Telangiectasia-ectodermal dysplasia-brachydactyly-cardiac anomaly (TEBC) syndrome is a rare autosomal dominant condition, recently linked to the protein kinase D1 (PRKD1) gene. The phenotype of TEBC remains incomplete at this point. Our aim is to improve the characterization of the clinical and molecular aspects of the TEBC syndrome. We report on the 8th patient carrying a heterozygous de novo variation of PRKD1 c.2134G > A, p. (Val712Met) identified by trio exome sequencing. The proband presents with partial atrioventricular septal defect, brachydactyly, ectodermal dysplasia, telangiectasia that developed in childhood, intellectual disability with microcephaly, multicystic renal dysplasia and moderate hormonal resistance. In view of this 8th description and review of the literature, it appears that neurodevelopmental disorders and microcephaly are frequently associated with PRKD1 missense variants, adding to the four main clinical signs described initially in the TEBC syndrome. Further descriptions are required to confirm the observed endocrine and kidney abnormalities. This should contribute to a more comprehensive understanding of the phenotypic spectrum and may help establish genotype-phenotype correlations. In the context of genotype-first strategy, accurate patient descriptions are fundamental. Characterization of specific syndromic associations is essential for variant interpretation support and patient follow-up, even in very rare diseases, such as the TEBC syndrome.

OBJECTIVE: To investigate the role of Keratinocyte Differentiation Factor 1 (KDF1) in ectodermal dysplasia (ED) and nonsyndromic tooth agenesis (NSTA) and perform a literature review.
METHODS: Genome sequencing was used to identify genetic variants in a Thai, NSTA proband and validated through Sanger sequencing. Pathogenicity was assessed using ACMG guidelines, MetaRNN and AlphaMissense. A comprehensive review of KDF1/NSTA cases informed genotype-phenotype analysis of the proband.
RESULTS: The proband revealed multiple missing teeth, caries and extensive periodontal disease. Deep phenotyping showed no signs of ED beyond tooth agenesis. The identified novel KDF1 variant, p.Ile243Leu, was classified as \'likely pathogenic\' by ACMG and predicted as \'detrimental\' by MetaRNN and AlphaMissense analyses. A total of 14 reviewed KDF1 cases revealed ED-associated variants (3 variants in 8 patients) clustering in the region of amino acids 251-275, within the DUF4656 domain, while NSTA-causing variants (4 variants in 6 patients) were typically found in amino- or carboxy-termini to this region. KDF1/NSTA cases exhibited an average of 15 missing teeth, with a higher prevalence in the mandible.
CONCLUSIONS: This study identifies a novel KDF1 variant-related NSTA in Thai people. The genotype-phenotype correlates suggest a distinctive pattern and tooth agenesis of KDF1-related NSTA.

Pathogenic variants in the EDARADD gene result in autosomal recessive and autosomal dominant ectodermal dysplasia. This article reports on the fourth family in the world with ectodermal dysplasia 11A (ECTD11A) cause from a novel splicing variant in the EDARADD gene, identified by whole exome sequencing and confirmed by Sanger sequencing. The proband and his mother were heterozygous for the detected variant (NM_145861.4:c.161-2A>T). The proband manifests unusual symptoms including hyperkeratotic plaques, slow-growing hair, recurrent infection, and pectus excavatum. His mother presents hypohidrosis, extensive tooth decay, fragile nails, and sparse hair. Further studies on ECTD11A patients could be useful to characterizing the phenotype features more precisely.

Pre-mRNA splicing factors are crucial in regulating transcript diversity, by removing introns from eukaryotic transcripts, an essential step in gene expression. Splicing of pre-mRNA is catalyzed by spliceosomes. CWC27 is a cyclophilin associated with spliceosome, in which genetic defects of its components have been linked to spliceosomopathies with clinical phenotypes including skeletal developmental defects, retinitis pigmentosa (RP), short stature, skeletal anomalies, and neurological disorders. We report two siblings (male and female) of Mexican descent with a novel homozygous frameshift variant in CWC27 and aim to highlight the cardinal features among the previously described 12 cases as well as expand the currently recognized phenotypic spectrum. Both siblings presented with a range of ocular and extraocular manifestations including novel features such as solitary kidney and tarsal coalition in the male sibling, together with gait abnormalities, and Hashimoto\'s thyroiditis in the female sibling. Finally, we highlight ectodermal involvement including sparse scalp hair, eyebrows and lashes, pigmentary differences, nail dysplasia, and dental anomalies as a core phenotype associated with the CWC27 spliceosomopathy.

