Ala88Val pathogenic variants can be associated with a clinical picture similar to that of pachyonychia congenita [van Steensel et al ] (see. CAPÍTULO Displasia ectodérmica hidrótica. Sections; Print; Share . ), disqueratosis congénita, paquioniquia congénita (fig. ), síndrome de. Differential diagnosis. The differential diagnosis should include pachyonychia congenita and other forms of ectodermal dysplasia (see these terms).
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University of Washington, Seattle; April 25, ; Last Update: Hidrotic ectodermal dysplasia 2, or Clouston syndrome referred to as HED2 throughout this GeneReview is characterized by partial or total alopecia, dystrophy of the nails, hyperpigmentation of the skin especially over the jointsand clubbing of the ectldermica.
Sparse scalp hair and dysplastic nails are seen early in life. In infancy, scalp hair is wiry, brittle, patchy, and pale; progressive hair loss may lead to total alopecia by puberty.
The nails may be milky white in early childhood; they gradually become dystrophic, thick, congenitw distally separated from the nail displaaia. Palmoplantar keratoderma may develop during childhood and increases in severity with age. The clinical manifestations are highly variable even within the same family. HED2 is suspected after infancy on the basis of physical features in most affected individuals.
Sequence analysis can be used when none of the four known pathogenic variants is identified. Special hair care products to help manage dry and sparse hair; wigs; artificial nails; emollients to relieve palmoplantar hyperkeratosis. Displazia is inherited in an autosomal dominant manner.
Orphanet: Displasia ectodermica idrotica
Most individuals with HED2 have an affected parent; de novo pathogenic variants have also been reported. Prenatal testing for pregnancies at increased risk is dctodermica if the pathogenic variant in an affected family member is known; however, requests for prenatal testing for conditions such as HED2 are not common.
The diagnosis of hidrotic ectodermal dysplasia 2 HED2, Clouston syndrome should be considered after infancy in individuals with the following:. View in own window.
Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene. Pathogenic variants detected include: See Molecular Genetics for populations with these pathogenic variants. Pathogenic variants included in a panel may vary by laboratory. Sequence analysis detects variants that are benign, likely benign, of uncertain significancelikely pathogenic, or pathogenic.
For issues to consider in interpretation of sequence analysis results, click here. Methods used may include: Hidrotic ectodermal dysplasia 2 HED2, Clouston syndrome is characterized by dystrophy of the nails, alopecia partial or totalhyperpigmentation of the skin especially over the jointspalmoplantar hyperkeratosis, and clubbing of the fingers.
Sweat glands, sebaceous glands, and teeth are normal. HED2 can be characterized by dysplastic nails and sparse scalp hair early in life. During childhood, palmoplantar keratoderma may develop.
In infancy, the scalp hair is wiry, brittle, patchy, and pale. Progressive hair loss may lead to total alopecia, usually by puberty. Hair in other parts of the body may also be affected.
In early childhood, the nails may be milky white. They gradually become dystrophic, thick, short, and distally separated from the nail bed. Nail growth is slow. Ala88Val pathogenic variants can be associated with a clinical picture similar to that of pachyonychia congenita [ van Steensel et al ] see Differential Diagnosis.
In one Chinese family, hidrotic ectodermal dysplasia 2 caused by the p. Gly11Arg pathogenic variant involved only hair and nails [ Chen et al ]. When referring to HED2 Clouston syndromethe nonspecific term ‘hidrotic ectodermal dysplasia’ should not be used, as other forms of ectodermal dysplasia are associated with normal sweating. Jan et al  reported a boy age six years with erythrokeratoderma and some similarities to KID syndrome. Sporadic neoplasms including eccrine syringofibroadenomas occurring as single tumors in the absence of any other findings of this syndrome frequently harbor somatic variants in GJB6 that are not present in the germline ; thus, predisposition to these tumors is not heritable.
