A four-year-old boy with X-linked hypohidrotic ectodermal dysplasia (XLHED) presented with complete anodontia, severe esthetic concerns, and functional limitations. The treatment plan aimed to provide both functional restoration and esthetic improvement, utilizing a fully digital workflow. After a comprehensive clinical and radiographic evaluation, digital cast scanning and 3D analysis were used to create a precise virtual plan for the fabrication of a customized complete denture. The initial dentures were followed by regular follow-up visits at 6-month intervals, with the patient returning for adjustments to accommodate his rapid growth. Over a five-year period of follow-up, the child received updated dentures as his facial and oral structures developed. This approach not only restored the boy's masticatory, speech, and esthetic functions but also allowed for continuous adaptation of the prostheses as the child grew. This report contributes to the existing literature by introducing a reproducible, quantitative workflow. Unlike purely descriptive digital denture reports, this protocol integrates a quantitative segmented morphometric analysis into a fully digital workflow to support objective, growth‑oriented clinical decision‑making, particularly in distinguishing between conservative relining and the need for complete prosthesis refabrication.

Ectodermal dysplasia (ED) is characterized by sparse hair, reduced sweat gland secretion, and congenital absence of teeth. While genes such as EDA and EDAR have been identified as causative factors of ED, the underlying mechanisms remain unknown, and corresponding treatments are not available. Here, we report a pedigree with hypohidrotic ectodermal dysplasia (HED), the most common subtype of ED, caused by a mutation in the KDF1 gene. To investigate disease mechanisms, we generated induced pluripotent stem cells (iPSCs) of family members. Upon differentiation into embryoid bodies (EBs), the KDF1 mutation severely impaired EB size and morphology. The single-cell RNA sequencing further demonstrated that iPSCs from both HED patients showed a specific shortage of several cell populations, whose biological characteristics were closely related to synapse structure and signaling. Initially, iPSCs were differentiated into neurons to analyze their functional changes. Concurrently, patient-derived iPSCs were differentiated into epidermal progenitor cells, and the effect of the N-methyl-D-aspartate receptor antagonist MK-801 during this process was investigated. We found that the overexpression of excitatory neurotransmitters might disrupt ectodermal development. These deficits were partially rescued after CRISPR-mediated correction of the KDF1 mutation. Our work suggests that impaired synaptic structure and signaling impede ectodermal organogenesis in HED.

Digital oral rehabilitation for children with hypohidrotic ectodermal dysplasia

ABSTRACT Hypohidrotic ectodermal dysplasia (HED) is a rare congenital disorder characterized by abnormal development of ectodermal structures including hair, teeth, nails, and sweat glands. Dental manifestations such as anodontia or hypodontia can significantly impair mastication, speech development, facial esthetics, and psychosocial well‐being, particularly in young children. This case report describes the early oral rehabilitation of a 6 year old male child from Kabul, Afghanistan, clinically diagnosed with HED and presenting with oligodontia, heat intolerance, and characteristic craniofacial features. Clinical and radiographic evaluation confirmed the absence of multiple primary and developing permanent teeth. Considering the patient's young age, ongoing craniofacial growth, underdeveloped alveolar ridges, and limited socioeconomic resources, removable complete dentures were fabricated as an interim prosthetic solution using functional impression techniques. Following prosthetic rehabilitation, the child demonstrated notable improvement in masticatory function, speech clarity, facial appearance, and self‐confidence during follow‐up. This case highlights the importance of early, growth‐adapted, and cost‐effective prosthetic management in pediatric patients with HED, particularly in resource‐limited settings.

Hypohidrotic ectodermal dysplasia (HED), caused by mutations in genes such as EDAR, is a genetic disorder characterized by hypodontia, hypotrichosis, and hypohidrosis. Dental anomalies in HED patients lead to functional and aesthetic impairments, necessitating multidisciplinary interventions. This case report highlights the role of combined orthodontic and prosthodontic approaches in managing HED-related dental deficiencies. This clinical report describes the multistage treatment of a 32-year-old woman diagnosed with a dominant case of ED with c.175-2(IVS 3)A > G mutation of the EDAR gene based on the patient’s specific clinical manifestations and genetic profile. The patient went for orthodontic treatment due to hypodontia and lack of vertical space. Afterward, implants and crowns were placed following a computer-guided protocol. The patient was satisfied with the results of the treatment in terms of functionality and aesthetics. Multidisciplinary dental rehabilitation effectively addresses functional and aesthetic challenges in HED patients. Early diagnosis, genetic testing, and tailored orthodontic-prosthodontic strategies are critical for optimizing outcomes. Clinicians should consider genetic etiologies in patients presenting with hypodontia and ectodermal abnormalities.