Oligodontia is a developmental dental anomaly defined by the absence of 6 or more permanent teeth, excluding the third molars. We performed a review with a systematic approach and proposed a guideline for the choice of the bone augmentation surgery. The different bone augmentation technique terms were searched in the PubMed and Science Direct database. Clinical studies were eligible if they reported on pre-implant surgery in patients with oligodontia. The database search yielded 400 studies after duplicates removed. Thirty studies were finally included, involving 410 patients. Sixty-three sinus lifts were performed in 37 patients with no failure. Thirteen out of 33 patients with iliac bone transplantation and two out of 24 with parietal bone transplantation had resorption, one out of 4 patients who received allogeneic bone block had complete failure. Seventy-eight patients underwent guided bone regeneration, none had bone loss. No failure was found with the alveolar distraction osteogenesis technique. Four out of thirteen patients developed permanent hypoesthesia after inferior alveolar nerve transposition. The cumulative implant survival rate was 94.4% after bone augmentation procedures. Extensive edentulous areas should be grafted with parietal bone, as iliac grafts present a greater risk of resorption. Smaller edentulous areas should be treated by endobuccal harvesting or guided bone regeneration. Osteogenesis distraction and nerve transposition are effective surgeries for medium-to-large mandibular edentulous spaces. The implant survival rate is not significantly different between implants placed in grafted and nongrafted bone, the appropriate choice of bone augmentation technique can reduce the risk of peri‑implant bone resorption.

Noonan, Costello, and cardio-facio-cutaneous syndrome are neurodevelopmental disorders belonging to the RASopathies, a group of syndromes caused by alterations in the RAS/MAPK pathway. They are characterized by similar clinical features, among which feeding difficulties, growth delay, and gastro-intestinal disorders are frequent, causing pain and discomfort in patients. Hereby, we describe the main nutritional and gastrointestinal issues reported in individuals with RASopathies, specifically in Noonan syndrome, Noonan syndrome-related disorders, Costello, and cardio-facio-cutaneous syndromes. Fifty percent of children with Noonan syndrome may experience feeding difficulties that usually have a spontaneous resolution by the second year of life, especially associated to genes different than PTPN11 and SOS1. More severe manifestations often require artificial enteral nutrition in infancy are observed in Costello syndrome, mostly associated to c.34G>A substitution in the HRAS gene. In cardio-facio-cutaneous syndrome feeding issues are usually present (90-100% of cases), especially in individuals carrying variants in BRAF, MAP2K1, and MAP2K2 genes, and artificial enteral intervention, even after scholar age, may be required. Moreover, disorders associated with gastrointestinal dysmotility as gastro-esophageal reflux and constipation are commonly reported in all the above-mentioned syndromes. Given the impact on growth and on the quality of life of these patients, early evaluation and prompt personalized management plans are fundamental.

The Adams-Oliver syndrome is a rare congenital disorder characterized by aplasia cutis congenita of the scalp, terminal transverse limb defects, and congenital telangiectatic cutis marmorata. It can occur through different inheritance patterns: autosomal dominant, autosomal recessive, or de novo dominant mutations. Although the Adams-Oliver syndrome is a rare disease, it is essential to know its clinical characteristics and inheritance patterns, to establish a correct diagnosis and its possible complications during follow-up. In the present study, we describe the case of an adolescent with Adams-Oliver syndrome with an autosomal dominant inheritance pattern, pulmonary hypertension and plastic bronchitis, and several compromised family members.
El síndrome de Adams-Oliver es un trastorno congénito raro, caracterizado por aplasia cutis congénita en el cuero cabelludo, defectos terminales transversales de las extremidades y piel marmorata telangiectásica congénita. Este puede presentarse debido a diferentes patrones de herencia de tipo autosómico dominante o autosómico recesivo, o por mutaciones dominantes de novo. Aunque el síndrome de Adams-Oliver es una enfermedad poco frecuente, es importante conocer sus características clínicas y patrones de herencia, para así establecer un correcto diagnóstico y sus posibles complicaciones durante el seguimiento. En el presente estudio, se describe el caso de una adolescente con síndrome de Adams-Oliver con patrón de herencia autosómica dominante, hipertensión pulmonar y bronquitis plástica. Había varios miembros de su familia con el mismo compromiso.

