Ectodermal Dysplasia

שלום לכם זקוקה מאד למידע בעברית על המחלה . והאם יש לתסמונת שם עברי. בתודה מראש נשרקל

לנשרקל שלום רב, מצורף מדע באנגלית על המחלה. לצערי, לא מוכר לי מדע בעברית או שם של המחלה בעברית. Background: Ectodermal dysplasia syndrome (EDS) comprises a large, heterogeneous, nosologic group of inherited disorders that share primary defects in the development of 2 or more tissues derived from ectoderm. These tissues primarily are the skin, hair, nails, eccrine glands, and teeth. Defects in tissues derived from other embryologic layers are not uncommon. Current classification of ectodermal dysplasia (ED) is based on clinical features. Freire-Maia proposed classification into different subgroups according to presence or absence of the following: Trichodysplasia (subgroup 1) Dental abnormalities (subgroup 2) Onychodysplasia (subgroups 3) Dyshidrosis (subgroup 4) The disorders are congenital, diffusely present, and nonprogressive. To date, more than 150 distinctive syndromes have been described with all possible modes of inheritance. The most common syndromes within this group are (1) hypohidrotic (anhidrotic) ectodermal dysplasia, and (2) hidrotic ectodermal dysplasia. Several ED syndromes may present in association with midfacial defects, mainly cleft lip and palate. The following are the 3 most commonly recognized entities: EEC (ectodermal dysplasia, ectrodactyly, cleft lip/palate) syndrome Rapp-Hodgkin syndrome Hay-Wells or AEC (ankyloblepharon, ectodermal dysplasia, cleft lip/palate) syndrome Pathophysiology: ED results from abnormal morphogenesis of cuticular or oral derivatives from embryonal ectoderm. The number of hair follicles, sweat glands, and sebaceous glands varies. Reduction in hair follicles varies from sparse scalp hair (usually short, fine, dry) to complete absence. Structural hair-shaft abnormalities may result from aberrations in hair-bulb form and include longitudinal grooving, hair-shaft torsion, and cuticle ruffling. Hair bulbs may be distorted, bifid, and small. Eccrine sweat glands may be absent or sparse and rudimentary, particularly in hypohidrotic ectodermal dysplasia syndrome. In some cases, mucous glands are absent in the upper respiratory tract and in the bronchi, esophagus, and duodenum. The mouth may be dry from hypoplasia of salivary glands; lacrimal glands may also be deficient. Teeth show abnormal morphogenesis or are lacking. Nails are often brittle and thin or show abnormal ridging but may be grossly deformed. The presence or absence of these abnormalities defines the different syndromes. Frequency: In the US: Frequency of the different syndromes in a given population is highly dependent on phenotypic expression. Incidence of hypohidrotic ectodermal dysplasia is estimated to be 1:100,000 births. Internationally: Collectively, EDS frequency is estimated at 7:10,000 births. Mortality/Morbidity: Morbidity and mortality is related to absence or presence of eccrine and mucous glands. Beyond early childhood, life expectancy is normal to slightly reduced. Children with decreased sweating may suffer up to 30% mortality in infancy or early childhood due to intermittent hyperpyrexia. Pharyngitis, rhinitis, cheilitis, dysphagia, or diarrhea may follow reduced mucous glands in the respiratory and gastrointestinal tracts. Recurrent high fever may lead to seizures and neurological sequelae. Presence of severe scalp erosions or inflammation may cause scarring alopecia in the patients with AEC syndrome and Rapp-Hodgkin syndrome (less often). Race: ED syndromes have been reported most often in whites, but also have been observed in other races. Hidrotic ED has been reported in an extensive kindred of French extraction. Sex: X-linked hypohidrotic ectodermal dysplasia has full expression only in males. Female carriers outnumber affected men, but females show little or no signs of the condition. The remaining ED syndromes have no gender predilection. Age: All ED syndromes are present from birth. CLINICAL Section 3 of 11 Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography History: Individuals affected by EDS have abnormalities in different structures. Some EDS types are mild while others are devastating. Obvious manifestations of the disorders are not clinically apparent in newborns. Dental, hair, and nail anomalies are evident during infancy or childhood. Other signs and symptoms Lack of breast development Deficient tears and saliva Hearing or vision deficits Missing fingers or toes Cleft lip and/or palate Immune system problems Sensitivity to light Other ectoderm abnormalities Physical: Clinical appearance depends on the anomalies of each syndrome. Following are the best-defined syndromes within this group: Hypohidrotic (anhidrotic) ectodermal dysplasia (also known as Christ-Siemens-Touraine syndrome) is the most common phenotype in this group and usually is inherited as an X-linked recessive trait; autosomal recessive and autosomal dominant forms have been reported (rare). It is characterized by several defects (eg, hypohidrosis, anomalous dentition, onychodysplasia, hypotrichosis). Typical facies are characterized by frontal bossing; sunken cheeks; saddle-nose; thick, everted lips; wrinkled, hyperpigmented skin around the eyes; and large, low-set ears. Because such characteristics are not obvious at birth, clinical clues