| Hypohidrotic ectodermal dysplasia | |
|---|---|
| Other names | Anhidrotic ectodermal dysplasia, Christ-Siemens-Touraine syndrome [1] : 570 |
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| This condition is inherited in an X-linked recessive manner. | |
| Specialty | Medical genetics  |
Hypohidrotic ectodermal dysplasia is one of about 150 types of ectodermal dysplasia in humans. These disorders result in the development of structures including the skin where people sweat less. [2]
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. Sweating is a major way that the body controls its temperature; as sweat evaporates from the skin, it cools the body.
The hair is often light-coloured, brittle, and slow-growing. This condition is also characterized by absent teeth (hypodontia) or teeth that are malformed.
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.[ citation needed ]
Mutations in the EDA , EDAR , and EDARADD 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.[ citation needed ]
Hypohidrotic ectodermal dysplasia has several different inheritance patterns.
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). 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.[ citation needed ]
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.
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. 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. [3] As the treated group "didn’t see significant changes in sweat gland function and other early markers of biologic activity", [4] 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, [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. [6] [7]
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.[ citation needed ]
Thurnam in 1848 reported 2 cases of hypohidrotic form. Similar cases were reported by Guilford and Hutchinson in 1883 and 1886 respectively. Weech, in 1929 introduced the term hereditary ectodermal dysplasia and suggested the term anhidrotic for those with inability to perspire.
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders are the most common, the term is mostly used when discussing disorders with a single genetic cause, either in a gene or chromosome. The mutation responsible can occur spontaneously before embryonic development, or it can be inherited from two parents who are carriers of a faulty gene or from a parent with the disorder. When the genetic disorder is inherited from one or both parents, it is also classified as a hereditary disease. Some disorders are caused by a mutation on the X chromosome and have X-linked inheritance. Very few disorders are inherited on the Y chromosome or mitochondrial DNA.
The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm and endoderm. It emerges and originates from the outer layer of germ cells. The word ectoderm comes from the Greek ektos meaning "outside", and derma meaning "skin".
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 and in females who are homozygous for the gene mutation, see zygosity. Females with one copy of the mutated gene are carriers.
Ectodermal dysplasia (ED) is a group of genetic syndromes all deriving from abnormalities of the ectodermal structures. More than 150 different syndromes have been identified.
Meleda disease (MDM) or "mal de Meleda", also called Mljet disease, keratosis palmoplantaris and transgradiens of Siemens, is an extremely rare autosomal recessive congenital skin disorder in which dry, thick patches of skin develop on the soles of the hands and feet, a condition known as palmoplantar hyperkeratosis. Meleda Disease is a skin condition which usually can be identified not long after birth. This is a genetic condition but it is very rare. The hands and feet usually are the first to show signs of the disease but the disease can advance to other parts of the body. Signs of the disease include thickening of the skin, on hands and soles of feet, which can turn red in color. There currently is no cure and treatment is limited, but Acitretin can be used in severe cases.
3-Methylglutaconic aciduria (MGA) is any of at least five metabolic disorders that impair the body's ability to make energy in the mitochondria. As a result of this impairment, 3-methylglutaconic acid and 3-methylglutaric acid build up and can be detected in the urine.
Autosomal recessive multiple epiphyseal dysplasia (ARMED), also called epiphyseal dysplasia, multiple, 4 (EDM4), multiple epiphyseal dysplasia with clubfoot or –with bilayered patellae, is an autosomal recessive congenital disorder affecting cartilage and bone development. The disorder has relatively mild signs and symptoms, including joint pain, scoliosis, and malformations of the hands, feet, and knees.
Ectrodactyly–ectodermal dysplasia–cleft syndrome, or EEC, and also referred to as EEC syndrome and split hand–split foot–ectodermal dysplasia–cleft syndrome is a rare form of ectodermal dysplasia, an autosomal dominant disorder inherited as a genetic trait. EEC is characterized by the triad of ectrodactyly, ectodermal dysplasia, and facial clefts. Other features noted in association with EEC include vesicoureteral reflux, recurrent urinary tract infections, obstruction of the nasolacrimal duct, decreased pigmentation of the hair and skin, missing or abnormal teeth, enamel hypoplasia, absent punctae in the lower eyelids, photophobia, occasional cognitive impairment and kidney anomalies, and conductive hearing loss.
