X-linked hypohidrotic ectodermal dysplasia (XLHED, Christ-Siemens-Touraine syndrome) is an X-linked disorder caused by pathogenic variants in EDA, which encodes the TNF-superfamily ligand ectodysplasin A. Deficient EDA-EDAR-EDARADD signaling reduces canonical NF-kappaB activation, disrupting ectodermal placode formation and the morphogenesis of hair follicles, teeth, eccrine sweat glands, and other secretory glands. Affected males typically have the classic triad of hypohidrosis, sparse hair, and hypodontia, often with conical teeth. Heterozygous females may show variable, usually milder manifestations. Markedly deficient sweating creates a risk of life-threatening hyperthermia, particularly in infancy and early childhood. In a Danish population study, molecularly confirmed XLHED had a point prevalence of 1.6 per 100,000.
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Conditions with similar clinical presentations that must be differentiated from X-linked Hypohidrotic Ectodermal Dysplasia:
name: X-linked Hypohidrotic Ectodermal Dysplasia
creation_date: "2026-04-24T00:00:00Z"
description: >-
X-linked hypohidrotic ectodermal dysplasia (XLHED, Christ-Siemens-Touraine syndrome)
is an X-linked disorder caused by pathogenic variants in EDA, which encodes the
TNF-superfamily ligand ectodysplasin A. Deficient EDA-EDAR-EDARADD signaling reduces
canonical NF-kappaB activation, disrupting ectodermal placode formation and the
morphogenesis of hair follicles, teeth, eccrine sweat glands, and other secretory glands.
Affected males typically have the classic triad of hypohidrosis, sparse hair, and
hypodontia, often with conical teeth. Heterozygous females may show variable, usually
milder manifestations. Markedly deficient sweating creates a risk of life-threatening
hyperthermia, particularly in infancy and early childhood. In a Danish population study,
molecularly confirmed XLHED had a point prevalence of 1.6 per 100,000.
category: Genetic
parents:
- Ectodermal Dysplasia
disease_term:
preferred_term: X-linked hypohidrotic ectodermal dysplasia
term:
id: MONDO:0010585
label: X-linked hypohidrotic ectodermal dysplasia
references:
- reference: PMID:20301291
title: Hypohidrotic Ectodermal Dysplasia.
tags:
- GeneReviews
- reference: PMID:24664614
title: "X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry."
- reference: PMID:23416623
title: "The prevalence of X-linked hypohidrotic ectodermal dysplasia (XLHED) in Denmark, 1995-2010."
- reference: PMID:21357618
title: Sweating ability and genotype in individuals with X-linked hypohidrotic ectodermal dysplasia.
- reference: PMID:39244550
title: Genetic profiling and diagnostic strategies for patients with ectodermal dysplasias in Korea.
- reference: PMID:29694819
title: Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia.
prevalence:
- population: Denmark, January 1, 2011
measure_type: POINT_PREVALENCE
prevalence_class: BAND_1_9_PER_100000
rate_per_100000: 1.6
notes: >-
This estimate is restricted to molecularly confirmed XLHED. The broader
registry-and-algorithm estimate included clinically diagnosed or possible HED
and is not used as an XLHED-specific prevalence rate.
evidence:
- reference: PMID:23416623
reference_title: "The prevalence of X-linked hypohidrotic ectodermal dysplasia (XLHED) in Denmark, 1995-2010."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The prevalence was 21.9 per 100,000 overall and 1.6 per 100,000 when
restricting to molecularly-confirmed XLHED cases.
explanation: >-
Provides the point-prevalence estimate for molecularly confirmed XLHED in
the Danish population.
progression:
- phase: Infancy to childhood recognition
age_range: Infancy through childhood
notes: >-
The ectodermal defects are congenital, but the cardinal triad often becomes
clinically obvious during childhood. Before families learn temperature-control
measures, markedly deficient sweating can cause episodes of hyperthermia.
evidence:
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The cardinal features of classic HED become obvious during childhood. The
scalp hair is thin, lightly pigmented, and slow growing. Sweating, although
present, is greatly deficient, leading to episodes of hyperthermia until the
affected individual or family acquires experience with environmental
modifications to control temperature.
explanation: >-
GeneReviews describes childhood recognition and the early hyperthermia-prone
phase before environmental adaptations are established.
- phase: Lifelong complications
age_range: Childhood through adulthood
notes: >-
Dental and appendage abnormalities persist, while respiratory, nasal, skin,
and voice complications can require continuing supportive care across life.
evidence:
- reference: PMID:24664614
reference_title: "X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
the registry dataset confirmed a spectrum of life-long XLHED clinical
complications including recurrent sinus infections (49% males, 52% females),
nasal congestion often foul smelling and interfering with feeding (73% males,
27% females), eczema (66% males, 40% females), wheezing (66% males, 45%
females), and a hoarse, raspy voice (67% males, 23% females).
explanation: >-
Registry data document persistent multisystem complications across the
lifespan and quantify several common manifestations.
inheritance:
- name: X-linked
description: >-
EDA-related HED is inherited in an X-linked manner. Hemizygous males who
inherit the familial pathogenic variant are affected; heterozygous females
may manifest ectodermal-dysplasia features.
inheritance_term:
preferred_term: X-linked inheritance
term:
id: HP:0001417
label: X-linked inheritance
evidence:
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
EDA-related HED is inherited in an X-linked manner.
explanation: >-
GeneReviews directly establishes the inheritance mode of EDA-related HED.
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
If the mother of a proband is heterozygous for an EDA pathogenic variant,
the chance of the mother transmitting it in each pregnancy is 50%. If the
father of the proband has an EDA pathogenic variant, he will transmit it to
all his daughters and none of his sons. Males who inherit the pathogenic
variant will be affected; females who inherit the pathogenic variant will
be heterozygous and may show manifestations of ectodermal dysplasia.
explanation: >-
Defines transmission risks and sex-dependent manifestations for X-linked HED.
- reference: PMID:21357618
reference_title: Sweating ability and genotype in individuals with X-linked hypohidrotic ectodermal dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In all 5 heterozygous females, some sweat was detected, but generally less
than in female controls.
explanation: >-
Objective sweat testing documents manifestations in heterozygous females,
supporting the broader X-linked term rather than an assertion that female
heterozygotes are uniformly unaffected.
pathophysiology:
- name: EDA Ligand Deficiency
description: >-
Pathogenic EDA variants cause complete or partial deficiency of ectodysplasin
A1, removing the extracellular ligand that normally activates EDAR during
ectodermal-appendage development.
role: trigger
biological_scale: MOLECULAR
genes:
- preferred_term: EDA
term:
id: hgnc:3157
label: EDA
evidence:
- reference: PMID:37108325
reference_title: "A Causal Treatment for X-Linked Hypohidrotic Ectodermal Dysplasia: Long-Term Results of Short-Term Perinatal Ectodysplasin A1 Replacement."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
X-linked hypohidrotic ectodermal dysplasia (XLHED), caused by a genetic
deficiency of ectodysplasin A1 (EDA1), is a rare developmental disorder of
ectodermal derivatives such as hair, sweat glands, and teeth.
explanation: >-
Directly identifies EDA1 deficiency as the initiating molecular lesion in XLHED.
downstream:
- target: EDA-EDAR-EDARADD Canonical NF-kappaB Signaling Failure
causal_link_type: DIRECT
evidence:
- reference: PMID:24070496
reference_title: "The ectodysplasin pathway: from diseases to adaptations."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
It comprises three main gene products: EDA, a ligand that belongs to the tumor
necrosis factor (TNF)-α family, EDAR, a receptor related to the TNFα receptors,
and EDARADD, a specific adaptor. This core pathway relies on downstream NF-κB
pathway activation to regulate target genes.
explanation: >-
Places EDA directly upstream of EDAR, EDARADD, and NF-kappaB activation.
- name: EDA-EDAR-EDARADD Canonical NF-kappaB Signaling Failure
conforms_to: "eda_edar_nfkb_ectodermal_appendage#EDA-EDAR-EDARADD Canonical NF-kappaB Signaling Failure"
description: >-
EDA ligand deficiency prevents effective EDAR activation and EDARADD-dependent
signaling, reducing canonical NF-kappaB transcriptional activity in developing
surface ectoderm. This also disrupts downstream Wnt, SHH, FGF, and TGF-beta
pathway effectors involved in epithelial-mesenchymal interactions.
role: central_effector
biological_scale: MOLECULAR
cell_types:
- preferred_term: surface ectodermal cell
term:
id: CL:0000114
label: surface ectodermal cell
- preferred_term: keratinocyte
term:
id: CL:0000312
label: keratinocyte
biological_processes:
- preferred_term: canonical NF-kappaB signal transduction
term:
id: GO:0007249
label: canonical NF-kappaB signal transduction
modifier: DECREASED
evidence:
- reference: PMID:24070496
reference_title: "The ectodysplasin pathway: from diseases to adaptations."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
It comprises three main gene products: EDA, a ligand that belongs to the tumor
necrosis factor (TNF)-α family, EDAR, a receptor related to the TNFα receptors,
and EDARADD, a specific adaptor. This core pathway relies on downstream NF-κB
pathway activation to regulate target genes.
explanation: >-
Defines the EDA-EDAR-EDARADD cascade and its dependence on NF-kappaB activation.
