Large aplasia cutis congenita of the vertex conservative management.

BACKGROUND: Aplasia cutis congenita (ACC) of the vertex with bone defect is a rare and begnin anomaly that can involve the epidermis, dermis, and subcutaneous tissues of the scalp with significant bone defect Bajpai and Pal (J Pediatr Surg 38(2):e4, 2003). When associated with skull defect, this rare malformation carries the risk of severe complications such as rupture of the superior sagittal sinus or infections. METHODS AND RESULTS: We report a case of aplasia cutis congenita of the scalp with skull defect measuring 9 × 10 cm and an exposed sagittal sinus in a newborn. Both conservative and surgical methods have been proposed to treat this condition. In our case, conservative treatment was planned led to complete epithelization and the patient was healing well at 5 years of follow-up. CONCLUSIONS: ACC of the vertex with a large scalp defects present a management dilemma Rocha et al. (Clin Case Rep 3(10):841-4, 2015). Based on a review of the literature, we report this case to demonstrate that even for the largest skin and bone defects, an initial conservative approach may allow for complete wound closure without the need for early surgical intervention.

The Cardiofaciocutaneous Syndrome: From Genetics to Prognostic-Therapeutic Implications.

Cardiofaciocutaneous (CFC) syndrome is one of the rarest RASopathies characterized by multiple congenital ectodermal, cardiac and craniofacial abnormalities with a mild to severe ocular, gastrointestinal and neurological involvement. It is an autosomal dominant syndrome, with complete penetrance, caused by heterozygous pathogenic variants in the genes BRAF, MAP2K1/MEK1, MAP2K2/MEK2, KRAS or, rarely, YWHAZ, all part of the RAS-MAPK pathway. This pathway is a signal transduction cascade that plays a crucial role in normal cellular processes such as cell growth, proliferation, differentiation, survival, metabolism and migration. CFC syndrome overlaps with Noonan syndrome, Costello syndrome, neurofibromatosis type 1 and Legius syndrome, therefore making the diagnosis challenging. Neurological involvement in CFC is more severe than in other RASopathies. Phenotypic variability in CFC patients is related to the specific gene affected, without a recognized genotype-phenotype correlation for distinct pathogenic variants. Currently, there is no specific treatment for CFC syndrome. Encouraging zebrafish model system studies suggested that, in the future, MEK inhibitors could be a suitable treatment of progressive phenotypes of CFC in children. A multidisciplinary care is necessary for appropriate medical management.

Treatment and Management of Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome With Scleral Prosthetic Devices.

ABSTRACT: This case report highlights the unique application and long-term benefits of customized scleral devices in a patient with ocular complications from ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome over the span of 10 years. A 13-year-old girl with a history of EEC syndrome and ocular manifestations, including severe bilateral dry eye disease, corneal neovascularization and scarring, progressive fibrous pannus, and limbal stem cell deficiency, was examined and fitted with scleral devices. The goal of treatment was to stabilize the ocular surface, enhance vision, and improve ocular comfort. Throughout the course of treatment, there was minimal progression in ocular signs, despite interruptions in scleral device wear from application and removal challenges secondary to ectrodactyly. Customized scleral devices provided an optimal environment to support the ocular surface, improve comfort, and improve visual acuity. Further studies are required to demonstrate the benefits of scleral devices in larger populations of patients with EEC syndrome.

Cryopreserved amniotic membrane in the treatment of limb skin defects of aplasia cutis congenita: a case study.