for diagnosis in the neonatal period are extensive scaling of the skin and unexplained pyrexia. Dental manifestations include conical or pegged teeth, hypodontia or complete anodontia, and delayed eruption of permanent teeth. Most patients are fair-haired, so little pigmentation in the hair shaft is observed microscopically and the medulla is often discontinuous. When medullation is present, a bar code appearance (similar to those used for electronic control) frequently is observed. Incidence of atopic eczema is high. Other common signs are short stature, eye abnormalities, decreased tearing, and photophobia. Intelligence is normal. Hidrotic ectodermal dysplasia (Clouston syndrome) is inherited as an autosomal dominant gene; the homozygous state may be lethal. Clinical features include nail dystrophy associated with hair defects and palmoplantar keratoderma. Nails are thickened and discolored; persistent paronychial infections are frequent. Scalp hair is very sparse, fine, and brittle. Eyebrows are thinned or absent. Patients have normal facies, no specific dental defect, and normal sweating. Biochemical abnormalities in keratin have been noted. Biochemical studies of keratin of hair in HED have shown decreased serine, proline and cystine while tyrosine and phenylalanine are increased. It has been postulated that a depletion of matrix proline and failure or disruption of some disulfide bonds are responsible for numerous structural abnormalities. Most frequent are variations in diameter and fracture or splitting of the cuticle. Rapp-Hodgkin ectodermal dysplasia is an autosomal dominant syndrome. High forehead, narrow nose, cleft lip or palate, and maxillary hyperplasia provide a distinctive facies. Hypohidrosis is severe enough to result in heat intolerance. Dental defects include conical teeth and hypodontia. Hair is sparse, has a steel-wool texture, and may show pili torti or pili canaliculi. Many cases present with recalcitrant, inflammatory scalp dermatitis followed by scarring alopecia. Nails are narrow and dystrophic. Occasional abnormalities include deafness, eye defects, and hypospadias. EEC syndrome is inherited as an autosomal dominant trait of low penetrance and variable expressivity. It is possibly autosomal recessive; many sporadic cases have been reported. Ectrodactyly, ectodermal dysplasia, and cleft lip and palate compose EEC syndrome. Ectrodactyly results in characteristic lobster-claw deformity of hands and feet. Cleft lip and palate create a characteristic nasal contour. Other ectodermal anomalies include occasional hypohidrosis, xerostomia, nail abnormalities, dental enamel hypoplasia, and microdontia. Associated defects are blepharophimosis or absent lacrimal puncta, strabismus, and abnormalities of the urinary tract. AEC syndrome (Hay-Wells syndrome) is inherited as an autosomal dominant trait of variable expressivity. Ankyloblepharon, ectodermal dysplasia, and cleft palate compose the syndrome. Characteristic facies is due to ankyloblepharon (congenital adhesion of the upper and lower eyelid margins by fibrous bands), broad nasal bridge, and sunken, hypoplastic maxilla. Cleft palate is frequent; cleft lip is rare. Hair may be sparse and coarse. Recalcitrant, crusted, inflammatory scalp dermatitis may cause scarring alopecia. Nails are absent or dystrophic; pointed teeth are common. Sweating is diminished. Other defects include lacrimal duct stenosis, microphthalmia, supernumerary nipples, syndactyly, and heart defects. Causes: EDS results from dyshistogenesis of ectodermal derivatives in early embryonic life. Genes responsible for the varied syndromes are located on different chromosomes and may be mutated or deleted. X-linked hypohidrotic ED has been mapped in the proximal area of the long arm of the chromosome band Xq-12-q13.1. A decreased expression of the epidermal growth factor receptor has been proposed as playing a causal role in this condition's phenotype. The gene ED1 responsible for the disorder has been identified as well as the analogous X-linked gene Ta in the mouse. Autosomal recessive disorders, phenotypically indistinguishable from the X-linked forms, exist in humans and at 2 separate loci (crinkled [cr], downless [dl]) in mice. Dominant disorders, possibly allelic to the recessive loci, are seen in both species. A candidate gene has recently been identified at the dl locus that is mutated. Two females with hypohidrotic ectodermal dysplasia with severe mental retardation have been reported. De novo X/9 and X/12 chromosome translocations were found. In both cases, the X chromosome breakpoint appears to be at Xq13.1. Different types of mutations at the same chromosomal locus and random X-chromosome inactivation (Lyon hypothesis) may explain the minimal expression in female carriers with hypohidrotic ED. Mutations in p63 gene are a major cause of EEC syndrome. A gene from chromosome 19 may act as a modifier gene by modulating the phenotypic outcome of p63 mutations. The gene that causes hidrotic ED (Clouston syndrome) has been identified to be GJB6, which encodes for connexin-30. GJB6 has been mapped to the pericentromeric region of chromosome 13q. Mutations of the gene PVRL1, encoding a cell-cell adhesion molecule/herpesvirus receptor, have been reported in cleft lip/palate-ectodermal dysplasia. בברכה ד"ר צופיה איש-שלום