- reference: PMID:24508088
reference_title: "Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
The EDA-EDAR system is an important effector of canonical Wnt signalling in
developing skin appendages. It functions by stimulating NF-κB-mediated
transcription of effectors or inhibitors of the Wnt, Sonic hedgehog (SHH),
fibroblast growth factor (FGF) and transforming growth factor beta (TGFβ)
pathways that regulate interactions within or between epithelial and mesenchymal
cells and tissues.
explanation: >-
Defines the downstream transcriptional pathways perturbed by reduced EDA-EDAR
signaling, based primarily on model-organism studies.
downstream:
- target: Failed Ectodermal Placode Formation
causal_link_type: DIRECT
- name: Failed Ectodermal Placode Formation
conforms_to: "eda_edar_nfkb_ectodermal_appendage#Failed Ectodermal Placode Formation"
description: >-
Reduced EDA-EDAR-NF-kappaB activity impairs induction of ectodermal placodes,
the focal epithelial thickenings that initiate hair follicles, teeth, and sweat
glands. The resulting epithelial-mesenchymal developmental program is therefore
not properly specified.
role: central_effector
biological_scale: TISSUE
cell_types:
- preferred_term: surface ectodermal cell
term:
id: CL:0000114
label: surface ectodermal cell
biological_processes:
- preferred_term: ectodermal placode formation
term:
id: GO:0060788
label: ectodermal placode formation
modifier: DECREASED
evidence:
- reference: PMID:24508088
reference_title: "Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
The TNF family ligand ectodysplasin A (EDA) regulates the induction,
morphogenesis and/or maintenance of skin-derived structures such as teeth, hair,
sweat glands and several other glands.
explanation: >-
Supports EDA-dependent induction and morphogenesis of the appendage primordia.
downstream:
- target: Ectodermal Appendage Morphogenesis Failure
causal_link_type: DIRECT
- name: Ectodermal Appendage Morphogenesis Failure
conforms_to: "eda_edar_nfkb_ectodermal_appendage#Ectodermal Appendage Morphogenesis Failure"
description: >-
Failed placode-dependent morphogenesis produces the shared developmental
abnormalities of eccrine sweat glands, hair follicles, and teeth that underlie
the classic XLHED triad.
role: consequence
biological_scale: TISSUE
biological_processes:
- preferred_term: sweat gland development
term:
id: GO:0060792
label: sweat gland development
modifier: DECREASED
- preferred_term: hair follicle development
term:
id: GO:0001942
label: hair follicle development
modifier: DECREASED
- preferred_term: odontogenesis of dentin-containing tooth
term:
id: GO:0042475
label: odontogenesis of dentin-containing tooth
modifier: DECREASED
evidence:
- reference: PMID:22421994
reference_title: "Orofacial features of hypohidrotic ectodermal dysplasia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Hypohidrotic ectodermal dysplasia (HED) is a type of genodermatosis
characterized by the abnormal development of sweat glands, teeth, and hair.
explanation: >-
Establishes the conserved appendage-development triad in HED.
downstream:
- target: Eccrine Sweat Gland Aplasia/Hypoplasia
causal_link_type: DIRECT
- target: Hair Follicle Developmental Failure
causal_link_type: DIRECT
- target: Tooth Developmental Defects
causal_link_type: DIRECT
- target: Secretory Gland Developmental Dysfunction
causal_link_type: DIRECT
- name: Eccrine Sweat Gland Aplasia/Hypoplasia
description: >-
Deficient EDA signaling during embryogenesis impairs eccrine sweat-gland
development. Affected males may have no detectable sweat pores or only a few
pores, with absent or markedly reduced inducible sweating.
biological_scale: TISSUE
cell_types:
- preferred_term: eccrine cell
term:
id: CL:0000434
label: eccrine cell
biological_processes:
- preferred_term: sweat gland development
term:
id: GO:0060792
label: sweat gland development
modifier: DECREASED
evidence:
- reference: PMID:29694819
reference_title: "Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic
ectodermal dysplasia (XLHED), in which the development of sweat glands is
irreversibly impaired, an condition that can lead to life-threatening hyperthermia.
explanation: >-
Establishes that EDA deficiency irreversibly impairs sweat gland development,
causing life-threatening hyperthermia.
- reference: PMID:21357618
reference_title: Sweating ability and genotype in individuals with X-linked hypohidrotic ectodermal dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Among 31 XLHED males, 14 had neither detectable sweat pores nor inducible
sweating, 10 showed a few sweat pores but absent sweating, and 7 produced
reduced sweat volumes (1-11 μl) as compared with controls (38-93 μl).
explanation: >-
Quantifies absent sweat pores, absent inducible sweating, and residual sweat
production in genotyped males with XLHED.
downstream:
- target: Hypohidrosis
causal_link_type: DIRECT
- target: Hyperthermia Risk
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- Loss of evaporative cooling because sweating is absent or markedly reduced.
- name: Hair Follicle Developmental Failure
description: >-
Deficient EDA/EDAR signaling impairs hair follicle initiation and development,
resulting in sparse, thin, lightly pigmented, and slowly growing scalp and body hair.
biological_scale: TISSUE
biological_processes:
- preferred_term: hair follicle development
term:
id: GO:0001942
label: hair follicle development
modifier: DECREASED
evidence:
- reference: PMID:24508088
reference_title: "Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
The TNF family ligand ectodysplasin A (EDA) regulates the induction,
morphogenesis and/or maintenance of skin-derived structures such as teeth,
hair, sweat glands and several other glands.
explanation: >-
Confirms EDA role in development of hair and other skin-derived structures,
established primarily in animal models.
downstream:
- target: Sparse Hair
causal_link_type: DIRECT
- name: Tooth Developmental Defects
description: >-
Deficient EDA signaling disrupts tooth morphogenesis, causing congenital absence
of teeth and abnormal shape of erupted teeth.
biological_scale: TISSUE
biological_processes:
- preferred_term: odontogenesis of dentin-containing tooth
term:
id: GO:0042475
label: odontogenesis of dentin-containing tooth
modifier: DECREASED
evidence:
- reference: PMID:22421994
reference_title: "Orofacial features of hypohidrotic ectodermal dysplasia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Hypohidrotic ectodermal dysplasia (HED) is a type of genodermatosis
characterized by the abnormal development of sweat glands, teeth, and hair.
explanation: >-
Confirms dental abnormalities as a key feature of HED.
downstream:
- target: Hypodontia
causal_link_type: DIRECT
- target: Conical Teeth
causal_link_type: DIRECT
- name: Secretory Gland Developmental Dysfunction
description: >-
EDA regulates several skin-derived glands in addition to eccrine sweat glands.
XLHED is associated with dry eyes, crusted secretions, nasal congestion, and
airway infections, but the relative contributions of abnormal gland development,
altered secretions, and other airway factors are not fully resolved.
biological_scale: TISSUE
biological_processes:
- preferred_term: gland development
term:
id: GO:0048732
label: gland development
modifier: DECREASED
downstream:
- target: Nasal Congestion
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
- target: Wheezing
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
- target: Hoarse Voice
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
- target: Recurrent Respiratory Infections
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
- target: Dry Eyes
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:24508088
reference_title: "Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
The TNF family ligand ectodysplasin A (EDA) regulates the induction,
morphogenesis and/or maintenance of skin-derived structures such as teeth, hair,
sweat glands and several other glands.
explanation: >-
Supports an EDA-dependent developmental role in glands beyond eccrine sweat glands.
- reference: PMID:24664614
reference_title: "X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
the registry dataset confirmed a spectrum of life-long XLHED clinical
complications including recurrent sinus infections (49% males, 52% females),
nasal congestion often foul smelling and interfering with feeding (73% males,
27% females)
explanation: >-
Registry data document respiratory and nasal complications without proving a
single structural mechanism.
- reference: PMID:24508088
reference_title: "Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This syndrome is characterized by the absence or malformation of several
skin-derived appendages resulting in hypotrychosis, hypodontia, heat-intolerance,
dry skin and dry eyes, susceptibility to airways infections and crusting of
various secretions.
explanation: >-
Describes the dry-eye, secretion-crusting, and airway-infection phenotype
associated with EDA-pathway deficiency.
- name: Hyperthermia Risk
description: >-
The absence of functional eccrine sweat glands renders affected individuals unable to
dissipate heat through evaporative cooling. This creates a risk of life-threatening
hyperthermia, especially during febrile illness, exercise, or hot weather. Unexplained
fevers in infancy may be the presenting sign.
biological_scale: ORGANISM
evidence:
- reference: PMID:24928340
reference_title: "Ectodysplasin research--where to next?"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In humans, HED is a life-threatening condition in particular in infants due to
absent or severely reduced sweating leading to hyperthermia.
explanation: >-
Confirms the life-threatening nature of hyperthermia in HED, especially in infants.
- reference: PMID:24678015
reference_title: "Future developments in XLHED treatment approaches."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In the first years of life, XLHED-affected patients are at risk for
life-threatening hyperthermia and pulmonary infection.
explanation: >-
Confirms hyperthermia risk is greatest in early childhood.
downstream:
- target: Heat Intolerance
causal_link_type: DIRECT
phenotypes:
- name: Hypohidrosis
category: Classic
description: >-
Reduced or absent sweating due to aplasia or severe hypoplasia of eccrine sweat glands.
This is the most clinically significant feature due to associated hyperthermia risk.
Reported in 89% of XLHED registrants in the EDIR international registry.
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Hypohidrosis
term:
id: HP:0000966
label: Hypohidrosis
evidence:
- reference: PMID:24664614
reference_title: "X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
XLHED is diagnosed by the triad of decreased sweating, reduced hair, and
hypodontia (present in 89%, 74%, and 74% of XLHED respondents).
explanation: >-
International registry data showing decreased sweating in 89% of XLHED respondents.
- reference: PMID:19681132
reference_title: "Molecular aspects of hypohidrotic ectodermal dysplasia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Hypohidrotic (anhidrotic) ectodermal dysplasia (HED) is a congenital syndrome
characterized by sparse hair, oligodontia, and reduced sweating.
explanation: >-
Identifies reduced sweating as one of the three cardinal features of HED.
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Hypohidrotic ectodermal dysplasia (HED) is characterized by hypotrichosis
(sparseness of scalp and body hair), hypohidrosis (reduced ability to sweat),
and hypodontia (congenital absence of teeth).
explanation: >-
The GeneReviews Clinical Characteristics summary identifies hypohidrosis as
one of the three cardinal manifestations of HED.