OBJECTIVE: To report the efficacy and long-term outcomes of treating the skin defects of aplasia cutis congenita (ACC) with cryopreserved amniotic membrane (AM). METHOD: Human amnion was obtained from the caesarean delivery of a full-term healthy pregnancy and processed in a sterile laminar flow hood, and cryopreserved in liquid nitrogen. The structure of the AM was investigated histologically and the viability of the epithelial cells was assessed after cryopreservation and compared with fresh AM and with AM preserved in phosphate-buffered saline (PBS) at 4°C. The cryopreserved AM was applied onto the lower limb skin defects of a one-month old baby with ACC. Timely AM changes were performed as necessary until the wounds healed. RESULTS: The structure of the cryopreserved AM was intact, with little visible difference compared with fresh AM. The viability of the epithelial cells was partially lost but still much better retained than in those preserved in PBS at 4°C. The limb skin defects were gradually re-epithelialised upon application of the AM and were completely healed after one month. The 4-month and 2-year follow-ups presented good skin texture and colour, without hypertrophic scar formation. CONCLUSION: In this case study, cryopreservation of AM presented a well preserved stromal compartment and viable epithelial layer. It also offered features such as pain relief, good attachment and adhesiveness, improved wound healing and suppressed scar formation in the treatment of ACC skin defects.

Innovative Therapeutic Approaches for the Treatment of the Ocular Morbidities in Patients with EEC Syndrome.

Ectrodactyly-Ectodermal dysplasia-Clefting (EEC) syndrome is caused by heterozygous missense point mutations in the p63 gene, an important transcription factor during embryogenesis and for stem cell differentiation in stratified epithelia. Most of the cases are sporadic, related to de novo mutations arising during early-stage development. Familial cases show an autosomic dominant inheritance. The major cause of visual morbidity is limbal stem cell failure, which develops in the second to third decade of life. Patients often show ocular surface alterations, such as recurrent blepharitis and conjunctivitis, superficial microlesions of the cornea, and spontaneous corneal perforation and ulceration, leading to progressive corneal clouding and eventually visual loss. No definitive cures are currently available, and treatments to alleviate symptoms are only palliative. In this review, we will discuss the proposed therapeutic strategies that have been tested or are under development for the management of the ocular defects in patients affected by EEC syndrome: (i) gene therapy-based approaches by means of Allele-Specific (AS) siRNAs to correct the p63 mutations; (ii) cell therapy-based approaches to replenish the pool of limbal stem cells; and (iii) drug therapy to correct/bypass the genetic defect. However, as the number of patients with EEC syndrome is too limited, further studies are still necessary to prove the effectiveness (and safety) of these innovative therapeutic approaches to counteract the premature differentiation of limbal stem cells.

Oral management of children/adolescents with ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome: A scoping review.

AIMS: 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.

Rare diseases of ectoderm: Translating discovery to therapy.

Heritable conditions known as ectodermal dysplasias are rare and can be associated with marked morbidity, mortality, and a reduced quality of life. The diagnosis and care of individuals affected by one of the many ectodermal dysplasias presents myriad challenges due to their rarity and the diverse phenotypes. These conditions are caused by abnormalities in multiple genes and signaling pathways that are essential for the development and function of ectodermal derivatives. During a 2021 international conference focused on translating discovery to therapy, researchers and clinicians gathered with the goal of advancing the diagnosis and treatment of conditions affecting ectodermal tissues with an emphasis on skin, hair, tooth, and eye phenotypes. Conference participants presented a variety of promising treatment strategies including gene or protein replacement, gene editing, cell therapy, and the identification of druggable targets. Further, barriers that negatively influence the current development of novel therapeutics were identified. These barriers include a lack of accurate prevalence data for rare conditions, absence of an inclusive patient registry with deep phenotyping data, and insufficient animal models and cell lines. Overcoming these barriers will need to be prioritized in order to facilitate the development of novel treatments for genetic disorders of the ectoderm.

Aplasia cutis congénita: a propósito de un caso / Aplasia cutis congenita: case report / Aplasia congênita da cútis: relato do caso

La aplasia cutis congénita es una patología rara caracterizada por la ausencia de desarrollo de piel. Aunque puede localizarse en diferentes áreas del cuerpo, mayormente afecta el cuero cabelludo y puede extenderse a tejidos subyacentes. Presentamos aquí un caso clínico que se destaca por la extensión de la lesión. Se incluye la descripción del tratamiento y seguimiento del paciente.

