Surgical and prosthetic rehabilitation of siblings with Witkop tooth and nail syndrome using zygomatic implants: a familial case series of 3 patients with up to 15-year follow-up.

Witkop tooth and nail syndrome is a rare, autosomal dominant type of ectodermal dysplasia that can have significant effects on dentition, including hypoplastic and malformed dentition and significantly atrophic maxillas. Endosseous implants have become one possible solution to replace missing teeth, although their use in areas where bone is sparse becomes challenging. Due to the severe atrophy of the maxillary alveolus, extensive preprosthetic surgeries including orthognathic surgery, extensive bone grafting, and sinus floor augmentations have been recommended prior to placement of endosseous dental implants. Although this treatment has shown favorable outcomes, it requires multiple surgical procedures, contributing to a prolonged treatment course and increased morbidity. An alternative treatment of atrophic maxillas in patients with ectodermal dysplasia includes the use of zygomatic implants. This familial case series discusses 3 siblings, all previously diagnosed with Witkop Syndrome, who underwent comprehensive preprosthetic surgery and prosthetic rehabilitation using zygomatic implants with a follow-up period up to 15 years.

Gene Mutations of the Three Ectodysplasin Pathway Key Players (EDA, EDAR, and EDARADD) Account for More than 60% of Egyptian Ectodermal Dysplasia: A Report of Seven Novel Mutations.

Ectodermal dysplasia (ED) is a diverse group of genetic disorders caused by congenital defects of two or more ectodermal-derived body structures, namely, hair, teeth, nails, and some glands, e.g., sweat glands. Molecular pathogenesis of ED involves mutations of genes encoding key proteins of major developmental pathways, including ectodysplasin (EDA) and wingless-type (WNT) pathways. The most common ED phenotype is hypohidrotic/anhidrotic ectodermal dysplasia (HED) featuring hypotrichosis, hypohidrosis/anhidrosis, and hypodontia. Molecular diagnosis is fundamental for disease management and emerging treatments. We used targeted next generation sequencing to study EDA, EDAR, EDARADD, and WNT10A genes in 45 Egyptian ED patients with or without hypohidrosis. We present genotype and phenotype data of 28 molecularly-characterized patients demonstrating genetic heterogeneity, variable expressivity, and intrafamilial phenotypic variability. Thirteen mutations were reported, including four novel EDA mutations, two novel EDARADD, and one novel EDAR mutations. Identified mutations congregated in exons encoding key functional domains. EDA is the most common gene contributing to 85% of the identified Egyptian ED genetic spectrum, followed by EDARADD (10%) and EDAR (5%). Our cohort represents the first and largest cohort from North Africa where more than 60% of ED patients were identified emphasizing the need for exome sequencing to explore unidentified cases.

Membranous aplasia cutis congenita in trisomy 18.

BACKGROUND: Aplasia cutis congenita (ACC) is a rare congenital condition characterized by the absence of skin layers and sometimes other underlying structures, in a localized or widespread area. The exact etiopathogenesis is not yet completely understood. Membranous ACC (MACC) also described as bullous or cystic ACC is a clinical subtype of ACC, covered with a membranous or glistening surface, and appears as a flat scar. There are less than 20 cases reported in the literature. It has been proposed an abortive form of a defective closure of the neural tube. On the other hand, the trisomy 18 is a chromosomal abnormality characterized by a broad clinical spectrum and the presence of defective closure of the neural tube. CASE PRESENTATION: We report on an 18-months-old Venezuelan boy, who presented on the parietal scalp a distinctive localized MACC appearing as an oval lesion covered with a membranous surface, characterized by the absence of hairs and the presence of a sharp hair collar. The karyotype in peripheral blood was 47,XY,+ 18. CONCLUSIONS: This is the second case report of ACC in trisomy 18 and reinforces the interpretation of a non-fortuitous association as well as of a defective closure of the neural tube as pathogenetic mechanism. The case highlights the importance of examining for dermatological alterations such as ACC in cases of chromosomopathy.

Ectodermal Dysplasia: Association with Anti-Basement Membrane Autoantibodies.