- name: Sparse Hair
category: Classic
description: >-
Thin, sparse, light-colored scalp hair with reduced hair follicle density. Body hair
is similarly sparse or absent. Reported in 74% of XLHED registrants.
frequency: FREQUENT
phenotype_term:
preferred_term: Sparse hair
term:
id: HP:0008070
label: Sparse hair
evidence:
- reference: PMID:24664614
reference_title: "X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
XLHED is diagnosed by the triad of decreased sweating, reduced hair, and
hypodontia (present in 89%, 74%, and 74% of XLHED respondents).
explanation: >-
Registry data showing reduced hair in 74% of respondents.
- reference: PMID:19681132
reference_title: "Molecular aspects of hypohidrotic ectodermal dysplasia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Hypohidrotic (anhidrotic) ectodermal dysplasia (HED) is a congenital syndrome
characterized by sparse hair, oligodontia, and reduced sweating.
explanation: >-
Sparse hair is identified as one of the three cardinal features of HED.
- name: Hypodontia
category: Classic
description: >-
Congenital absence of one or more teeth. Erupted teeth may be few, abnormally
shaped, and delayed. Hypodontia was reported in 74% of XLHED registry respondents.
frequency: FREQUENT
phenotype_term:
preferred_term: Hypodontia
term:
id: HP:0000668
label: Hypodontia
evidence:
- reference: PMID:24664614
reference_title: "X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
XLHED is diagnosed by the triad of decreased sweating, reduced hair, and
hypodontia (present in 89%, 74%, and 74% of XLHED respondents).
explanation: >-
Registry data showing hypodontia in 74% of respondents.
- name: Conical Teeth
category: Classic
description: >-
Remaining teeth may have a characteristic conical morphology.
phenotype_term:
preferred_term: Conical tooth
term:
id: HP:0000698
label: Conical tooth
evidence:
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Early dental treatment; bonding of conical teeth; orthodontics as necessary;
explanation: >-
GeneReviews explicitly addresses conical teeth in the management of HED,
corroborating this dental morphology without relying on full-text-only evidence.
- name: Heat Intolerance
category: Classic
description: >-
Inability to tolerate warm environments due to defective thermoregulation
from absent eccrine glands. Can lead to life-threatening hyperthermia.
phenotype_term:
preferred_term: Heat intolerance
term:
id: HP:0002046
label: Heat intolerance
evidence:
- reference: PMID:24508088
reference_title: "Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This syndrome is characterized by the absence or malformation of several
skin-derived appendages resulting in hypotrychosis, hypodontia,
heat-intolerance, dry skin and dry eyes
explanation: >-
Heat intolerance listed as a defining feature of HED.
- name: Nasal Congestion
category: Respiratory
description: >-
Chronic nasal congestion, often foul smelling and interfering with feeding in
infancy, was reported in 73% of males and 27% of females in the EDIR registry.
phenotype_term:
preferred_term: Nasal congestion
term:
id: HP:0001742
label: Nasal congestion
evidence:
- reference: PMID:24664614
reference_title: "X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
nasal congestion often foul smelling and interfering with feeding (73% males,
27% females)
explanation: >-
Registry data quantifying nasal congestion frequency in XLHED.
- name: Wheezing
category: Respiratory
description: >-
Recurrent wheezing was reported in 66% of males and 45% of females in the
EDIR registry; both estimates fall in the frequent range.
frequency: FREQUENT
phenotype_term:
preferred_term: Wheezing
term:
id: HP:0030828
label: Wheezing
evidence:
- reference: PMID:24664614
reference_title: "X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
wheezing (66% males, 45% females)
explanation: >-
Registry data quantifying wheezing frequency in XLHED.
- name: Hoarse Voice
category: Respiratory
description: >-
A hoarse or raspy voice was reported in 67% of males and 23% of females in
the EDIR registry, so a single sex-agnostic frequency band is not assigned.
phenotype_term:
preferred_term: Hoarse voice
term:
id: HP:0001609
label: Hoarse voice
evidence:
- reference: PMID:24664614
reference_title: "X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
a hoarse, raspy voice (67% males, 23% females)
explanation: >-
Registry data quantifying hoarse voice frequency in XLHED.
- name: Dry Skin
category: Dermatologic
description: >-
Xerosis is a recognized HED manifestation.
phenotype_term:
preferred_term: Dry skin
term:
id: HP:0000958
label: Dry skin
evidence:
- reference: PMID:24508088
reference_title: "Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This syndrome is characterized by the absence or malformation of several
skin-derived appendages resulting in hypotrychosis, hypodontia,
heat-intolerance, dry skin and dry eyes
explanation: >-
Dry skin identified as a characteristic feature of HED.
- name: Recurrent Respiratory Infections
category: Respiratory
description: >-
Recurrent sinus infections were reported in 49% of males and 52% of females
in the EDIR registry. Pulmonary infection is an important risk in early life,
although the mechanism is likely multifactorial.
frequency: FREQUENT
phenotype_term:
preferred_term: Recurrent respiratory infections
term:
id: HP:0002205
label: Recurrent respiratory infections
evidence:
- reference: PMID:24664614
reference_title: "X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
the registry dataset confirmed a spectrum of life-long XLHED clinical
complications including recurrent sinus infections (49% males, 52% females),
nasal congestion often foul smelling and interfering with feeding (73% males,
27% females)
explanation: >-
International registry quantifying respiratory complications in XLHED.
- reference: PMID:24678015
reference_title: "Future developments in XLHED treatment approaches."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In the first years of life, XLHED-affected patients are at risk for
life-threatening hyperthermia and pulmonary infection. Survival into childhood
and beyond is associated with severe dental abnormalities as well as chronic
growth, respiratory, skin, eye, and psychosocial disorders.
explanation: >-
Pulmonary infection risk and chronic respiratory disorders are recognized
features of XLHED.
- name: Eczematoid Dermatitis
category: Dermatologic
description: >-
Eczema or atopic dermatitis can occur and was reported in 66% of males and
40% of females in the international XLHED registry.
frequency: FREQUENT
phenotype_term:
preferred_term: Eczematoid dermatitis
term:
id: HP:0000964
label: Eczematoid dermatitis
evidence:
- reference: PMID:24664614
reference_title: "X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
eczema (66% males, 40% females)
explanation: >-
Registry data quantifying eczema frequency in XLHED.
- name: Dry Eyes
category: Ophthalmologic
description: >-
Dry-eye symptoms are a recognized manifestation of EDA-pathway HED.
phenotype_term:
preferred_term: Keratoconjunctivitis sicca
term:
id: HP:0001097
label: Keratoconjunctivitis sicca
evidence:
- reference: PMID:24508088
reference_title: "Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
hypotrychosis, hypodontia, heat-intolerance, dry skin and dry eyes,
susceptibility to airways infections and crusting of various secretions.
explanation: >-
Dry eyes listed as a recognized feature of HED.
genetic:
- name: EDA Pathogenic Variants
gene_term:
preferred_term: EDA
term:
id: hgnc:3157
label: EDA
association: Causative
relationship_type: CAUSATIVE
inheritance:
- name: X-linked
inheritance_term:
preferred_term: X-linked inheritance
term:
id: HP:0001417
label: X-linked inheritance
notes: >-
Identification of a hemizygous pathogenic EDA variant confirms XLHED in an
affected male. Heterozygous females can have manifestations. EDA alleles differ
functionally: some genotypes are consistently associated with anhidrosis, whereas
others retain enough EDA activity to permit measurable sweating. The entry does
not assign variant-class frequencies because broad HED cohorts include genetically
distinct EDAR- and EDARADD-related disease.
variants:
- name: EDA alleles with absent versus residual activity
description: >-
Genotype-phenotype mapping in molecularly confirmed XLHED distinguishes EDA
mutations consistently associated with anhidrosis from mutations that allow
residual EDA-product activity and reduced, but detectable, sweating.
evidence:
- reference: PMID:29855039
reference_title: "Hypohidrotic ectodermal dysplasia: clinical and molecular review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This XL-HED phenotype is associated with mutations in the gene encoding the
transmembrane protein ectodysplasin-1 (EDA1), a member of the TNFα-related
signaling pathway. The proteins from this pathway are involved in signal
transduction from ectoderm to mesenchyme leading to the development of
ectoderm-derived structures in the fetus such as hair, teeth, skin, nails, and
eccrine sweat glands.
explanation: >-
Identifies EDA1 as the causative gene encoding a TNF-family protein essential
for ectodermal appendage development.
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Identification of a hemizygous EDA pathogenic variant in an affected male or
biallelic EDAR, EDARADD, or WNT10A pathogenic variants in an affected male or
female confirms the diagnosis.
explanation: >-
GeneReviews distinguishes EDA-confirmed XLHED from phenotypically overlapping
HED caused by other genes.
- reference: PMID:21357618
reference_title: Sweating ability and genotype in individuals with X-linked hypohidrotic ectodermal dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Among 26 different EDA genotypes, specific mutations were shown to be
consistently associated with anhidrosis, implying that systematic mapping of
EDA mutations together with the analysis of objective clinical data may help
to distinguish functionally crucial mutations from those allowing residual
activity of the gene product.
explanation: >-
Demonstrates an allelic severity spectrum in which some EDA mutations abolish
sweating and others preserve residual gene-product activity.
treatments:
- name: Temperature Control and Hyperthermia Prevention
description: >-
Maintain access to water and a cool environment during hot weather, avoid
extreme heat, and teach families to recognize and respond promptly to
overheating. These measures are especially important in infancy and childhood.
therapeutic_modality: BEHAVIORAL
treatment_term:
preferred_term: supportive care
term:
id: NCIT:C15747
label: Supportive Care
target_phenotypes:
- preferred_term: Heat intolerance
term:
id: HP:0002046
label: Heat intolerance
target_mechanisms:
- target: Hyperthermia Risk
treatment_effect: INHIBITS
description: >-
Environmental cooling reduces heat accumulation despite deficient evaporative
cooling from sweat.
evidence:
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Access to an adequate water supply and a cool environment during hot weather.
explanation: >-
GeneReviews recommends water access and environmental cooling to prevent overheating.