Aplasia Cutis Congenita is a rare pathology characterized by the absence of development of the epidermis, and even though it can compromise any area of the body, it usually affects the scalp and it can be extended to the underlying tissues. We present a particular case due to the lesion size. It includes treatment description and follow-up.

A Aplasia Congênita da Cútis é uma patologia rara caracterizada pela ausência de desenvolvimento das epidermes, e embora possa se localizar em diferentes áreas do corpo, acomete principalmente o couro cabeludo e pode se espalhar para os tecidos subjacentes. Apresentamos aqui um caso clínico que se destaca pela extensão da lesão. Incluímos a descrição do tratamento e acompanhamento do paciente.

Management of nutritional and gastrointestinal issues in RASopathies: A narrative review.

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.

Orthodontic and dentofacial orthopedic treatments in patients with ectodermal dysplasia: a systematic review.

OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Ectodermal dysplasia: important role of complex dental care in its interdisciplinary management.

AIM: Despite the fact that ectodermal dysplasia (ED) is a rare disease, it is often seen in a tertiary clinic. ED affects ectodermal tissues such as skin, hair, teeth, nails, and sweat glands. Patients usually have sparse light hair, deformed nails, and dry skin. They suffer from dental abnormalities such as oligodontia (absence of 6 or more teeth) or complete anodontia; salivation can also be affected. The absence of teeth can be the overriding problem for both patients and their parents, and lead to substantial social ostracisation. This study aims to summarise the facts about the disease, especially dental treatment options based on data drawn from a representative Czech cohort. MATERIALS: The present article summarises the facts about ectodermal dysplasia (ED) in a cohort of 13 patients, where the following were evaluated: clinical manifestations of ED, pathogenic variants detected in selected candidate genes and dental treatment options from child removable dentures to fixed crowns and implants insertion. Three cases are described in detail and demonstrate approaches for different age groups. CONCLUSION: Early diagnosis and active cooperation between the geneticist and dentist will facilitate cooperation with parents and patients and assure secondary prevention. It is preferable that the geneticist understands dental treatment options and can discuss these with patients/parents.

Challenges in the management of extensive aplasia cutis congenita.

Aplasia cutis congenita (ACC) is a rare group of congenital disorders characterised by focal or widespread absence of skin, predominantly affecting the scalp. A Malay female infant was born at 37 weeks with extensive ACC, affecting 37% of total body surface area, including her scalp and trunk. There is no consensus on the management of ACC given the rarity and variable presentation. A multi-disciplinary team comprising neonatologists, paediatric dermatologists, plastic surgeons and medical laboratory scientists at the skin bank, employed a more aggressive surgical approach with the aim of avoiding potentially catastrophic morbidity, including sagittal sinus haemorrhage and brain herniation. Out of several surgical options, the team used a staged artificial dermal matrix (Integra) and cultured epithelial autograft application, followed by regular wound dressing, and eventually allowed the child to achieve complete epithelialisation of her trunk, and most of scalp before she was discharged from hospital.

Physical exercise in cardio-facio-cutaneous syndrome (CFCS): A case study

Cardio-facio-cutaneous syndrome was described in 1986 by Reynolds.1 CFC syndrome is a multiple congenital anomaly disorder that belongs to the family of RASopathy syndromes, which also includes Noonan and Costello syndromes. Mutations of the BRAF, MEK1 and MEK2 genes cause the CFC syndrome.2,3 Some clinical features of Noonan syndrome and Costello syndrome may coincide with CFCS syndrome, but CFCS has distinctive characteristics (Table 1). Some of the most common features in CFCS include dysmorphic craniofacial features, congenital heart disease, dermatological abnormalities, failure to thrive, gastrointestinal dysfunction and a wide spectrum (both in severity and type) of neurological abnormalities (neurocognitive impairment, executive dysfunction, hypotonia, coordination impairment and/or seizures). In consequence, children and adults with CFCS require multidisciplinary care from specialists and the need for comprehensive management. (AU)

Multiple aplasia cutis congenita type V and fetus papyraceous: a case report and review of the literature.

