Paula and Bobby
Parents of Lillie
Ectodermal Dysplasia 1, Hypohidrotic, X-Linked (XHED)
What is Ectodermal Dysplasia 1, Hypohidrotic, X-Linked (XHED)?
Ectodermal Dysplasia is a diverse group of genetic disorders, thought to number over 180 types.
These congenital disorders are characterized by abnormalities in two or more ectodermal structures such as the hair, nails, teeth, or sweat glands; but without any other systemic findings.
Anhidrotic ectodermal dysplasia Christ-siemens-touraine Syndrome Cst Syndrome Ectodermal Dysplasia 1, Hypohidrotic/hair/tooth Type, X-linked; Ectd1 Ectodermal Dysplasia 1; Ed1 Ectodermal Dysplasia, Anhidrotic, X-linked; Eda Ectodermal Dysplasia, Anhidrotic; Eda Ectodermal Dysplasia, Hypohidrotic, 1; Hed1 Ectodermal Dysplasia, Hypohidrotic; Hed Eda1 HED Hyperpigmentation of Eyelids Hypohidrotic ectodermal dysplasia - X-linked form Xlhed
What gene changes cause Ectodermal Dysplasia 1, Hypohidrotic, X-Linked (XHED)?
The disorder is X-linked, and the result of mutations in the EDA gene. These mutations affect the ectoderm, the layer of cells around the outside of the body of the developing fetus from which the hair, skin and nails develop. This triggers the abnormal tissue growth associated with the syndrome.
Syndromes inherited in an X-linked recessive pattern generally only affect males. Males only have one X chromosome, and so one copy of a gene mutation on it causes the syndrome. Females, with two X chromosomes, only one of which will be mutated, are not likely to be affected.
What are the main symptoms of Ectodermal Dysplasia 1, Hypohidrotic, X-Linked (XHED)?
The type of syndromes an individual may have will depend on which type of the disorder they have.
Different types of the disorder trigger different physical symptoms which may vary in degree and severity between individuals.
Possible symptoms include teeth abnormalities, spare and or absent hair, and skin issues.
Possible clinical traits/features:
Abnormal number of teeth, Abnormality of the forehead, Abnormality of the nose, Anhidrosis, Absent nipple, Sparse hair, Everted lower lip vermilion, Ectodermal dysplasia, Dry skin
How does someone get tested for Ectodermal Dysplasia 1, Hypohidrotic, X-Linked (XHED)?
The initial testing for Ectodermal Dysplasia syndrome can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.
Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.
Medical information on Ectodermal Dysplasia 1, Hypohidrotic, X-Linked (XHED)
Also called Christ-Siemens-Touraine syndrome, this is the commonest of the ectodermal dysplasias. Affected males are of normal intelligence but have sparse scalp hair, eyebrows and eyelashes, and no body hair. They do not sweat and often present in infancy with high fevers. Most teeth are missing and those that do appear are of abnormal shape, mostly conical in outline. There is often pigmentation and dryness of skin around the eyes and most males have a prominent forehead, a saddle nose, prominent lips and a hoarse voice. A collodion-like picture can occur (Thomas et al., 2006). Both lacrimation and salivary secretions can be reduced. The patient reported by Ben Simon and Grinbaum (2004), had keratoconus and corneal perforation. Obligate carrier females might have sparse hair, but the best diagnostic signs, not always present, are abnormal dentition (oligodontia and abnormal size and shape) (Ruhin et al., 2001) and an abnormal pattern of sweat distribution. Note the unusual family reported by Sandhu et al., (2007) with palmoplantar hyperkeratosis. Occasional fully affected females with balanced translocations affecting EDA locus have been reported (Zankl et al., 2001). A severely affected female (other females in the family were mild or unaffected - not stated) reported by Kim et al., (2011), in a Korean family had an additional G198R mutation, that was probably the cause of the severity. Carrier females can have amastia (Ali et al., 2014)
Milia is an unusual finding (Mehta et al., 2014)
Note that in hot countries, the hyperthermia can have serious consequences - cerebral infarction, elevated liver enzymes, muscle necrosis - Prasun et al., (2012).
A case with a neuroblastoma was reported by Buoni et al., (2007) and one with infantile bilateral glaucoma by Callea et al., (2013)
Note that some of the males might have hypodontia alone (Fan et al., 2008).
The gene has been mapped to Xq12-13 (See Zonana et al., 1992 for review). Zonana et al., (1993) reported a deletion of the probe DXS732 in a family, with the generation of a junction fragment. Zonana et al., (1994) demonstrated the origin of mutation in ten families using linkage studies (although three cases had molecular deletions). There was a 3.5:1 male to female excess of the origin of mutation.
Kere et al., (1996) demonstrated mutations in a gene encoding a predicted transmembrane protein expressed in keratinocytes, hair follicles and sweat glands. Ferguson et al., (1998) could only find mutations in about 7% of affected males, however. They concluded that the remainder of the patients were likely to have mutations in unidentified exons of the gene. Ezer et al., (1997) demonstrated that the protein associates with the cell membrane and induces rounding in epithelial cell lines. Bayes et al., (1998) showed that the gene (EDA1) undergoes alternative splicing. The longest transcript, EDA1--A encodes at 391 amino acid transmembrane protein with a short collagenous domain. SSCP analysis of the nine exons of the EDA1-A form identified mutations in twelve out of fifteen patients. Monreal et al., (1998) identified a new splice form of the EDA1 gene incorporating seven new exons. Mutations were found in 95% of patients. Further mutations were reported by Vincent et al., (2001), Visinoni et al., (2003) and Sekiguchi et al., (2005).
Munoz et al., (1997) provided good evidence that an autosomal recessive form does occur with features identical to the X-linked recessive forms in males. Bhat et al., (2009) reported a female with the full-blown picture born to 2nd cousin parents. Father to son transmission was reported by Ferrier et al., (2009). Further analysis showed paternal UPD (uniparental disomy). There is a suggestion (Cluzeau et al., (2012) that the EDAR370A might alter severity.
* This information is courtesy of the L M D.
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