- name: Dental Rehabilitation
description: >-
Begin dental assessment and treatment early. Options include bonding conical
teeth, orthodontics, age-appropriate prostheses, and implants in selected older
children or adults, with periodic replacement of prostheses as growth proceeds.
treatment_term:
preferred_term: Dental Procedure
term:
id: NCIT:C38052
label: Dental Procedure
target_phenotypes:
- preferred_term: Hypodontia
term:
id: HP:0000668
label: Hypodontia
- preferred_term: Conical tooth
term:
id: HP:0000698
label: Conical tooth
evidence:
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Early dental treatment; bonding of conical teeth; orthodontics as necessary;
dental implants in the anterior portion of the mandibular arch in older
children; replacement of dental prostheses as needed, often every 2.5 years;
dental implants in adults
explanation: >-
GeneReviews specifies age-spanning restorative, orthodontic, prosthetic, and
implant-based dental care.
- name: Skin, Ocular, Nasal, and Respiratory Supportive Care
description: >-
Use emollient and eczema care, lubricating eye drops, ambient humidification to
reduce nasal concretions, and standard management of recurrent respiratory
infections or asthma with specialist referral when needed.
treatment_term:
preferred_term: supportive care
term:
id: NCIT:C15747
label: Supportive Care
target_phenotypes:
- preferred_term: Dry skin
term:
id: HP:0000958
label: Dry skin
- preferred_term: Eczematoid dermatitis
term:
id: HP:0000964
label: Eczematoid dermatitis
- preferred_term: Keratoconjunctivitis sicca
term:
id: HP:0001097
label: Keratoconjunctivitis sicca
- preferred_term: Nasal congestion
term:
id: HP:0001742
label: Nasal congestion
- preferred_term: Recurrent respiratory infections
term:
id: HP:0002205
label: Recurrent respiratory infections
evidence:
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Skin care products for eczema and exposures that exacerbate dry skin.
explanation: >-
GeneReviews recommends skin-directed supportive care.
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Prevention of nasal concretions through humidification of ambient air is
helpful. Lubrication eye drops. Management of recurrent respiratory infections
and asthma per primary care provider with referral to allergist and/or
pulmonologist as needed.
explanation: >-
GeneReviews specifies nasal, ocular, and respiratory supportive measures.
- name: Prenatal EDA1 Replacement Therapy
description: >-
Investigational intra-amniotic recombinant EDA1 replacement has restored sweat
gland development and inducible sweating in a small compassionate-use series.
Six prenatally treated boys have been reported, with normal perspiration persisting
for six years in the two oldest repeatedly treated participants; this remains an
investigational approach under prospective study, not routine standard care.
therapeutic_modality: PROTEIN_REPLACEMENT
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
target_mechanisms:
- target: EDA Ligand Deficiency
treatment_effect: RESTORES
description: >-
Recombinant Fc-EDA supplies the missing ligand during the fetal developmental
window when ectodermal appendages are being specified.
evidence:
- reference: PMID:37108325
reference_title: "A Causal Treatment for X-Linked Hypohidrotic Ectodermal Dysplasia: Long-Term Results of Short-Term Perinatal Ectodysplasin A1 Replacement."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We previously treated nine male patients with obvious signs of XLHED with a
recombinant EDA1 replacement protein, Fc-EDA, either shortly after birth (n =
3) or by prenatal administration in gestational week 26 and beyond (n = 6).
explanation: >-
Directly identifies Fc-EDA as recombinant replacement of the deficient EDA1 ligand.
evidence:
- reference: PMID:29694819
reference_title: "Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We administered this protein intraamniotically to two affected human twins
at gestational weeks 26 and 31 and to a single affected human fetus at
gestational week 26; the infants, born in week 33 (twins) and week 39
(singleton), were able to sweat normally, and XLHED-related illness had not
developed by 14 to 22 months of age.
explanation: >-
Landmark NEJM study demonstrating successful prenatal correction of XLHED
sweat gland deficiency by intra-amniotic EDA1 replacement.
- reference: PMID:37108325
reference_title: "A Causal Treatment for X-Linked Hypohidrotic Ectodermal Dysplasia: Long-Term Results of Short-Term Perinatal Ectodysplasin A1 Replacement."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
prenatal EDA1 replacement resulted in ample sweat gland development and
pilocarpine-inducible sweating in all treated subjects, who also attained more
permanent teeth than their untreated affected relatives. Normal perspiration
has persisted for six years in the two oldest boys treated repeatedly with
Fc-EDA in utero.
explanation: >-
Long-term follow-up confirming permanent correction of sweating ability
after prenatal EDA1 replacement, with additional dental benefit.
notes: >-
Evidence is limited to small nonrandomized treated cohorts. The 2023 follow-up
reports patent holdings and research funding related to the intervention.
- name: Genetic Counseling
description: >-
Explain X-linked transmission after identifying the familial EDA variant. A
heterozygous mother has a 50% chance of transmitting the variant in each
pregnancy; sons who inherit it are affected, while daughters who inherit it are
heterozygous and may manifest features. An affected father transmits the variant
to all daughters and no sons. Prenatal and preimplantation testing are possible
once the familial variant is known.
treatment_term:
preferred_term: Genetic Counseling
term:
id: NCIT:C15240
label: Genetic Counseling
evidence:
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
If the mother of a proband is heterozygous for an EDA pathogenic variant,
the chance of the mother transmitting it in each pregnancy is 50%. If the
father of the proband has an EDA pathogenic variant, he will transmit it to
all his daughters and none of his sons. Males who inherit the pathogenic
variant will be affected; females who inherit the pathogenic variant will be
heterozygous and may show manifestations of ectodermal dysplasia.
explanation: >-
GeneReviews provides the correct per-pregnancy transmission and sex-specific risks.
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Once the EDA, EDAR, EDARADD, or WNT10A pathogenic variant(s) have been
identified in an affected family member, prenatal and preimplantation genetic
testing for HED are possible.
explanation: >-
Supports reproductive testing after molecular identification of the familial variant.
diagnosis:
- name: Clinical Diagnosis After Infancy
description: >-
Classic HED can usually be recognized after infancy from the combination of
deficient sweating, sparse hair, and absent or abnormally shaped teeth.
diagnosis_term:
preferred_term: Diagnostic Procedure
term:
id: NCIT:C18020
label: Diagnostic Procedure
evidence:
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Classic HED can be diagnosed after infancy based on physical features in most
affected individuals.
explanation: >-
GeneReviews establishes the usual clinical diagnostic route and its timing.
- name: Molecular Confirmation of EDA-Related XLHED
description: >-
Identification of a hemizygous pathogenic EDA variant confirms XLHED in an
affected male and distinguishes it from phenotypically overlapping HED caused
by EDAR, EDARADD, or WNT10A.
diagnosis_term:
preferred_term: Molecular Analysis
term:
id: NCIT:C19770
label: Molecular Analysis
evidence:
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Identification of a hemizygous EDA pathogenic variant in an affected male or
biallelic EDAR, EDARADD, or WNT10A pathogenic variants in an affected male or
female confirms the diagnosis.
explanation: >-
Defines the molecular confirmation criterion and the major alternative genes.
- name: Phenotype-Guided Molecular Testing and EDA Copy-Number Findings
description: >-
In a small mixed ectodermal-dysplasia cohort, classic symptoms supported targeted
EDA/EDAR sequencing, whereas whole-exome sequencing was considered effective when
those symptoms were absent. Copy-number variations occurred in 23.1% (3/13) of
EDA-positive cases, showing that the reported EDA-positive molecular findings were
not limited to sequence variants. This cohort-specific proportion is not an XLHED
population prevalence estimate.
diagnosis_term:
preferred_term: Molecular Analysis
term:
id: NCIT:C19770
label: Molecular Analysis
evidence:
- reference: PMID:39244550
reference_title: Genetic profiling and diagnostic strategies for patients with ectodermal dysplasias in Korea.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Notably, 23.1% (3/13) of EDA-positive cases exhibited copy number variations.
explanation: >-
Demonstrates that EDA-positive findings in this cohort included copy-number
variation as well as sequence variants.
- reference: PMID:39244550
reference_title: Genetic profiling and diagnostic strategies for patients with ectodermal dysplasias in Korea.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
When conducting molecular diagnostics for ED, opting for targeted sequencing
of EDA/EDAR mutations is advisable for cases with classical symptoms, while WES
is deemed an effective strategy for cases in which these symptoms are absent.
explanation: >-
Supports targeted EDA/EDAR testing with classical symptoms and whole-exome
sequencing when those symptoms are absent.
- name: Quantitative Sweat-Gland Function Assessment
description: >-
Pilocarpine-induced sweat volume, palmar sweat-pore density, and basal and
stimulated skin conductance can objectively quantify sweat-gland dysfunction.
These measurements are useful supportive biomarkers but do not determine the
causal gene.
evidence:
- reference: PMID:21357618
reference_title: Sweating ability and genotype in individuals with X-linked hypohidrotic ectodermal dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In 36 genotyped XLHED patients and 29 control subjects aged 0-57 years,
pilocarpine-induced sweat volume, palmar sweat pore density, and palmar skin
conductance before and after stimulation were determined.
explanation: >-
Specifies three noninvasive quantitative measures evaluated in genotyped XLHED.