BACKGROUND: Aplasia cutis congenita is regarded as congenital focal absence of skin in the newborn, and occurrence of more than three similar skin defects is rare. The etiology is thought to be multifactorial, and precise etiopathogenesis is unknown. CASE PRESENTATION: A 13-day-old newborn Sri Lankan Tamil girl was referred to the dermatologic clinic with multiple skin defects at birth. There were six lesions on the body, and two of them had healed during intrauterine period, leaving scars. This was a second twin of her pregnancy. Her first twin fetus had demised before 19 weeks of pregnancy and was confirmed to be fetus papyraceous based on ultrasound-guided fetal assessment. The said child was thoroughly investigated and found to have no other congenital abnormalities. Chromosomal studies yielded normal findings. She was treated with tropical antibacterial ointment, and all lesions resolved spontaneously within 4 weeks, leaving scars. Physiotherapy was commenced to prevent contracture formation, and follow-up was arranged in collaboration with the plastic surgical team. CONCLUSIONS: Aplasia cutis congenita is a rare condition of uncertain etiology, but consanguinity may play a role. This report described a newborn with type V cutis aplasia congenita in whom the diagnosis was confirmed based on clinical features and revision of antenatal history. The management depends on the pattern, extent, location, severity, underlying causes, and associated anomalies.

Multidisciplinary management of a previously unreported presentation of severe aplasia cutis congenita.

Aplasia cutis congenita (ACC) is characterized by the complete or partial absence of skin at birth, with 85% of cases of ACC involving the scalp vertex. The etiology of ACC is unclear and appears to be multifactorial. We present the case of a 3-month-old boy who presented with a diagnosis of non-scalp ACC affecting approximately 80% of his total body surface area at birth. This case adds to the literature due to the patient's survival beyond the first day of life and his unique and severe distribution of defects, which led to respiratory compromise and required multidisciplinary management.

Aplasia cutis congenita: a report of two cases from National Hospital Abuja, Nigeria and review of the literature.

Aplasia cutis congenita is a rare congenital abnormality first described in 1767 by cordon. It mostly appears as a solitary lesion involving various layers of the skin and sometimes the bone on the scalp, limbs or abdomen. Genetics, environmental and exogenous causes have been implicated as potential causes. Only about 500 cases have been reported globally as of 2013. Two cases of Aplasia Cutis Congenita (ACC) who presented with scalp and bone defects at birth are reported, one in a syndromic child delivered to a consanguineous family, with associated cardiac, skin and nail anomalies (likely Adams Oliver syndrome) and the other as an isolated scalp lesion. Both were large defects managed conservatively by a multidisciplinary team. The challenges of investigating and managing such complex scalp anomalies in sub-Saharan Africa are highlighted.

Type V aplasia cutis congenita in a preterm newborn successfully resolved.

Aplasia cutis congenita (ACC) associated with fetus papyraceus is a rare subtype of aplasia cutis categorized as type V in Frieden's classification. It is characterized by stellate lesions in a symmetrical distribution over the trunk and proximal extremities. Conservative treatment is recommended, but there is not a well-defined therapeutic protocol. We report the case of a type V ACC in a preterm male newborn with lesions on the trunk and scalp successfully treated with topical 1% silver sulfadiazine and petrolatum gauze with an excellent evolution. This case associates a severe affectation of the scalp which represents a rare variant of type V ACC.

Multiple Aplasia Cutis Congenita Lesions of the Scalp: A Case Study.

Aplasia cutis congenita (ACC) is a rare condition that presents at birth as an absence of skin that does not usually involve underlying structures. Occurring in 3/10,000 live births, ACC is evenly distributed between males and females; the risk of ACC increases to 7 percent in consanguineous marriages. Up to 86 percent of lesions are found on the scalp in the midline vertex position. Lesions can also be found on the trunk and limbs, as with Adams-Oliver syndrome or accompanying epidermolysis bullosa. ACC is associated with chromosomal abnormalities and 35-50 percent of the time with trisomy 13 (Patau syndrome). This case study presents an infant with multiple ACC lesions of the scalp. The pathophysiology, treatment, potential long-term complications, and nursing considerations are discussed.