To evaluate the effectiveness of autologous free parietal periosteum combined with cranial vault bone autografts for alveolar ridge reconstruction in patients with ectodermal dysplasia. Prospective single-center study; 17 patients aged 17-40 years. Two groups were formed by membrane type: autologous free periosteum (n=6) and collagen membrane (n=11). Bone augmentation was performed with fixation of parietal bone autografts; the spaces between blocks were filled with a mixture of autogenous bone chips and xenograft (70:30). Changes in bone volume were calculated relative to the total volume of the maxilla and mandible using manual slice-by-slice segmentation of MSCT scans with MPR correction (Amira 5.4.5) preoperatively, at 2-3 days, and at 6 months. Graft resorption was assessed at 6 months. Dental implant stability was measured immediately after placement and at 6 months. Statistical processing was performed in IBM SPSS. Both groups demonstrated an increase in bone volume that persisted at 6 months; no between-group differences in volume were found. Graft resorption was lower with autologous free periosteum than with a collagen membrane: maxilla 18.48±1.27% vs 23.56±4.83% (p=0.025); mandible 26.22±1.74% vs 38.68±4.68% (p<0.001). Six-month implant stability was higher in the periosteum group (ISQ 86.83±2.04 vs 82.45±1.69; p<0.001). No complications of bone grafting or dental implantation were recorded. Using autologous free parietal periosteum as a barrier membrane in cranial vault autograft reconstruction provides better graft volume preservation, lower resorption, and higher dental implant stability compared with a collagen membrane.

Hypohidrotic ectodermal dysplasia (HED) encompasses a group of rare genetic disorders affecting two or more ectodermal derivatives (hair, teeth, nails, certain glands). The condition can be inherited in an X-linked, autosomal dominant, or autosomal recessive manner, with the majority of cases caused by mutations in the EDA, EDAR, EDARADD, and WNT10A genes. This study aimed to evaluate the distribution of pathogenic and likely pathogenic variants in 261 unrelated families affected by HED in the Russian Federation (comprising 455 patients in total) between 2007 and 2024. To achieve this objective, we employed Sanger sequencing, targeted gene panel sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and segregation analysis to clarify the pathogenicity of variants of uncertain significance. A total of 261 unrelated probands, comprising 196 males (75.1%) and 65 females (24.9%), were included. Pathogenic or likely pathogenic variants were identified in 183 probands (70.1%). The distribution of mutated genes was as follows: EDA (n = 155, 84.7%), WNT10A (n = 16, 8.8%), and EDAR (n = 12, 6.5%). No apparent pathogenic mutations were detected in EDARADD. Additionally, we report 46 novel causative variants for HED, along with recurrent mutations in the EDA, WNT10A, and EDAR genes. We also identified that 28.8% of all causative variants in EDA are de novo. This is the only molecular study conducted in the Russian population affected by HED and represents the largest HED cohort published to date globally. Our findings significantly expand the mutational spectrum of HED-causing genes and will aid in choosing an initial diagnostic approach for HED patients. Further studies using whole-genome sequencing (WGS) will help to identify other contributory genes in the remaining uncharacterized Russian patients with HED.

Germline monoallelic gain-of-function (GOF) variants in NFKBIA, encoding IκBα, cause a rare immunodeficiency syndrome classically described as autosomal-dominant anhidrotic ectodermal dysplasia with immunodeficiency. However, the pathogenic spectrum of variants within the N-terminal hotspot and the extent to which distinct alleles converge on shared immunologic phenotypes are not fully defined. We studied four unrelated patients with de novo heterozygous NFKBIA variants (p.G33D, p.M37R, p.M37K, p.D31H), including two novel alleles (p.G33D and p.D31H). Clinical and immunological phenotyping, T-cell and B-cell subset analysis, and CFSE-based lymphocyte proliferation assays were performed. Functional consequences were assessed by TNF-α-induced IκBα degradation in patient PBMCs and by NF-κB dual-luciferase reporter assays in HEK293T cells expressing wild-type or mutant IκBα. A comprehensive literature review of all previously reported NFKBIA GOF cases was performed. Clinical severity ranged from recurrent sinopulmonary infections onset in adolescence to severe infantile multisystem disease with bacterial, fungal, and opportunistic infections. All patients exhibited ectodermal abnormalities, and one had autoantibodies. Despite marked clinical heterogeneity, all four patients showed a qualitatively convergent lymphocyte phenotype characterized by expanded naïve T-cell and B-cell compartments and reduced memory and effector subsets. PHA-induced CD4+ and CD8+ T-cell proliferation was preserved in P1 and P3, whereas anti-CD3/CD28-induced T-cell proliferation, assessed only in P3, was impaired, while B-cell proliferation was preserved in the tested patients. Patient PBMCs exhibited markedly delayed or minimal TNF-α-induced IκBα degradation, and all four mutant proteins more strongly suppressed TNF-α-induced NF-κB reporter activity compared to wild-type IκBα. Baseline expression of the IκBα-EGFP fusion proteins was comparable across wild-type and all four mutant constructs. These findings broaden the clinical and genotypic spectrum of N-terminal IκBα GOF disease, identify a consistent immune phenotype characterized by expanded naïve and contracted memory lymphocyte compartments, and support defective regulated IκBα degradation and impaired lymphocyte maturation as shared features of N-terminal IκBα GOF disease.