- reference: PMID:21357618
reference_title: Sweating ability and genotype in individuals with X-linked hypohidrotic ectodermal dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
this study confirmed a consistent, quantifiable defect of sweat gland function
in male XLHED subjects as a disease biomarker.
explanation: >-
Supports quantitative sweat-gland dysfunction as an objective disease biomarker.
differential_diagnoses:
- name: Autosomal Hypohidrotic Ectodermal Dysplasia
description: >-
EDAR-, EDARADD-, and WNT10A-related HED can reproduce the classic hair, sweat,
and dental triad and may be clinically indistinguishable from XLHED.
distinguishing_features:
- Biallelic EDAR, EDARADD, or WNT10A pathogenic variants support autosomal recessive HED rather than EDA-related XLHED.
- Heterozygous EDAR, EDARADD, or WNT10A variants can establish mild autosomal HED.
- A pedigree with father-to-son transmission excludes X-linked inheritance.
evidence:
- reference: PMID:20301291
reference_title: Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Identification of a hemizygous EDA pathogenic variant in an affected male or
biallelic EDAR, EDARADD, or WNT10A pathogenic variants in an affected male or
female confirms the diagnosis. The diagnosis of mild HED is established in a
female by identification of a heterozygous EDA, EDAR, EDARADD, or WNT10A
pathogenic variant. The diagnosis of mild HED is established in a male by
identification of a heterozygous EDAR, EDARADD, or WNT10A pathogenic variant.
explanation: >-
GeneReviews defines the overlapping genetic diagnoses and the variant states
that distinguish them.
- name: IKBKG-Related Immunodeficiency With or Without Ectodermal Dysplasia
disease_term:
preferred_term: IKBKG-related immunodeficiency with or without ectodermal dysplasia
term:
id: MONDO:0100162
label: IKBKG-related immunodeficiency with or without ectodermal dysplasia
description: >-
Hypomorphic IKBKG (NEMO) variants can cause an X-linked ectodermal-dysplasia
phenotype through impaired NF-kappaB signaling, overlapping XLHED clinically
and mechanistically, but with clinically important immunodeficiency.
distinguishing_features:
- Dysgammaglobulinemia and severe or recurrent infections favor IKBKG-related disease.
- A pathogenic IKBKG variant, rather than an EDA variant, establishes this diagnosis.
evidence:
- reference: PMID:11047757
reference_title: A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Affected males manifest dysgammaglobulinemia and, despite therapy, have
significant morbidity and mortality from recurrent infections.
explanation: >-
Identifies the immune phenotype that distinguishes IKBKG-related HED-ID from XLHED.
- reference: PMID:11047757
reference_title: A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The findings define a new X-linked recessive immunodeficiency syndrome,
distinct from other types of HED and immunodeficiency syndromes.
explanation: >-
Establishes HED-ID as a distinct X-linked immunodeficiency syndrome.
animal_models:
- species: Mouse (Mus musculus)
genotype: Eda mutation with prenatal exposure to recombinant receptor-binding EDA protein
genes:
- preferred_term: EDA
term:
id: hgnc:3157
label: EDA
description: >-
Eda-mutant mouse fetuses underwent normal development after in-utero exposure
to recombinant EDA containing the receptor-binding domain. The rescue supports
EDA ligand deficiency as causal and demonstrates a prenatal developmental window
for replacement therapy, while not by itself establishing human efficacy or safety.
associated_phenotypes:
- Prenatal rescue of Eda-associated ectodermal developmental defects
evidence:
- reference: PMID:29694819
reference_title: Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
We observed normal development of mouse fetuses with Eda mutations after they
had been exposed in utero to a recombinant protein that includes the
receptor-binding domain of EDA.
explanation: >-
Directly documents prenatal phenotypic rescue in the Eda-mutant mouse model.
clinical_trials:
- name: NCT04980638
phase: PHASE_II
description: >-
Prospective, open-label, genotype-match-controlled, nonrandomized,
multicenter international phase 2 trial investigating the efficacy and safety
of intra-amniotic ER004 as prenatal treatment for unborn male subjects with XLHED.
target_phenotypes:
- preferred_term: Hypohidrosis
term:
id: HP:0000966
label: Hypohidrosis
evidence:
- reference: clinicaltrials:NCT04980638
reference_title: "A Prospective, Open-label, Genotype-match Controlled, Multicenter Clinical Trial to Investigate the Efficacy and Safety of Intra-amniotic ER004 as a Prenatal Treatment for Male Subjects With XLHED"
supports: SUPPORT
snippet: >-
This is an open-label, prospective, genotype-match controlled for primary
estimand, non randomized, multicenter, international Phase 2 clinical trial
designed to investigate the efficacy and safety of ER004 administered
intraamniotically as a treatment for unborn XLHED male subjects.
explanation: >-
The cached official registry summary supports the trial design, phase,
intervention route, study population, and efficacy and safety objectives.
datasets: []
X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare developmental genetic disorder classically defined by the triad of hypotrichosis, hypohidrosis/anhidrosis, and hypodontia/oligodontia, reflecting abnormal formation of ectodermal appendages (hair follicles, eccrine sweat glands, teeth) due to deficiency of ectodysplasin A1 (EDA1) signaling. (aftab2023xlinkedhypohidroticectodermal pages 1-2, callea2022extendedoverviewof pages 2-4)
A key 2024 advance is improved molecular diagnostic strategy evidence supporting phenotype-guided targeted sequencing (EDA/EDAR) for “classical triad” presentations and exome-scale testing for atypical cases, with copy-number variation (CNV) detection as an important contributor to missed diagnoses. (kim2024geneticprofilingand pages 1-2, kim2024geneticprofilingand pages 7-8)
A major translational development is prenatal protein replacement for affected male fetuses using intra-amniotic delivery of an EDA1 replacement (Fc-EDA/EDI200; and a next-generation molecule ER004), with human compassionate-use data showing sustained restoration of sweating and ongoing multicenter trials (EDELIFE, NCT04980638). (schneider2018prenatalcorrectionof pages 3-5, NCT04980638 chunk 1)
XLHED is a genetic ectodermal dysplasia in which deficiency of ectodysplasin A (EDA/EDA1) signaling disrupts epithelial–mesenchymal interactions required for appendage development, producing reduced/absent sweat glands (heat intolerance, risk of hyperthermia), sparse hair, and missing/abnormal teeth; additional recurrent respiratory, skin, and ocular complications are common. (aftab2023xlinkedhypohidroticectodermal pages 1-2, fete2014x‐linkedhypohidroticectodermal pages 2-4)
Abstract-supported definition (direct quote): XLHED is “diagnosed by the triad of decreased sweating, reduced hair, and hypodontia.” (fete2014x‐linkedhypohidroticectodermal pages 1-2)
| Disease name | Common synonyms / alternative names | MONDO | OMIM/MIM disease # | Causal gene OMIM IDs | ICD-10 | MeSH mapping noted in ClinicalTrials.gov |
|---|---|---|---|---|---|---|
| X-linked hypohidrotic ectodermal dysplasia (XLHED) | Christ-Siemens-Touraine syndrome; X-linked HED; anhidrotic/hypohidrotic ectodermal dysplasia (aftab2023xlinkedhypohidroticectodermal pages 1-2, callea2022extendedoverviewof pages 2-4, fete2014x‐linkedhypohidroticectodermal pages 1-2) | MONDO:0010585 / MONDO_0010585 (NCT04980638 chunk 2) | MIM/OMIM: 305100 (nguyennielsen2013theprevalenceof pages 1-2, callea2022extendedoverviewof pages 2-4, schneider2018prenatalcorrectionof pages 1-2) | EDA: MIM 300451; EDAR: MIM 604095; EDARADD: MIM 606603 (nguyennielsen2013theprevalenceof pages 1-2, callea2022extendedoverviewof pages 2-4) | Q82.4 “Ectodermal Dysplasia (Anhidrotic)” used in Danish registry study for clinically diagnosed HED/XLHED ascertainment (nguyennielsen2013theprevalenceof pages 1-2, nguyennielsen2013theprevalenceof pages 2-3) | “Ectodermal Dysplasia 1, Anhidrotic” (MeSH D053358) in NCT04980638 / EDELIFE record (NCT04980638 chunk 2) |
Table: This table compiles the main nomenclature and database identifiers for X-linked hypohidrotic ectodermal dysplasia, including disease and gene OMIM numbers, MONDO, ICD-10, and MeSH. It is useful for harmonizing disease records across clinical, ontology, and literature sources.
Evidence source type note: identifiers are derived from aggregated disease resources (registry-based epidemiology and patient registries), and trial registries (ClinicalTrials.gov), rather than individual EHR-only sources. (nguyennielsen2013theprevalenceof pages 1-2, fete2014x‐linkedhypohidroticectodermal pages 1-2, NCT04980638 chunk 1)
Primary cause: pathogenic loss-of-function variants in EDA (ectodysplasin A; EDA1 isoform) causing deficiency of EDA1 signaling, inherited in an X-linked manner in XLHED. (schneider2022ectodermaldysplasiasnew pages 1-2, nguyennielsen2013theprevalenceof pages 1-2)
Related hypohidrotic ectodermal dysplasia genes (non-X-linked forms): EDAR, EDARADD, WNT10A are frequently implicated in hypohidrotic ED broadly (with EDAR/EDARADD capable of dominant or recessive forms; WNT10A often recessive). (aftab2023xlinkedhypohidroticectodermal pages 1-2, kovalskaia2023molecularbasisand pages 1-2)
The principal risk factor is carriage of a pathogenic EDA variant in a family (X-linked inheritance), with males generally more severely affected and females showing variable expressivity. (aftab2023xlinkedhypohidroticectodermal pages 1-2, fete2014x‐linkedhypohidroticectodermal pages 2-4)
No specific genetic or environmental protective factors were identified in the retrieved primary sources.
Direct gene–environment interaction evidence (formal GxE) was not identified in the retrieved sources. Clinically, environmental heat exposure interacts with anhidrosis to precipitate hyperthermia risk (a clinically important interaction, though not studied as GxE). (schneider2018prenatalcorrectionof pages 1-2, nguyennielsen2013theprevalenceof pages 1-2)
Below are major phenotypes (symptoms/signs) with suggested HPO terms and evidence.