Recognizable neonatal clinical features of aplasia cutis congenita.

BACKGROUND: Aplasia cutis congenita (ACC), classified in nine groups, is likely to be underreported, since milder isolated lesions in wellbeing newborns could often be undetected, and solitary lesions in the context of polymalformative syndromes could not always be reported. Regardless of form and cause, therapeutic options have in common the aim to restore the deficient mechanical and immunological cutaneous protection and to limit the risk of fluid leakage or rupture of the exposed organs. We aimed to review our institutional prevalence, comorbidities, treatment and outcome of newborns with ACC. METHODS: We conducted a retrospective study including all newborns affected by ACC and admitted at the University Mother-Child Department from October 2010 to October 2019. Anthropometric and clinical characteristics of ACC1 versus a non-isolated ACC group were analyzed. RESULTS: We encountered 37 newborns, 16 with ACC1 versus 21 with non-isolated ACC. The incidence rate of 0.1% in ACC1 was higher than expected, while 19% of cases showed intrafamilial autosomal dominant transmission. Higher birth weight centile, though lower than reference population, being adequate for gestational age, normal Apgar score and euglycemia characterizing ACC1 resulted associated to a rapid tissue regeneration. Non-isolated ACC, in relation to concomitant congenital anomalies and higher prematurity rate, showed more surgical and medical complications along with the risk of neonatal death. Specifically, newborns with ACC4 were characterized by the frequent necessity of abdominal wall defect repair, responsible for the occurrence of an abdominal compartment syndrome. CONCLUSION: Prompt carefully assessment of the newborn with ACC in order to exclude concomitant other congenital malformations, provides clues to the underlying pathophysiology, and to the short-term prognosis. Family should be oriented toward identification of other family members affected by similar pathology, while obstetric history should exclude initial multiple pregnancy with death of a co-twin, placental anomalies and drug assumption. Molecular-genetic diagnosis and genetic counseling are integrative in individualized disease approach.

Successful Allogeneic Stem Cell Transplantation in Nuclear Factor-Kappa B Essential Modulator Deficiency Syndrome After Treosulfan-Based Conditioning: A Case Report.

BACKGROUND: X-linked EDA-ID1 (ectodermal dysplasia, anhidrotic, with immunodeficiency 1, Online Mendelian Inheritance in Man [OMIM] 300291), or NEMO (nuclear factor kappa B essential modulator) deficiency syndrome, is caused by mutations in the IKBKG/NEMO gene. We report the case of a boy with EDA-ID1 who underwent allogeneic stem cell transplantation. METHODS: In early infancy, the patient developed an atypical, severe, initial manifestation resembling Omenn syndrome with infections, and he underwent allogeneic stem cell transplantation from an unrelated 9 of 10 HLA matched donor with a mismatch in the DQB1 allele after conditioning with treosulfan, fludarabine, thiotepa, and antithymocyte globulin (Grafalon). The post-transplant period was complicated by cytomegalovirus replication and mild, grade 2 graft vs host disease. Because of NEMO deficiency syndrome-associated enteropathy and continuous weight loss, parenteral nutrition was started and the patient was fed an elemental formula and a gluten-free diet. Over a period of 3 years, the patient had 7 incidents of blood stream infections caused by Staphylococci or gut-derived Gram-negative flora, with 1 incident of septic shock caused by Escherichia coli. The blood stream infection stopped after gastrointestinal tract decontamination was done once per month for 7-day courses alternately with rifaximin, vancomycin, and gentamicin sulfate. CONCLUSIONS: Patients with NEMO deficiency syndrome require very complex, multidisciplinary care, and immunodeficiency correction can only be observed as one of the critical points in patient care. Developmental problems, enteropathy with the need for intravenous hyperalimentation, and specific interventions for other clinical manifestations of multifaceted syndrome are needed for proper care.