scholarly journals Natural history of X-linked hypohidrotic ectodermal dysplasia: a 5-year follow-up study

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Sigrun Wohlfart ◽  
Ralph Meiller ◽  
Johanna Hammersen ◽  
Jung Park ◽  
Johannes Menzel-Severing ◽  
...  
Keyword(s):  
Natural History ◽  
Ectodermal Dysplasia ◽  
Prenatal Development ◽  
Psychomotor Development ◽  
Deciduous Teeth ◽  
Female Group ◽  
Hypohidrotic Ectodermal Dysplasia ◽  
Pathogenic Variants ◽  
Tooth Germs ◽  
Male Subjects

Abstract Background X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by pathogenic variants of the gene EDA disrupting the prenatal development of ectodermal derivatives. Cardinal symptoms are hypotrichosis, lack of teeth, and hypo- or anhidrosis, but the disease may also evoke other clinical problems. This study aimed at investigating the clinical course of XLHED in early childhood as the basis for an evaluation of the efficacy of potential treatments. Methods 25 children (19 boys and 6 girls between 11 and 35 months of age) with genetically confirmed XLHED were enrolled in a long-term natural history study. Clinical data were collected both retrospectively using parent questionnaires and medical records (pregnancy, birth, infancy) and prospectively until the age of 60 months. General development, dentition, sweating ability, ocular, respiratory, and skin involvement were assessed by standardized clinical examination and yearly quantitative surveys. Results All male subjects suffered from persistent anhidrosis and heat intolerance, although a few sweat ducts were detected in some patients. Sweating ability of girls with XLHED ranged from strongly reduced to almost normal. In the male subjects, 1–12 deciduous teeth erupted and 0–8 tooth germs of the permanent dentition became detectable. Tooth numbers were higher but variable in the female group. Most affected boys had no more than three if any Meibomian glands per eyelid, most girls had fewer than 10. Many male subjects developed additional, sometimes severe health issues, such as obstructive airway conditions, chronic eczema, or dry eye disease. Adverse events included various XLHED-related infections, unexplained fever, allergic reactions, and retardation of psychomotor development. Conclusions This first comprehensive study of the course of XLHED confirmed the early involvement of multiple organs, pointing to the need of early therapeutic intervention.

scholarly journals High penetrance of EDA pathogenic variants in Mexican female carriers with hypohidrotic ectodermal dysplasia

2020 ◽  
Vol 38 (3) ◽  
pp. 172
Author(s):  
Nancy Monroy-Jaramillo ◽  
Constanza Garcia-Delgado ◽  
MiguelAngel Noriega-Juárez ◽  
Alicia Cervantes ◽  
JoséD Abad-Flores ◽  
...  
Keyword(s):  
Ectodermal Dysplasia ◽  
Hypohidrotic Ectodermal Dysplasia ◽  
Pathogenic Variants ◽  
High Penetrance ◽  
Female Carriers

scholarly journals EDA, EDAR, EDARADD and WNT10A allelic variants in patients with ectodermal derivative impairment in the Spanish population

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
María Carmen Martínez-Romero ◽  
◽  
María Juliana Ballesta-Martínez ◽  
Vanesa López-González ◽  
María José Sánchez-Soler ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Ectodermal Dysplasia ◽  
Molecular Study ◽  
Spanish Population ◽  
Hypohidrotic Ectodermal Dysplasia ◽  
Allelic Variants ◽  
Pathogenic Variants ◽  
Ectodermal Dysplasias ◽  
Next Generation Sequencing Ngs ◽  
Gene 4