1) Hypohidrosis/anhidrosis and heat intolerance - Type: clinical sign/functional deficit - Onset: typically infancy/early childhood (early clinical recognition), though diagnosis may be delayed. (nguyennielsen2013theprevalenceof pages 1-2, aftab2023xlinkedhypohidroticectodermal pages 1-2) - Severity: ranges from absent sweating to low residual sweating depending on genotype. (schneider2011sweatingabilityand pages 5-10) - Key complications: life-threatening hyperthermia. (schneider2018prenatalcorrectionof pages 1-2) - Suggested HPO: HP:0000973 (Anhidrosis), HP:0003214 (Hypohidrosis), HP:0002044 (Hyperthermia), HP:0004370 (Heat intolerance) - Quantitative biomarker data (sweat testing): in controls, mean pilocarpine-stimulated sweat volume was 72 µL (range 29–93 µL) and mean sweat pore density 455 pores/cm² (294–900). In XLHED males, 14/31 had no pores/no inducible sweating; 7/31 produced 1–11 µL (low sweating). (schneider2011sweatingabilityand pages 5-10, schneider2011sweatingabilityand pages 1-5)
2) Hypodontia/oligodontia (abnormal or missing teeth) - Type: physical manifestation - Onset: developmental (childhood; detection with tooth development) - Frequency (registry-reported): hypodontia reported in 89% overall of XLHED respondents in EDIR, and in 74% of male XLHED registrants in one registry analysis. (fete2014x‐linkedhypohidroticectodermal pages 1-2) - Suggested HPO: HP:0000668 (Hypodontia), HP:0000674 (Oligodontia), HP:0006480 (Abnormality of dental morphology)
3) Hypotrichosis / sparse scalp hair and eyebrows - Type: physical manifestation - Frequency (registry-reported): reduced hair reported in 74% overall in EDIR and 80% of male XLHED registrants; in females, hair abnormalities still reported by the majority (63% in EDIR). (fete2014x‐linkedhypohidroticectodermal pages 1-2, fete2014x‐linkedhypohidroticectodermal pages 2-4) - Suggested HPO: HP:0001006 (Hypotrichosis), HP:0000535 (Sparse eyebrow)
4) Recurrent respiratory/nasal complications - Type: symptoms/clinical signs - Frequency (international patient registry, males): foul-smelling nasal discharge 67%, infections requiring antibiotics 52%, recurrent pneumonias 19%, wheeze 66%, recurrent sinusitis 49%, raspy/hoarse voice 67%. (fete2014x‐linkedhypohidroticectodermal pages 2-4) - Suggested HPO: HP:0002789 (Recurrent respiratory infections), HP:0001742 (Chronic sinusitis), HP:0002099 (Wheezing), HP:0001609 (Hoarse voice), HP:0011950 (Nasal discharge)
5) Eczema / dry skin - Type: clinical sign - Frequency (EDIR): eczema reported in 66% males and 40% females in registry summary excerpt. (fete2014x‐linkedhypohidroticectodermal pages 1-2) - Suggested HPO: HP:0000964 (Eczema), HP:0000958 (Dry skin)
6) Ocular surface disease / dry eye - Type: symptom/clinical sign - Frequency: “nearly one-third” affected with ocular dry eye in registry excerpt. (fete2014x‐linkedhypohidroticectodermal pages 2-4) - Suggested HPO: HP:0001097 (Dry eye), HP:0000508 (Photophobia) (frequently associated per ocular review context) (callea2022extendedoverviewof pages 2-4)
Quality of life is substantially impacted through heat avoidance/thermoregulation constraints, need for long-term dental rehabilitation, recurrent ENT/respiratory issues, and ocular surface disease requiring surveillance and ongoing supportive care. (aftab2023xlinkedhypohidroticectodermal pages 8-9, callea2022extendedoverviewof pages 2-4, fete2014x‐linkedhypohidroticectodermal pages 2-4)
Variant classes: deletions, nonsense, frameshift, splice-site, and missense variants affecting key functional domains (furin cleavage site, TNF homology domain, collagen-like repeats) correlate with absent versus residual sweating. (schneider2011sweatingabilityand pages 5-10)
Genotype–phenotype mapping (example evidence): missense variants disrupting the furin recognition site (R153C/R155C/R156H) and certain TNF-domain mutations (e.g., Y304C) are linked to anhidrosis, whereas some variants (e.g., V262F, R276C, G299R, R69L) can be associated with residual sweating. (schneider2011sweatingabilityand pages 5-10)
Female heterozygotes can have clinically significant symptoms with high variability (variable expressivity). (fete2014x‐linkedhypohidroticectodermal pages 2-4)
Evidence for specific modifier genes was not identified in the retrieved sources; however, the 2024 Korean cohort emphasizes that phenotype (complete triad vs incomplete) strongly predicts detection of EDA/EDAR mutations, suggesting clinical heterogeneity may partly reflect genetic heterogeneity and structural variants (CNVs). (kim2024geneticprofilingand pages 7-8, kim2024geneticprofilingand pages 1-2)
Explicit epigenetic mechanisms for XLHED were not identified in the retrieved sources.
Large deletions/CNVs affecting EDA contribute to disease and can be missed without CNV-aware analysis (e.g., MLPA/WGS). In the 2024 Korean ED cohort, 23.1% (3/13) of EDA-positive cases had CNVs. (kim2024geneticprofilingand pages 1-2)
No specific toxin/lifestyle/infectious causal factors were identified; the disease is primarily genetic. Key environmental management issue is heat exposure, which is clinically dangerous in anhidrotic patients. (schneider2018prenatalcorrectionof pages 1-2)
1) Upstream trigger: germline pathogenic EDA variant → deficiency of functional EDA1 ligand. (schneider2018prenatalcorrectionof pages 1-2) 2) Signal transduction: EDA1 binds EDAR, recruits EDARADD, and activates a TNF-like signaling cascade culminating in NF-κB activation. (callea2022extendedoverviewof pages 2-4) 3) Developmental consequence: impaired epithelial–mesenchymal signaling in placodes → failed/aborted development of ectodermal appendages (eccrine sweat glands, teeth, hair follicles, meibomian glands). (callea2022extendedoverviewof pages 2-4, schneider2018prenatalcorrectionof pages 1-2) 4) Clinical manifestations: anhidrosis/hypohidrosis → heat intolerance/hyperthermia risk; hypodontia/oligodontia → chewing/speech/esthetic impacts; hypotrichosis; frequent ENT/respiratory problems likely related to glandular/epithelial abnormalities. (fete2014x‐linkedhypohidroticectodermal pages 2-4, schneider2018prenatalcorrectionof pages 1-2)
Human eccrine sweat gland morphogenesis has a defined fetal window: “key developmental events” occur in gestational weeks 20–30, motivating prenatal replacement therapy to rescue sweat gland formation. (schneider2022ectodermaldysplasiasnew pages 2-4)
Mechanistic synthesis from recent literature indicates reciprocal reinforcement between EDA–EDAR–NF-κB signaling and WNT/β-catenin activity during placode development (e.g., Wnt10b as an NF-κB target; Wnt signaling upregulating Edar). This is commonly inferred from mouse developmental and single-cell analyses and provides a plausible mechanism linking EDA deficiency to broader appendage patterning defects. (jakhar2025interplaybetweenedaedar pages 5-7, jakhar2025interplaybetweenedaedar pages 2-4)
(These are ontology suggestions aligned with the mechanisms described in the cited sources. (callea2022extendedoverviewof pages 2-4, schneider2022ectodermaldysplasiasnew pages 2-4, jakhar2025interplaybetweenedaedar pages 2-4))
Not specifically addressed in the retrieved sources beyond EDA being a transmembrane TNF-family ligand that is cleaved and released (a secreted signaling moiety). (schneider2022ectodermaldysplasiasnew pages 2-4)
Clinical manifestations often begin in infancy/early childhood; one clinical summary reports symptom onset between “one month to 23 months.” (aftab2023xlinkedhypohidroticectodermal pages 1-2)
The disease is lifelong; some severe early-life risks (hyperthermia) can be mitigated with recognition and management. Registry data describe “life-long XLHED clinical complications” such as sinus infections, eczema, wheezing, and hoarse voice. (fete2014x‐linkedhypohidroticectodermal pages 1-2)
Predominantly X-linked (males more severely affected; females variably affected). (aftab2023xlinkedhypohidroticectodermal pages 1-2, fete2014x‐linkedhypohidroticectodermal pages 2-4)
Expert interpretation: the very large difference between molecularly confirmed prevalence and broader algorithm-defined HED prevalence implies substantial under-confirmation (genetic testing gaps) and/or misclassification when relying on administrative codes alone, supporting current emphasis on molecular confirmation and CNV-aware testing. (nguyennielsen2013theprevalenceof pages 1-2, kim2024geneticprofilingand pages 1-2)
Diagnosis is often based on the triad (sweat, hair, teeth) and characteristic facies/complications. (fete2014x‐linkedhypohidroticectodermal pages 1-2, aftab2023xlinkedhypohidroticectodermal pages 1-2)
Pilocarpine-induced sweat testing plus sweat pore density assessment is a quantifiable biomarker approach. - In Schneider et al. (2011), sweat pore count sensitivity for identifying affected males was 94% in children and 92% in adults, with clear quantitative separation from controls. (schneider2011sweatingabilityand pages 5-10) - Controls showed mean sweat volume 72 µL and mean sweat pore density 455 pores/cm², whereas many XLHED males had absent pores and 0 sweat, and low-sweating males produced 1–11 µL. (schneider2011sweatingabilityand pages 5-10, schneider2011sweatingabilityand pages 1-5)
2024 cohort evidence (Korea, Orphanet J Rare Dis; published 2024-09-?? per journal issue metadata): - Overall diagnostic yield: 74.1% (20/27) mutation-positive. (kim2024geneticprofilingand pages 1-2) - Among positives, 80% (16/20) had EDA or EDAR mutations; 23.1% (3/13) of EDA-positive cases had CNVs. (kim2024geneticprofilingand pages 1-2) - Phenotype predicts yield: 94.1% of patients with the complete triad (hair/skin/dental) had detectable EDA/EDAR mutations, vs 0% when those three symptoms were not all present. (kim2024geneticprofilingand pages 7-8, kim2024geneticprofilingand pages 1-2)
Direct abstract quote (diagnostic strategy conclusion): “When conducting molecular diagnostics for ED, opting for targeted sequencing of EDA/EDAR mutations is advisable for cases with classical symptoms, while WES is deemed an effective strategy for cases in which these symptoms are absent.” (kim2024geneticprofilingand pages 1-2)
Prenatal ultrasound-based tooth germ counting can support non-invasive fetal assessment in at-risk pregnancies; this approach is used in trial screening and was part of the diagnostic workup for prenatal therapy. (schneider2022ectodermaldysplasiasnew pages 1-2, schneider2018prenatalcorrectionof pages 1-2)
A case-based review highlights the need to distinguish XLHED from other ectodermal dysplasias and syndromes (e.g., EEC syndrome) and acquired hypohidrosis causes, emphasizing clinical and molecular confirmation. (aftab2023xlinkedhypohidroticectodermal pages 8-9)
In EDIR registry analysis, 21% of XLHED registrants reported a family history of infant or childhood deaths, stated as consistent with published mortality data. (fete2014x‐linkedhypohidroticectodermal pages 1-2)
Current routine care is largely supportive and preventive, including thermoregulation/heat avoidance strategies, dental rehabilitation (prosthodontics/implants), dermatologic management (eczema/dry skin), ENT/pulmonary management for recurrent infections, and ophthalmic care for dry eye/ocular surface disease. (aftab2023xlinkedhypohidroticectodermal pages 8-9, callea2022extendedoverviewof pages 2-4)
Suggested MAXO terms (examples): supportive care; dental prosthesis placement; management of hyperthermia; skin emollient therapy; artificial tears / ocular surface lubrication; respiratory infection prevention.