Ectodermal dysplasia (ED) is a group of several genetic conditions with absence or dysgenesis of at least two ectodermal derivatives: teeth, skin and its appendages including hair, nails, eccrine and sebaceous glands. The most important clinical findings in patients with ED are hypodontia, hypotrichosis, and hypohidrosis, which can lead to episodes of hyperthermia. Few reports have focused on the progressive keratopathy in ED. Cicatrizing conjunctivitis associated with anti-basement membrane autoantibodies has been described. We report a series of three ectodermal dysplasia patients with an ocular phenotype typically seen in ocular mucous membrane pemphigoid; conjunctival immunohistopathology revealed anti-basement membrane autoantibodies in all of them, and systemic immunosuppression proved to be effective in improving symptoms and helping to stabilize ocular surface disease.

Expanding the phenotype in Adams-Oliver syndrome correlating with the genotype.

RATIONALE: Adams-Oliver syndrome (AOS) is a genetic disorder characterized by the association of aplasia cutis congenita (ACC), terminal transverse limb defect (TTLD), congenital cardiac malformation (CCM), and minor features, such as cutaneous, neurological, and hepatic abnormalities (HAs). The aim of the study is to emphasize phenotype-genotype correlations in AOS. METHODS: We studied 29 AOS patients. We recorded retrospectively detailed phenotype data, including clinical examination, biological analyses, and imaging. The molecular analysis was performed through whole exome sequencing (WES). RESULTS: Twenty-nine patients (100%) presented with ACC, the principal inclusion criteria in the study. Seventeen of twenty-one (81%) had cutis marmorata telangiectasia congenita, 16/26 (62%) had TTLD, 14/23 (61%) had CCM, 7/20 (35%) had HAs, and 9/27 (33%) had neurological findings. WES was performed in 25 patients. Fourteen of twenty-five (56%) had alterations in the genes already described in AOS. CCM and HAs are particularly associated with the NOTCH1 genotype. TTLD is present in patients with DOCK6 and EOGT alterations. Neurological findings of variable degree were associated sometimes with DOCK6 and NOTCH1 rarely with EOGT. CONCLUSION: AOS is characterized by a clinical and molecular variability. It appears that degrees of genotype-phenotype correlations exist for patients with identified pathogenic mutations, underlining the need to undertake a systematic but adjusted multidisciplinary assessment.

Displasia ectodérmica hipohidrótica autosómica dominante asociada a hipoparatiroidismo / Autosomal dominant hypohidrotic ectodermal dysplasia associated to hypoparathyroidism

RESUMEN Las displasias ectodérmicas constituyen alteraciones de los derivados embriológicos del ectodermo. Paciente adulta, con hipoparatiroidismo, llamó la atención por su fenotipo y fue remitida de la consulta de Neurología a la consulta Genética. Se diagnosticó una displasia ectodérmica hipohidrótica, de origen genético con herencia autosómica dominante, poco común para esta entidad. Se presenta este caso con el objetivo de describir las manifestaciones clínicas de esta alteración genética, las cuales nunca fueron objeto de interés médico resultando inadvertidas para su estudio y diagnóstico. Esta alteración se asocia a una condición patológica como el hipoparatiroidismo, en la literatura revisada no se encontraron reportes de la misma. La evaluación clínica de la paciente permitió hacer el diagnóstico y explicar muchos de los problemas para los cuales no existían respuestas, así como ofrecer un asesoramiento genético adecuado para ella y para sus familiares con riesgo de padecer una condición genética similar (AU).

ABSTRACT Ectodermic dysplasias are alterations of the ectoderm embryologic derivatives. This is a case of an adult female patient with hypoparathyroidism, drawing attention due to her phenotype; she was remitted by the consultation of Neurology to the Genetic one. She was diagnosed a hypohidrotic ectodermal dysplasia, of genetic origin with autosomal dominant inheritance, what is very rare for this entity. The case is presented with the aim of describing the clinical manifestation of this genetic alteration that never drew medical interest and nobody diagnosed or studied. It is associated to a pathologic condition like hypothyroidism and was not reported in medical literature before. The clinical evaluation of the patient allowed arriving to the diagnostic and explaining many problems that were unexplained, and also offering the adequate genetic advice to her and her relatives likewise at risk of suffering a similar genetic condition (AU).