Conical Incisors as the First Manifestation of Hypohidrotic Ectodermal Dysplasia.

Introduction Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) is an X-linked inborn error of immunity caused by hypomorphic mutations in the IKBKG gene, disrupting NF-κB signaling. Its clinical presentation is heterogeneous and includes severe bacterial, mycobacterial, viral, and fungal infections, along with classic ectodermal features such as hypohidrosis, hypotrichosis, and hypodontia. Case Presentation We report a 1-year-4-month-old Peruvian male with recurrent severe infections since the first month of life, including oral candidiasis, complicated pneumonia, central nervous system tuberculous granuloma, sepsis, and cytomegalovirus viremia. Physical examination revealed facial dysmorphism, sparse hair, xerosis, hypohidrosis, and conical teeth. Immunological evaluation showed hypogammaglobulinemia (IgG 435 mg/dL) with normal IgA and IgM levels, and unremarkable T, B, and natural killer cell subsets. Monthly intravenous immunoglobulin therapy and antimicrobial prophylaxis were initiated. A primary immunodeficiency gene panel revealed only variants of uncertain significance (VUS), and exome sequencing failed to identify a candidate gene. Ultimately, targeted Sanger sequencing identified a VUS in IKBKG [c.522_527dup; p.R175_A176dup], located in a functionally critical region of the NEMO protein. Discussion The clinical phenotype and genetic findings support a presumptive diagnosis of EDA-ID. The localization of the VUS suggests a potential structural disruption, impairing IKK complex oligomerization and NF-κB activation, affecting both innate and adaptive immunity. This may represent the first clinically well-documented suspected case of EDA-ID in Peru and South America. The case underscores the importance of early clinical recognition and stepwise molecular diagnostics in immunodeficiencies and highlights the regional need for functional and familial studies to confirm the pathogenicity of IKBKG variants and improve diagnosis.

Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that can caused by mutations in the EDAR gene, which encodes the Ectodysplasin A receptor, leading to defective ectodermal structure development. This study investigates the molecular impact of a novel homozygous c.730 + 1G > T splice site variant in the EDAR gene, identified in a consanguineous Iranian family with HED. The 10-year-old proband presented with a classic, severe HED phenotype, including anhidrosis (impaired sweating) leading to recurrent hyperthermia, sparse hair, dry skin, and severe oligodontia with only three teeth present. Co-occurring thyroid dysfunction was also noted. To elucidate the variant’s predicted structural and functional consequences (likely exon 8 skipping), Molecular Dynamics (MD) simulations were performed over 50 ns, focusing on the EDAR protein’s conformational dynamics. The simulations revealed that the predicted variant-induced structural alteration leads to a more compact and rigid EDAR structure, significantly reducing its conformational flexibility. This structural change likely disrupts critical receptor interactions and downstream signaling, which are key factors in HED pathogenesis. These findings highlight the power of combining detailed clinical phenotyping with MD simulations in uncovering the precise molecular mechanisms underlying EDAR dysfunction in HED, expanding the mutational spectrum of the gene and supporting precise genetic diagnosis for improved clinical management.

Clouston syndrome or hypohidrotic ectodermal dysplasia is a rare autosomal dominant disorder caused by a mutation in the GJB6 gene. Its main clinical features include the triad of palmoplantar keratoderma, nail dystrophy, and hypotrichosis. A pediatric patient with nail and hair abnormalities was diagnosed clinically and genetically with this condition, and a diagnostic algorithm for approaching causes of pachyonychia in pediatric patients is presented. The importance of genetic counselling and appropriate differential diagnosis underscore the need for early clinical suspicion to initiate suitable therapeutic and supportive interventions.