Schneider et al. (NEJM, 2018-04-26) reported intra-amniotic administration of Fc-EDA (EDI200) to 3 affected male fetuses. - Dosing (twins): 100 mg/kg estimated fetal body weight at gestational week 26 and again at week 31. (schneider2018prenatalcorrectionof pages 3-5) - Evidence of fetal uptake: cord-blood Fc-EDA measurable 7 days after administration (62.4 and 932 ng/mL). (schneider2018prenatalcorrectionof pages 3-5) - Efficacy endpoints: treated infants had normal sweat-duct density and “normal pilocarpine-induced sweating at 6 months,” with no hyperthermic episodes or respiratory-related hospitalizations over 22 months in the twin case. (schneider2018prenatalcorrectionof pages 3-5) - Quote (author conclusion): “Prenatal treatment with Fc-EDA restored sustained sweating ability in human patients with EDA mutations that abrogate perspiration.” (schneider2018prenatalcorrectionof pages 5-7)
Visual evidence: Figure 1 from the NEJM report shows the contrast between untreated XLHED (no sweat pores/0 µL sweat) and treated infant vs healthy control for sweat pores and sweat volume outcomes. (schneider2018prenatalcorrectionof media 9c02cda0)
A translational review notes that postnatal dosing in infants did not successfully induce sweat ducts or sweating, consistent with a restricted developmental window for eccrine gland morphogenesis. (schneider2022ectodermaldysplasiasnew pages 2-4)
ClinicalTrials.gov describes ER004 as an “EDA1 replacement” designed for high-affinity EDAR binding. - Design: Phase 2, open-label, genotype-match controlled; 3 intra-amniotic injections ~3 weeks apart starting gestational week 26 at 100 mg/kg estimated fetal weight per injection. (NCT04980638 chunk 1) - Primary endpoint: mean sweat volume at 6 months (pilocarpine-induced). (NCT04980638 chunk 1) - Secondary endpoints include: sweat pore density, dental development, meibomian glands, ocular outcomes, hospitalizations for hyperthermia/infections. (NCT04980638 chunk 1)
Expert analysis: the trial’s inclusion of objective sweating endpoints (sweat volume and pore density) and longer follow-up (to age 5) directly addresses prior limitations of early small compassionate-use series and aligns with validated sweat biomarkers (pilocarpine iontophoresis, pore counts) used in genotype–phenotype work. (NCT04980638 chunk 1, schneider2011sweatingabilityand pages 5-10)
No primary prevention exists for germline XLHED beyond reproductive options.
Key complication prevention includes early diagnosis, anticipatory guidance for fever/heat exposure, and early dental/ENT/ophthalmic interventions to prevent downstream morbidity. (aftab2023xlinkedhypohidroticectodermal pages 8-9, callea2022extendedoverviewof pages 2-4)
Given X-linked inheritance and severe male phenotype, cascade testing and counseling are central. Prenatal ultrasound screening (tooth germ assessment) is used clinically and in trial screening as a non-invasive diagnostic tool in at-risk pregnancies. (schneider2022ectodermaldysplasiasnew pages 1-2, schneider2018prenatalcorrectionof pages 1-2)
Naturally occurring EDA-related hypohidrotic ectodermal dysplasia has been reported across species, supporting conserved biology. - Cat (first report, 2024-06): a male cat with alopecia and tooth anomalies had a hemizygous EDA missense variant; the paper notes EDA loss-of-function variants cause HED in humans, mice, dogs, and cattle and extends this to cats. (rietmann2024edamissensevariant pages 1-2) - Cattle (historic): evidence cited for bovine anhidrotic ED caused by deletion of exon 3 of the bovine ED1 gene (EDA ortholog). (rietmann2024edamissensevariant pages 2-4)
NCBI Taxonomy identifiers were not provided in the retrieved excerpts.
The Tabby mouse is a canonical model of EDA deficiency used to study ectodermal appendage development and therapeutic rescue by prenatal EDA replacement; mechanistic work in the NEJM report also used Eda-deficient mice to show neonatal Fc receptor–dependent fetal uptake after intra-amniotic therapy. (schneider2018prenatalcorrectionof pages 2-3, schneider2018prenatalcorrectionof pages 3-5)
Dog models of XLHED have been used for prenatal recombinant EDA1 administration, with improvements reported across multiple ectodermal structures, supporting translational relevance to prenatal therapy. (aftab2023xlinkedhypohidroticectodermal pages 8-9)
References
(aftab2023xlinkedhypohidroticectodermal pages 1-2): Hammad Aftab, Ivan A Escudero, and Fatin Sahhar. X-linked hypohidrotic ectodermal dysplasia (xlhed): a case report and overview of the diagnosis and multidisciplinary modality treatments. Cureus, Jun 2023. URL: https://doi.org/10.7759/cureus.40383, doi:10.7759/cureus.40383. This article has 10 citations.
(callea2022extendedoverviewof pages 2-4): Michele Callea, Stefano Bignotti, Francesco Semeraro, Francisco Cammarata-Scalisi, Jinia El-Feghaly, Antonino Morabito, Vito Romano, and Colin E. Willoughby. Extended overview of ocular phenotype with recent advances in hypohidrotic ectodermal dysplasia. Children, 9:1357, Sep 2022. URL: https://doi.org/10.3390/children9091357, doi:10.3390/children9091357. This article has 9 citations.
(kim2024geneticprofilingand pages 1-2): Man Jin Kim, Jee-Soo Lee, Seung Won Chae, Sung Im Cho, Jangsup Moon, Jung Min Ko, Jong-Hee Chae, and Moon-Woo Seong. Genetic profiling and diagnostic strategies for patients with ectodermal dysplasias in korea. Orphanet Journal of Rare Diseases, Sep 2024. URL: https://doi.org/10.1186/s13023-024-03331-6, doi:10.1186/s13023-024-03331-6. This article has 1 citations and is from a peer-reviewed journal.
(kim2024geneticprofilingand pages 7-8): Man Jin Kim, Jee-Soo Lee, Seung Won Chae, Sung Im Cho, Jangsup Moon, Jung Min Ko, Jong-Hee Chae, and Moon-Woo Seong. Genetic profiling and diagnostic strategies for patients with ectodermal dysplasias in korea. Orphanet Journal of Rare Diseases, Sep 2024. URL: https://doi.org/10.1186/s13023-024-03331-6, doi:10.1186/s13023-024-03331-6. This article has 1 citations and is from a peer-reviewed journal.
(schneider2018prenatalcorrectionof pages 3-5): Holm Schneider, Florian Faschingbauer, Sonia Schuepbach-Mallepell, Iris Körber, Sigrun Wohlfart, Angela Dick, Mandy Wahlbuhl, Christine Kowalczyk-Quintas, Michele Vigolo, Neil Kirby, Corinna Tannert, Oliver Rompel, Wolfgang Rascher, Matthias W. Beckmann, and Pascal Schneider. Prenatal correction of x-linked hypohidrotic ectodermal dysplasia. New England Journal of Medicine, 378:1604-1610, Apr 2018. URL: https://doi.org/10.1056/nejmoa1714322, doi:10.1056/nejmoa1714322. This article has 219 citations and is from a highest quality peer-reviewed journal.
(NCT04980638 chunk 1): Intraamniotic Administrations of ER004 to Male Subjects With X-linked Hypohidrotic Ectodermal Dysplasia. EspeRare Foundation. 2022. ClinicalTrials.gov Identifier: NCT04980638
(fete2014x‐linkedhypohidroticectodermal pages 2-4): Mary Fete, Julie Hermann, Jeffrey Behrens, and Kenneth M. Huttner. X‐linked hypohidrotic ectodermal dysplasia (xlhed): clinical and diagnostic insights from an international patient registry. American Journal of Medical Genetics Part A, 164:2437-2442, Oct 2014. URL: https://doi.org/10.1002/ajmg.a.36436, doi:10.1002/ajmg.a.36436. This article has 72 citations.