Displasia ectodérmica hipohidrótica autosómica dominante asociada a hipoparatiroidismo / Autosomal dominant hypohidrotic ectodermal dysplasia associated to hypoparathyroidism

RESUMEN Las displasias ectodérmicas constituyen alteraciones de los derivados embriológicos del ectodermo. Paciente adulta, con hipoparatiroidismo, llamó la atención por su fenotipo y fue remitida de la consulta de Neurología a la consulta Genética. Se diagnosticó una displasia ectodérmica hipohidrótica, de origen genético con herencia autosómica dominante, poco común para esta entidad. Se presenta este caso con el objetivo de describir las manifestaciones clínicas de esta alteración genética, las cuales nunca fueron objeto de interés médico resultando inadvertidas para su estudio y diagnóstico. Esta alteración se asocia a una condición patológica como el hipoparatiroidismo, en la literatura revisada no se encontraron reportes de la misma. La evaluación clínica de la paciente permitió hacer el diagnóstico y explicar muchos de los problemas para los cuales no existían respuestas, así como ofrecer un asesoramiento genético adecuado para ella y para sus familiares con riesgo de padecer una condición genética similar.

ABSTRACT Ectodermic dysplasias are alterations of the ectoderm embryologic derivatives. This is a case of an adult female patient with hypoparathyroidism, drawing attention due to her phenotype; she was remitted by the consultation of Neurology to the Genetic one. She was diagnosed a hypohidrotic ectodermal dysplasia, of genetic origin with autosomal dominant inheritance, what is very rare for this entity. The case is presented with the aim of describing the clinical manifestation of this genetic alteration that never drew medical interest and nobody diagnosed or studied. It is associated to a pathologic condition like hypothyroidism and was not reported in medical literature before. The clinical evaluation of the patient allowed arriving to the diagnostic and explaining many problems that were unexplained, and also offering the adequate genetic advice to her and her relatives likewise at risk of suffering a similar genetic condition.

Pain in individuals with RASopathies: Prevalence and clinical characterization in a sample of 80 affected patients.

Pain in individuals with RASopathies is a neglected topic in literature. In this article, we assessed prevalence and profile of pain in a sample of 80 individuals affected by RASopathies. The study sample included individuals with Noonan syndrome (N = 42), Costello syndrome (N = 17), and cardio-facio-cutaneous syndrome (N = 21). A set of standardized questionnaires and scales were administered (VAS/numeric scale, r-FLACC, Wang-Baker scale, NPSI, BPI, NCCPC-R) to detect and characterize acute and chronic pain and to study the influence of pain on quality of life (PEDs-QL, SF-36) and sleeping patterns (SDSC); revision of past medical history and multisystemic evaluation was provided. Available clinical data were correlated to the presence of pain. High prevalence of acute (44%) and chronic (61%) pain was documented in the examined sample. Due to age and intellectual disability, acute pain was localized in 18/35 individuals and chronic pain in 33/49. Muscle-skeletal and abdominal pain was more frequently reported. The intensity of acute and chronic pain interfered with daily activities in 1/3 of the sample. Pain negatively impacted on QoL and sleeping patterns. This work documents that pain is highly prevalent in RASopathies. Future studies including subjective and objective measures of pain are required to discriminate a somatosensory abnormality from an abnormal elaboration of painful stimuli at a central level.

Etiología, manifestaciones clínicas y estudio por imágenes de la displasia ectodérmica: Una revisión de la literatura / Etiology, clinical manifestations and study by images of ectodermal dysplasia: a literature review

La displasia ectodérmica (DE) es un trastorno hereditario multisistémico que involucra dos o más de las estructuras ectodérmicas, que incluyen alteraciones en la piel, cabello, uñas, dientes y glándulas sudoríparas. Las manifestaciones bucales más frecuentes son alteraciones dentarias en número y forma, como anodoncias e hipodoncias en ambas denticiones, gérmenes dentarios distróficos, dientes impactados, en forma de clavija, conoides, microdoncia, diastemas, etc. El diagnóstico clínico siempre va acompañado de estudios imagenológicos y, según la edad en que se diagnostique, el tratamiento siempre estará dirigido a restablecer y mejorar la calidad de vida. El objetivo de este trabajo es revisar la etiología, las manifestaciones clínicas y las características imagenológicas observadas en radiografías panorámicas, laterales de cráneo, cefalometrías y tomografías computarizadas de haz cónico (TCHC), con la finalidad de contribuir y ser parte del manejo multidisciplinario para lograr diagnósticos y tratamientos seguros y confiables. (AU)

