein, 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.
EDAR or EDARADD (autosomal)
Less commonly, hypohidrotic ectodermal dysplasia results from mutations in the EDAR or EDARADD gene. Both EDAR and EDARADD mutations can have an autosomal dominant or autosomal recessive pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Autosomal recessive inheritance means two copies of the gene in each cell are altered. 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.
Terminology
The eponym Christ-Siemens-Touraine syndrome was named after its discoverers: Josef Christ (1871–1948), a German dentist and physician from
Wiesbaden
Wiesbaden () is a city in central western Germany and the capital of the state of Hesse. , it had 290,955 inhabitants, plus approximately 21,000 United States citizens (mostly associated with the United States Army). The Wiesbaden urban area ...
, who was the first physician to identify the condition,
Hermann Werner Siemens (1891–1969), a pioneering German dermatologist from
Charlottenburg, who clearly identified its pathological characteristics in the early 1930s, and
Albert Touraine (1883–1961), a French dermatologist who likewise noted and identified additional characteristics of the disease in the late 1930s.
Notable individuals
*
Michael Berryman
Michael John Berryman (born September 4, 1948) is an American character actor. Berryman was born with hypohidrotic ectodermal dysplasia, a rare condition characterized by the absence of sweat glands, hair, and fingernails; his unusual physical ...
,
Saturn Award
The Saturn Awards are American awards presented annually by the Academy of Science Fiction, Fantasy and Horror Films. The awards were created to honor science fiction, fantasy, and horror in film, but have since grown to reward other films bel ...
-nominated
character actor
See also
*
Hermann Werner Siemens
*
List of cutaneous conditions
Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier agai ...
*
Albert Touraine
*
List of radiographic findings associated with cutaneous conditions
*
References
External links
GeneReview/NIH/UW entry on Hypohidrotic Ectodermal Dysplasia*
{{Extracellular ligand disorders
Genodermatoses
Defects in innate immunity
Ectoderm
Syndromes
Rare diseases