Congenital heart defect (CHD) is a birth defect that affects the structure of the heart. Although CHD is often multifactorial, it can also be inherited as part of a Mendelian disorder such as in congenital heart defect and ectodermal dysplasia (CHDED). This disorder is caused by de novo variants in PRKD1. Here, we describe a patient with a novel de novo variant of PRKD1 with phenotypic features consistent with CHDED. Previously unreported features were noted including high intracranial pressure (ICP), partial anomalous pulmonary venous return (PAPVR), and bifid uvula. We suggest that these features may be associated with CHDED.

The objective of this systematic review was to determine the orthodontic and dentofacial orthopedic treatments carried out in patients with ectodermal dysplasia to facilitate functional and aesthetic rehabilitation.
The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. We systematically searched PubMed, Web of Science, Scopus, Scielo, LILACS, EBSCOhost and Embase databases up to 6 January 2022. We included articles describing patients with any type of ectodermal dysplasia who received orthodontic or dentofacial orthopedic treatment to facilitate functional and aesthetic oral rehabilitation. The search was not restricted by language or year of publication. The quality of the studies was assessed using the Joanna Briggs Institute Quality Assessment Scale of the University of Adelaide for case series and case reports. The review was registered at the University of York Centre for reviews (CRD42021288030).
Of the initial 403 studies found, 29 met the inclusion criteria. After applying the quality scale, 23 were left for review-21 case reports and 2 case series. The initial age of patients ranged from 34 months to 24 years. Thirteen studies were on hypohidrotic and/or anhidrotic ectodermal dysplasia, of which two were X-chromosome linked. In one study, the patient had Wiktop syndrome, and in nine the type of ectodermal dysplasia was not specified. The duration of treatment was 7 weeks to 10 years. The treatments described were: fixed orthodontic appliances or simple acrylic plates designed for tooth movement, including leveling and aligning, closing of diastemata, retraction of impacted teeth in the dental arch; clear aligners; fixed and/or removable appliances for the correction of skeletal and/or dentoalveolar relationships; palatal expanders in combination with face masks for orthopedic traction of the maxilla; and orthognathic surgery. Only three studies provided cephalometric data.
The level of evidence of the articles reviewed was low and most orthopedic and dentofacial orthodontic treatments described were focused on correcting dental malpositioning and jaw asymmetries and not on stimulating growth from an early age. Studies with greater scientific evidence are needed to determine the best treatment for these patients.

OBJECTIVE: EEC is a rare syndrome characterized by the triad of ectrodactyly, ectodermal dysplasia, and orofacial clefting, along with other clinical manifestations mainly in hair, skin, and teeth. The present paper aimed to perform a scoping review to collect the most relevant studies and focused on the diagnosis and oral management of EEC syndrome in the pediatric dental setting. This review also pretended to make recommendations and map the gaps in this clinical topic.
METHODS: An exhaustive electronic and manual search was conducted in four databases (PubMed, EMBASE, Google Scholar, and Dentistry & Oral Sciences Source/EBSCO) according to previously established eligibility criteria, using different combinations of keywords, MeSH terms, and Boolean operators. Titles, abstracts, and full-text articles were screened and selected by precalibrated reviewers. A data charting was also accomplished for summarizing the overview of the evidence.
RESULTS: A total of 37 references were identified, and 32 titles remained after removing duplicates; then, 25 potential full-text articles were carefully reviewed. Finally, 15 relevant and most informative studies were included. Most studies were single clinical case reports. Only one descriptive retrospective study was detected. None randomized clinical trials or comparative observational studies were found. A medical/dental multidisciplinary approach is needed for the management of EEC syndrome.
CONCLUSIONS: Diverse dental specialists must be involved. Pediatric dentists must play a principal role in the prevention and treatment of oral diseases; particularly the preservation of the primary and mixed dentitions, trying to achieve normal orofacial growth.