Ectodermal dysplasia (ED) is a multi-systemic hereditary disorder, involving two or more of the ectodermal structures, which includes alterations in the skin, hair, nails, teeth and sweat glands.The most frequent oral manifestations are dental alterations in number and form such as: anodontias and hypodontias in both primary and permanent dentitions, dystrophic tooth buds, impacted, peg-shaped, conoid teeth, microdontia, dias-tema, etc. Clinical diagnosis is always accompanied by imaging studies and depending on the age at time of diag-nosis, treatment is aimed at restoring and improving quality of life.The objective of this study is to review the etiology, clinical manifestations and imaging characteristics observed in panoramic and lateral skull radio-graphs, cephalometry and cone beam computed tomography (CBCT), in order to contribute to multidisciplinary manage-ment, diagnoses, and safe and reliable treatments. (AU)

Etiología, manifestaciones clínicas y estudio por imágenes de la displasia ectodérmica: Una revisión de la literatura / Etiology, clinical manifestations and study by images of ectodermal dysplasia: a literature review

La displasia ectodérmica (DE) es un trastorno hereditario multisistémico que involucra dos o más de las estructuras ectodérmicas, que incluyen alteraciones en la piel, cabello, uñas, dientes y glándulas sudoríparas. Las manifestaciones bucales más frecuentes son alteraciones dentarias en número y forma, como anodoncias e hipodoncias en ambas denticiones, gérmenes dentarios distróficos, dientes impactados, en forma de clavija, conoides, microdoncia, diastemas, etc. El diagnóstico clínico siempre va acompañado de estudios imagenológicos y, según la edad en que se diagnostique, el tratamiento siempre estará dirigido a restablecer y mejorar la calidad de vida. El objetivo de este trabajo es revisar la etiología, las manifestaciones clínicas y las características imagenológicas observadas en radiografías panorámicas, laterales de cráneo, cefalometrías y tomografías computarizadas de haz cónico (TCHC), con la finalidad de contribuir y ser parte del manejo multidisciplinario para lograr diagnósticos y tratamientos seguros y confiables. (AU)

Cinco casos de aplasia cutis congénita / Five cases of aplasia cutis congénita

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[Newborn with aplasia cutis caused by epidermolysis bullosa].

Epidermiolysis bullosa (EB) is a rare group of genetic disorders, which are characterised by bullae and erosions on skin and mucosa. This case report describes a patient, who was born at full term without any complications. Both crurae were affected by aplasia cutis. Upon birth, the newborn was wrapped in a soft blanket, and prophylactic antibiotic treatment was started along with analgesics. Large bullae were punctured with a sterile needle, and erosions were treated with non-adherent wound dressings and special bandages. Gloves and shoes were custom-made. Autosomal recessive dystrophic EB was genetically confirmed, and the child was followed regularly by an EB-team.

A practical approach to the evaluation and treatment of an infant with aplasia cutis congenita.

Aplasia cutis congenita (ACC) is a term describing absence of skin at birth. ACC is a rare cutaneous finding, often noted with no other physical abnormalities. The etiology of ACC varies, and there are likely several causes for its development. ACC can be located anywhere on the body. Its clinical appearance and location can alert the clinician to other potential abnormalities and associations. This discussion covers the diagnosis of ACC and its subtypes and associations in order to provide a pragmatic, clinically relevant and patient-centered approach to evaluation and treatment.

Aplasia cutis congenita type V: a case report and review of the literature.

Aplasia cutis congenita (ACC) is a relatively rare congenital anomaly that most commonly occurs as a solitary cutaneous defect on the scalp. Depth of involvement varies, and involvement of deeper calvarium and dural structures can be seen in more severe cases. Multiple classification systems have been devised with the Frieden Classification System being the most widely adopted. Using this system, we describe a patient that developed Type V ACC with associated fetal papyraceous. The child healed remarkably well with the application of petrolatum impregnated gauze and topical silver sulfadiazine twice daily for approximately 4 weeks. The child was noted to have no significant contractures or complications at 6-months and 1-year follow-up exams. Herein, we review the current literature on type V ACC including a discussion of treatment options.

Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate Syndrome.

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, also known as Hay-Wells syndrome, is an autosomal genetic disease with the main features of ankyloblepharon filiforme adnatum, ectodermal defects, and cleft lip/palate. The authors report a patient with 17 months old girl with AEC syndrome having ankyloblepharon, cleft and palate, and ectrodactyly with some associated features. Etiology, clinical features, differential diagnosis, and treatment have been elaborated in this clinical report.