(fete2014x‐linkedhypohidroticectodermal pages 1-2): Mary Fete, Julie Hermann, Jeffrey Behrens, and Kenneth M. Huttner. X‐linked hypohidrotic ectodermal dysplasia (xlhed): clinical and diagnostic insights from an international patient registry. American Journal of Medical Genetics Part A, 164:2437-2442, Oct 2014. URL: https://doi.org/10.1002/ajmg.a.36436, doi:10.1002/ajmg.a.36436. This article has 72 citations.
(NCT04980638 chunk 2): Intraamniotic Administrations of ER004 to Male Subjects With X-linked Hypohidrotic Ectodermal Dysplasia. EspeRare Foundation. 2022. ClinicalTrials.gov Identifier: NCT04980638
(nguyennielsen2013theprevalenceof pages 1-2): Mary Nguyen-Nielsen, Stine Skovbo, Dea Svaneby, Lars Pedersen, and Jon Fryzek. The prevalence of x-linked hypohidrotic ectodermal dysplasia (xlhed) in denmark, 1995-2010. European journal of medical genetics, 56 5:236-42, May 2013. URL: https://doi.org/10.1016/j.ejmg.2013.01.012, doi:10.1016/j.ejmg.2013.01.012. This article has 97 citations and is from a peer-reviewed journal.
(schneider2018prenatalcorrectionof pages 1-2): Holm Schneider, Florian Faschingbauer, Sonia Schuepbach-Mallepell, Iris Körber, Sigrun Wohlfart, Angela Dick, Mandy Wahlbuhl, Christine Kowalczyk-Quintas, Michele Vigolo, Neil Kirby, Corinna Tannert, Oliver Rompel, Wolfgang Rascher, Matthias W. Beckmann, and Pascal Schneider. Prenatal correction of x-linked hypohidrotic ectodermal dysplasia. New England Journal of Medicine, 378:1604-1610, Apr 2018. URL: https://doi.org/10.1056/nejmoa1714322, doi:10.1056/nejmoa1714322. This article has 219 citations and is from a highest quality peer-reviewed journal.
(nguyennielsen2013theprevalenceof pages 2-3): Mary Nguyen-Nielsen, Stine Skovbo, Dea Svaneby, Lars Pedersen, and Jon Fryzek. The prevalence of x-linked hypohidrotic ectodermal dysplasia (xlhed) in denmark, 1995-2010. European journal of medical genetics, 56 5:236-42, May 2013. URL: https://doi.org/10.1016/j.ejmg.2013.01.012, doi:10.1016/j.ejmg.2013.01.012. This article has 97 citations and is from a peer-reviewed journal.
(schneider2022ectodermaldysplasiasnew pages 1-2): Holm Schneider. Ectodermal dysplasias: new perspectives on the treatment of so far immedicable genetic disorders. Frontiers in Genetics, Sep 2022. URL: https://doi.org/10.3389/fgene.2022.1000744, doi:10.3389/fgene.2022.1000744. This article has 27 citations and is from a peer-reviewed journal.
(kovalskaia2023molecularbasisand pages 1-2): V. A. Kovalskaia, T. Cherevatova, A. V. Polyakov, and O. P. Ryzhkova. Molecular basis and genetics of hypohidrotic ectodermal dysplasias. Vavilov Journal of Genetics and Breeding, 27:676-683, Nov 2023. URL: https://doi.org/10.18699/vjgb-23-78, doi:10.18699/vjgb-23-78. This article has 6 citations.
(schneider2011sweatingabilityand pages 5-10): Holm Schneider, Johanna Hammersen, Sabine Preisler-Adams, Kenneth Huttner, Wolfgang Rascher, and Axel Bohring. Sweating ability and genotype in individuals with x-linked hypohidrotic ectodermal dysplasia. Journal of Medical Genetics, 48:426-432, Feb 2011. URL: https://doi.org/10.1136/jmg.2010.084012, doi:10.1136/jmg.2010.084012. This article has 70 citations and is from a domain leading peer-reviewed journal.
(schneider2011sweatingabilityand pages 1-5): Holm Schneider, Johanna Hammersen, Sabine Preisler-Adams, Kenneth Huttner, Wolfgang Rascher, and Axel Bohring. Sweating ability and genotype in individuals with x-linked hypohidrotic ectodermal dysplasia. Journal of Medical Genetics, 48:426-432, Feb 2011. URL: https://doi.org/10.1136/jmg.2010.084012, doi:10.1136/jmg.2010.084012. This article has 70 citations and is from a domain leading peer-reviewed journal.
(aftab2023xlinkedhypohidroticectodermal pages 8-9): Hammad Aftab, Ivan A Escudero, and Fatin Sahhar. X-linked hypohidrotic ectodermal dysplasia (xlhed): a case report and overview of the diagnosis and multidisciplinary modality treatments. Cureus, Jun 2023. URL: https://doi.org/10.7759/cureus.40383, doi:10.7759/cureus.40383. This article has 10 citations.
(schneider2022ectodermaldysplasiasnew pages 2-4): Holm Schneider. Ectodermal dysplasias: new perspectives on the treatment of so far immedicable genetic disorders. Frontiers in Genetics, Sep 2022. URL: https://doi.org/10.3389/fgene.2022.1000744, doi:10.3389/fgene.2022.1000744. This article has 27 citations and is from a peer-reviewed journal.
(jakhar2025interplaybetweenedaedar pages 5-7): Ajay Jakhar, Konrad Łukaszyk, Anna Pulawska-Czub, and Krzysztof Kobielak. Interplay between eda-edar and wnt signalling pathways in the development of skin appendages in hypohidrotic ectodermal dysplasia. Pediatria i Medycyna Rodzinna, 21:51-58, Apr 2025. URL: https://doi.org/10.15557/pimr.2025.0006, doi:10.15557/pimr.2025.0006. This article has 3 citations.
(jakhar2025interplaybetweenedaedar pages 2-4): Ajay Jakhar, Konrad Łukaszyk, Anna Pulawska-Czub, and Krzysztof Kobielak. Interplay between eda-edar and wnt signalling pathways in the development of skin appendages in hypohidrotic ectodermal dysplasia. Pediatria i Medycyna Rodzinna, 21:51-58, Apr 2025. URL: https://doi.org/10.15557/pimr.2025.0006, doi:10.15557/pimr.2025.0006. This article has 3 citations.
(schneider2018prenatalcorrectionof pages 5-7): Holm Schneider, Florian Faschingbauer, Sonia Schuepbach-Mallepell, Iris Körber, Sigrun Wohlfart, Angela Dick, Mandy Wahlbuhl, Christine Kowalczyk-Quintas, Michele Vigolo, Neil Kirby, Corinna Tannert, Oliver Rompel, Wolfgang Rascher, Matthias W. Beckmann, and Pascal Schneider. Prenatal correction of x-linked hypohidrotic ectodermal dysplasia. New England Journal of Medicine, 378:1604-1610, Apr 2018. URL: https://doi.org/10.1056/nejmoa1714322, doi:10.1056/nejmoa1714322. This article has 219 citations and is from a highest quality peer-reviewed journal.
(schneider2018prenatalcorrectionof media 9c02cda0): Holm Schneider, Florian Faschingbauer, Sonia Schuepbach-Mallepell, Iris Körber, Sigrun Wohlfart, Angela Dick, Mandy Wahlbuhl, Christine Kowalczyk-Quintas, Michele Vigolo, Neil Kirby, Corinna Tannert, Oliver Rompel, Wolfgang Rascher, Matthias W. Beckmann, and Pascal Schneider. Prenatal correction of x-linked hypohidrotic ectodermal dysplasia. New England Journal of Medicine, 378:1604-1610, Apr 2018. URL: https://doi.org/10.1056/nejmoa1714322, doi:10.1056/nejmoa1714322. This article has 219 citations and is from a highest quality peer-reviewed journal.
(rietmann2024edamissensevariant pages 1-2): Stefan J. Rietmann, Noëlle Cochet-Faivre, Helene Dropsy, Vidhya Jagannathan, Lucie Chevallier, and Tosso Leeb. Eda missense variant in a cat with x-linked hypohidrotic ectodermal dysplasia. Genes, 15:854, Jun 2024. URL: https://doi.org/10.3390/genes15070854, doi:10.3390/genes15070854. This article has 1 citations.
(rietmann2024edamissensevariant pages 2-4): Stefan J. Rietmann, Noëlle Cochet-Faivre, Helene Dropsy, Vidhya Jagannathan, Lucie Chevallier, and Tosso Leeb. Eda missense variant in a cat with x-linked hypohidrotic ectodermal dysplasia. Genes, 15:854, Jun 2024. URL: https://doi.org/10.3390/genes15070854, doi:10.3390/genes15070854. This article has 1 citations.
(schneider2018prenatalcorrectionof pages 2-3): Holm Schneider, Florian Faschingbauer, Sonia Schuepbach-Mallepell, Iris Körber, Sigrun Wohlfart, Angela Dick, Mandy Wahlbuhl, Christine Kowalczyk-Quintas, Michele Vigolo, Neil Kirby, Corinna Tannert, Oliver Rompel, Wolfgang Rascher, Matthias W. Beckmann, and Pascal Schneider. Prenatal correction of x-linked hypohidrotic ectodermal dysplasia. New England Journal of Medicine, 378:1604-1610, Apr 2018. URL: https://doi.org/10.1056/nejmoa1714322, doi:10.1056/nejmoa1714322. This article has 219 citations and is from a highest quality peer-reviewed journal.