Prosthetic and implant rehabilitation in hypohidrotic ectodermal dysplasia: A 13-year follow-up.

Our clinical findings, together with the identification of novel variants in EDAR, LIPH, LPAR6, HR, and TP63, expand the clinical and molecular spectrum of ectodermal dysplasias. A potential association between microcephaly and ectodermal dysplasia is discussed. This study highlights the genetic heterogeneity of ectodermal dysplasias and emphasizes the importance of combining detailed clinical evaluation with molecular diagnostics. • Ectodermal dysplasias (EDs) are congenital disorders characterized by abnormal development of at least two of four ectodermal structures, such as hair, nails, teeth, and sweat glands. EDs represent a clinically and genetically heterogeneous group of disorders with over 200 distinct types described. • In the current study, we report the clinical and molecular genetic analysis of 36 patients and contribute to the genotype-phenotype correlation. Five novel variants were identified. Microcephaly was observed in 47% of patients in the hypohidrotic ectodermal dysplasia group and in 66% of patients carrying CDH3 variants. The patient with a TSPEAR variant also had Beckwith-Wiedemann syndrome.

Hypohidrotic ectodermal dysplasia (HED) is the most common form of ectodermal dysplasia in the general population. The clinical manifestations of HED include fever due to hypohidrosis, hypotrichosis, dental hypoplasia, and characteristic aged facial features, along with multisystem involvement. Over 20 genes have been implicated in HED, with EDA being the most frequent pathogenic gene. To expand the mutational spectrum of HED and explore the association between EDA mutations and hypotrichosis. Whole-exome sequencing, target gene sequencing, and Sanger sequencing were performed with prediction of protein structure. We identified five novel variants and five structural variants (with large indels and copy number variation). Copy number variation was validated through targeted sequencing and quantitative PCR. Patients harbouring deletion, nonsense, and splice-site mutations exhibited more severe phenotypes. We report a series of HED cases with mutations in EDA, EDAR, and NFKBIA, expanding the mutational spectrum of EDA, with analysis of genotype-phenotype correlations associated with EDA mutations. We propose that focal alopecia may serve as an easily observable clinical marker for disease severity stratification. Mutations disrupting critical structural domains or altering spatial conformation of the EDA protein may underlie these severe clinical manifestations by impairing protein stability or functional interactions.

Ectrodactyly–ectodermal dysplasia–clefting syndrome is a rare autosomal dominant disorder with variable expression and penetrance and involves both ectodermal and mesodermal tissues. Here, we report the case of a 28-year-old female presenting with bilateral severe dry eye and features suggestive of ectrodactyly and hypohidrotic ectodermal dysplasia. She had lobster claw deformities, severe dry skin, and ocular features such as madarosis, ankyloblepharon, conjunctival xerosis, and corneal scarring. A combined effort involving ophthalmologist, dermatologist, and dentist is required to successfully manage these patients.

Focal dermal hypoplasia with clinical features mimicking classic hypohidrotic ectodermal dysplasia and cardiofaciocutaneous syndrome.

The purpose of this report is to describe a seven year-old boy diagnosed with hypohidrotic ectodermal dysplasia who was rehabilitated with dental implants and partial removal prosthesis. The patient had only three dental elements: primary maxillary right first molar and primary maxillary right and left canines. The patient underwent treatment under general anesthesia in a hospital setting. Two dental implants were placed in the mandibular arch to support a dental prosthesis. Due to the COVID-19 pandemic, there was a prolonged period before continuing with the rehabilitative phase. Upon resumption, peri-implant mucositis was observed. Through professional and home plaque control measures, peri-implant tissue health was restored. A removable prosthesis was fabricated for the maxillary arch and O-ring attachments were used for the mandibular prosthesis. Given the patient's growth, prostheses may need to be replaced approximately every six months until growth is complete.

A case of orthognathic surgery for jaw deformity with hypohidrotic ectodermal dysplasia

Background: Anhidrotic ectodermal dysplasia (AED), also referred to as hypohidrotic ectodermal dysplasia, is a rare genetic condition characterized by a triad of hypotrichosis, hypodontia, and hypohidrosis. Case Report: This article reports two illustrative cases: an adolescent and a child, both presenting with classic AED manifestations. Discussion: We describe the clinical and histological features, provide insights into the diagnostic process, and discuss recent advances in the understanding and management of AED. Conclusion: AED is a rare genetic disorder that requires early diagnosis, regular follow-up, and genetic counseling. New therapies offer promising outcomes.