Hidrotic ectodermal dysplasia 2 HED2 must be differentiated from the following ectodermal dysplasias that can affect nails and hair. Ability to sweat and oligodontia in these disorders are variable. A novel pathogenic missense variant in GJB2 associated with thin hair, deafness, and nail dystrophy resembles HED2 with deafness [ van Steensel et al ]. Rafiq et al  studied an autosomal recessive form of ectodermal dysplasia ED OMIM in 13 individuals over six generations from a consanguineous Pakistani family.
The clinical features include severely dystrophic nails and thin scalp hair, fine eyebrows and eyelashes, and thin body hair. Linkage analysis mapped the ED-related gene on chromosome 10q Isolated nail dystrophy can also be a finding of Darier disease OMIM and acquired disorders such as lichen planus and psoriasis. Associated symptoms and history should allow easy differentiation.
See Ectodermal dysplasia select examples: To establish the extent of disease and needs in an individual diagnosed with hidrotic ectodermal dysplasia 2 HED2, Clouston syndromea thorough examination of the nails, hair, and skin is recommended. Clinical genetics consultation may also be considered.
No special pharmaceutical agent is available to improve hair growth. Alopecia was found to respond to treatment with a combination of topical minoxidil and tretinoin in an individual with probable congenital hidrotic ectodermal dysplasia [ Melkote et al ]. The authors also noted that the efficacy and safety of long-term treatment need to be explored further. Skin emollients may help relieve palmoplantar hyperkeratosis. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
There may not be clinical trials for this disorder. Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members.
This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. Hidrotic ectodermal dysplasia 2 HED2, Clouston syndrome is inherited in an autosomal dominant manner. Offspring of a proband. Other family members of a proband. The risk to other family members depends on the status of the proband’s parents: Considerations in families with an apparent de novo pathogenic variant.
When neither parent of a proband with an autosomal dominant condition has the pathogenic variant or clinical evidence of the disorder, the pathogenic variant is likely de novo. However, possible non-medical explanations including alternate paternity or maternity e.
DNA banking is the storage of DNA typically extracted from white blood cells for possible future ccongenita. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.
Once the GJB6 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for HED2 are possible. Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis.
While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate. GeneReviews is not responsible for the conggenita provided by other organizations. For information on selection criteria, click here. Data are compiled from the following standard ectoderica GJB6 has one exonwhich is not interrupted by introns. For a detailed summary of gene and protein information, see Table AGene.
Note on variant classification: Variants listed in the table have been provided by the author. GeneReviews staff have not independently displasiia the classification of variants. See Quick Reference for an explanation of nomenclature.
Lamartine et al Smith et al Zhang et al Baris et al . Found in a simplex case i. Affects the first extracellular loop of the connexin 30 molecule; found among individuals of Ashkenazi Jewish ancestry.
A de novo pathogenic variant has been reported [ Smith et al ]. Gap junction beta-6 protein comprises amino acids and four transmembrane domains, two extracellular domains, and three cytoplasmic domains including the amino- and carboxy-terminal regions. Gap junction beta-6 protein, with five other similar subunits, forms a gap junction channel, the connexon, which mediates the direct diffusion of ions and metabolites between the cytoplasm of adjacent cells.
GJB6 is expressed most abundantly in brain and skin. The presence of the mutated protein may lead to a defect in trafficking of other gap junction protein subunits, since their oligomerization is complete upon entry into the Golgi apparatus [ Evans et alvan Steensel ]. Several pathogenic variants in genes encoding related gap junction proteins result in mistrafficking of the protein [ Common et al ].
In that case, the pathogenic variants of GJB6 should interfere with its incorporation into the gap junction. So far, this hypothesis has not been experimentally validated [ van Steensel ]. However, evidence was provided that GJB6 could be a transcriptional target gene of p63, elucidating further the process of the development of the skin and the morphogenesis of its appendages [ Fujimoto et al ].
Certain hidrotic ectodermal dysplasia 2 variants may be associated with eccrine syringofibroadenomas, ectpdermica rare benign neoploasm derived from acrosyringium cells of the eccrine sudoriferous glands [ Andrade et al ]. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that i credit for source http: No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports ectodermlca clinic notes are a permitted use.
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