Abstract Background Ectodermal dysplasias (ED) are a group of genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives. An attenuated phenotype is considered a non-syndromic trait when the patient is affected by only one impaired ectodermal structure, such as in non-syndromic tooth agenesis (NSTA) disorder. Hypohidrotic ectodermal dysplasia (HED) is the most highly represented ED. X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common subtype, with an incidence of 1/50,000–100,000 males, and is associated with the EDA gene (Xq12-q13.1); the dominant and recessive subtypes involve the EDAR (2q13) and EDARADD (1q42.3) genes, respectively. The WNT10A gene (2q35) is associated more frequently with NSTA. Our goal was to determine the mutational spectrum in a cohort of 72 Spanish patients affected by one or more ectodermal derivative impairments referred to as HED (63/72) or NSTA (9 /72) to establish the prevalence of the allelic variants of the four most frequently associated genes. Sanger sequencing of the EDA, EDAR, EDARADD and WNT10A genes and multiplex ligation-dependent probe amplification (MLPA) were performed. Results A total of 61 children and 11 adults, comprising 50 males and 22 females, were included. The average ages were 5.4 and 40.2 years for children and adults, respectively. A molecular basis was identified in 51/72 patients, including 47/63 HED patients, for whom EDA was the most frequently involved gene, and 4/9 NSTA patients, most of whom had variants of WNT10A. Among all the patients, 37/51 had variants of EDA, 8/51 had variants of the WNT10A gene, 4/51 had variants of EDAR and 5/51 had variants of EDARADD. In 42/51 of cases, the variants were inherited according to an X-linked pattern (27/42), with the remaining showing an autosomal dominant (10/42) or autosomal recessive (5/42) pattern. Among the NSTA patients, 3/9 carried pathogenic variants of WNT10A and 1/9 carried EDA variants. A total of 60 variants were detected in 51 patients, 46 of which were different, and out of these 46 variants, 12 were novel. Conclusions This is the only molecular study conducted to date in the Spanish population affected by ED. The EDA, EDAR, EDARADD and WNT10A genes constitute the molecular basis in 70.8% of patients with a 74.6% yield in HED and 44.4% in NSTA. Twelve novel variants were identified. The WNT10A gene has been confirmed as the second molecular candidate that has been identified and accounts for one-half of non-EDA patients and one-third of NSTA patients. Further studies using next generation sequencing (NGS) will help to identify other contributory genes in the remaining uncharacterized Spanish patients.

Skin

2019 ◽  
pp. 257-260
Author(s):  
Robin D. Clark ◽  
Cynthia J. Curry
Keyword(s):  
Clinical Case ◽  
Ectodermal Dysplasia ◽  
The Other ◽  
Sweat Glands ◽  
Hypohidrotic Ectodermal Dysplasia ◽  
Case Presentation ◽  
Pathogenic Variants ◽  
Ectodermal Dysplasias ◽  
Dental Management

This chapter reviews the various types of congenital ectodermal dysplasias (ED). These present variably with involvement of skin, teeth, sweat glands, hair, and nails. In the newborn period ED can resemble ichthyosis with erythema and scaling. X-lLinked hypohidrotic ectodermal dysplasia is the most common form and may affect girls as well as boys. This can cause infant overheating with serious sequelae. Long term dental management is needed for this disorder as well as for most of the other ED’s. Several ED syndromes involve immunodeficiency. Several allelic rare multiple anomaly ED syndromes are caused by pathogenic variants in TP63. The clinical case presentation features an infant with autosomal recessive hypohidrotic ectodermal dysplasia.

scholarly journals No evidence for preferential X-chromosome inactivation as the main cause of divergent phenotypes in sisters with X-linked hypohidrotic ectodermal dysplasia

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Laura Körber ◽  
Holm Schneider ◽  
Nicole Fleischer ◽  
Sigrun Maier-Wohlfart
Keyword(s):  
X Chromosome ◽  
Peripheral Blood ◽  
Ectodermal Dysplasia ◽  
Phenotypic Variability ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Peripheral Blood Leukocytes ◽  
Hypohidrotic Ectodermal Dysplasia ◽  
Blood Leukocytes ◽  
Pathogenic Variants