Amastia refers to a rare clinical anomaly in which both internal breast tissue and the visible nipple are absent on one or both sides. It affects both men and women. Amastia can be either isolated or comorbid with other syndromes, such as ectodermal dysplasia, Syndactyly and lipoatrophic diabetes. This abnormality can be classified into various types, and each could result from different pathologies. Amastia differs from amazia and athelia. Amazia is the absence of one or both mammary glands but the nipples remain present, and athelia is the absence of one or both nipples, but the mammary gland remains.
Naegeli–Franceschetti–Jadassohn syndrome (NFJS), also known as chromatophore nevus of Naegeli and Naegeli syndrome, is a rare autosomal dominant form of ectodermal dysplasia, characterized by reticular skin pigmentation, diminished function of the sweat glands, the absence of teeth and hyperkeratosis of the palms and soles. One of the most striking features is the absence of fingerprint lines on the fingers.
Hay–Wells syndrome is one of at least 150 known types of ectodermal dysplasia. These disorders affect tissues that arise from the ectodermal germ layer, such as skin, hair, and nails.
Rosselli–Gulienetti syndrome, also known as Zlotogora–Ogur syndrome and Bowen–Armstrong syndrome, is a type of congenital ectodermal dysplasia syndrome. The syndrome is relatively rare and has only been described in a few cases.
Uncombable hair syndrome (UHS) is a rare structural anomaly of the hair with a variable degree of effect. It is characterized by hair that is silvery, dry, frizzy, wiry, and impossible to comb. It was first reported in the early 20th century. It typically becomes apparent between the ages of 3 months and 12 years. UHS has several names, including pili trianguli et canaliculi (Latin), cheveux incoiffables (French), and "spun-glass hair". This disorder is believed to be autosomal recessive in most instances, but there are a few documented cases where multiple family members display the trait in an autosomal dominant fashion. Based on the current scientific studies related to the disorder, the three genes that have been causally linked to UHS are PADI3, TGM3, and TCHH. These genes encode proteins important for hair shaft formation. Clinical symptoms of the disorder arise between 3 months and 12 years of age. The quantity of hair on the head does not change, but hair starts to grow more slowly and becomes increasingly "uncombable". To be clinically apparent, 50% of all scalp hair shafts must be affected by UHS. This syndrome only affects the hair shaft of the scalp and does not influence hair growth in terms of quantity, textural feel, or appearance on the rest of the body.
Ectodysplasin A (EDA) is a protein that in humans is encoded by the EDA gene.
Ectodysplasin A receptor (EDAR) is a protein that in humans is encoded by the EDAR gene. EDAR is a cell surface receptor for ectodysplasin A which plays an important role in the development of ectodermal tissues such as the skin. It is structurally related to members of the TNF receptor superfamily.
Ectodysplasin-A receptor-associated adapter protein is a protein that in humans is encoded by the EDARADD gene.
EEM syndrome is an autosomal recessive congenital malformation disorder affecting tissues associated with the ectoderm, and also the hands, feet and eyes.
ANOTHER syndrome consists of alopecia, nail dystrophy, ophthalmic complications, thyroid dysfunction, hypohidrosis, ephelides and enteropathy, and respiratory tract infections. This is an Autosomal recessive variant of ectodermal dysplasia.
Odontoonychodermal dysplasia is a rare genetic disorder which is characterized by systemic abnormalities of the teeth, the nails of the fingers and toes, the skin, the hair cells, and the sweat glands. It is a type of syndromic ectodermal dysplasia.
Hypohidrotic/anhidrotic ectodermal dysplasia with immune deficiency is a rare genetic condition characterized by a combination of the features of ectodermal dysplasia alongside immunodeficiency.