Abstract Background X-linked hypohidrotic ectodermal dysplasia (XLHED), a rare genetic disorder, affects the normal development of ectodermal derivatives, such as hair, skin, teeth, and sweat glands. It is caused by pathogenic variants of the gene EDA and defined by a triad of hypotrichosis, hypo- or anodontia, and hypo- or anhidrosis which may lead to life-threatening hyperthermia. Although female carriers are less severely affected than male patients, they display symptoms, too, with high phenotypic variability. This study aimed to elucidate whether phenotypic differences in female XLHED patients with identical EDA genotypes might be explained by deviating X-chromosome inactivation (XI) patterns. Methods Six families, each consisting of two sisters with the same EDA variant and their parents (with either mother or father being carrier of the variant), participated in this study. XLHED-related data like sweating ability, dental status, facial dysmorphism, and skin issues were assessed. We determined the women`s individual XI patterns in peripheral blood leukocytes by the human androgen receptor assay and collated the results with phenotypic features. Results The surprisingly large inter- and intrafamilial variability of symptoms in affected females was not explicable by the pathogenic variants. Our cohort showed no higher rate of nonrandom XI in peripheral blood leukocytes than the general female population. Furthermore, skewed XI patterns in favour of the mutated alleles were not associated with more severe phenotypes. Conclusions We found no evidence for preferential XI in female XLHED patients and no distinct correlation between XLHED-related phenotypic features and XI patterns. Phenotypic variability seems to be evoked by other genetic or epigenetic factors.

A rare cause of fever of unknown origin: hypohidrotic ectodermal dysplasia with a splice site mutation

2018 ◽  
Vol 70 (5) ◽  
Author(s):  
Melahat M. Oguz ◽  
Meltem Akcaboy ◽  
Asuman Gurkan ◽  
Esma Altinel Acoglu ◽  
Pelin Zorlu ◽  
...  
Keyword(s):  
Splice Site ◽  
Fever Of Unknown Origin ◽  
Ectodermal Dysplasia ◽  
Splice Site Mutation ◽  
Unknown Origin ◽  
Hypohidrotic Ectodermal Dysplasia ◽  
Site Mutation

scholarly journals One Mutation of the ED1 Gene in a Chinese Han Family with X-Linked Hypohidrotic Ectodermal Dysplasia

2014 ◽  
Vol 26 (1) ◽  
pp. 111 ◽  
Author(s):  
Jing Wang ◽  
Wei-Wei Ha ◽  
Wen Wang ◽  
Hua-Yang Tang ◽  
Xian-Fa Tang ◽  
...  
Keyword(s):  
Ectodermal Dysplasia ◽  
Hypohidrotic Ectodermal Dysplasia ◽  
Chinese Han

scholarly journals A novel de novo DDX3X missense variant in a female with brachycephaly and intellectual disability: a case report

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Giada Moresco ◽  
Jole Costanza ◽  
Carlo Santaniello ◽  
Ornella Rondinone ◽  
Federico Grilli ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Clinical Presentation ◽  
De Novo ◽  
Clinical Signs ◽  
Missense Variant ◽  
Psychomotor Development ◽  
Helicase Domain ◽  
Protein Activity ◽  
Mrna Metabolism ◽  
Pathogenic Variants

Abstract Background De novo pathogenic variants in the DDX3X gene are reported to account for 1–3% of unexplained intellectual disability (ID) in females, leading to the rare disease known as DDX3X syndrome (MRXSSB, OMIM #300958). Besides ID, these patients manifest a variable clinical presentation, which includes neurological and behavioral defects, and abnormal brain MRIs. Case presentation We report a 10-year-old girl affected by delayed psychomotor development, delayed myelination, and polymicrogyria (PMG). We identified a novel de novo missense mutation in the DDX3X gene (c.625C > G) by whole exome sequencing (WES). The DDX3X gene encodes a DEAD-box ATP-dependent RNA-helicase broadly implicated in gene expression through regulation of mRNA metabolism. The identified mutation is located just upstream the helicase domain and is suggested to impair the protein activity, thus resulting in the altered translation of DDX3X-dependent mRNAs. The proband, presenting with the typical PMG phenotype related to the syndrome, does not show other clinical signs frequently reported in presence of missense DDX3X mutations that are associated with a most severe clinical presentation. In addition, she has brachycephaly, never described in female DDX3X patients, and macroglossia, that has never been associated with the syndrome. Conclusions This case expands the knowledge of DDX3X pathogenic variants and the associated DDX3X syndrome phenotypic spectrum.

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