Aplasia Cutis Research Articles

A Novel Approach to Aplasia Cutis Congenita With PolyNovo BTM.

Aplasia cutis congenita (ACC) is a rare congenital condition characterized by the absence of skin and subcutaneous tissue, typically affecting the scalp. This case report presents a female infant born at 38+3 weeks with a posterior midline scalp defect measuring 15×12.5mm, involving skin, subcutaneous tissue, and calvarium. The defect was managed with NovoSorb Biodegradable Temporising Matrix (BTM). Initially, the plan involved a subsequent skin graft; however, the defect epithelized without grafting. By 2 months, the wound had healed completely, and by 6 months, the underlying bone had ossified. ACC presents with significant variability, and management strategies range from conservative treatment to surgical intervention depending on defect size. This case demonstrates the successful use of a fully synthetic dermal substitute in managing full-thickness scalp defects, providing a novel, effective option for treating ACC without requiring grafting.

Biotinidase Deficiency and Aplasia Cutis Congenita with Ecterodactyly Syndrome (ACCES) in a case of Moya Moya Disease: A Missing Link

Biotinidase Deficiency (BD) is a rare autosomal recessive disorder caused by mutations in the BTD gene, leading to impaired biotin recycling and disruption in energy metabolism, oxidative stress, and blood-brain barrier function. This condition increases the risk of neurovascular events such as strokes. In parallel, the UBA2 gene's loss of function, through various mutations, results in Aplasia Cutis Congenita with Ectrodactyly (ACCES) syndrome, an autosomal dominant disorder with highly variable expressivity. ACCES syndrome commonly presents with scalp defects and less frequently with ectrodactyly, alongside other subtle skeletal anomalies, early growth deficiency, and neurodevelopmental delay. This case report discusses a 6-year-old child presenting with an acute stroke and distinct dysmorphic features, highlighting a rare association between Biotinidase Deficiency and ACCES syndrome, which likely contributed to the development of Moya Moya Disease (MMD), a rare progressive cerebrovascular disorder. The case suggests that the combination of neurovascular stress due to both BD and ACCES may increase the risk of stroke and MMD in affected individuals. This underscores the importance of recognizing overlapping genetic conditions that could lead to severe neurovascular complications.

Bullous aplasia cutis congenita: A rare entity in the paradigm of congenital skin defect disorder

Bullous aplasia cutis congenita: A rare entity in the paradigm of congenital skin defect disorder

Line-Field Optical Coherence Tomography: Usefulness in the Non-Invasive Differential Diagnosis of Congenital Alopecia of Infancy.

Soon after birth, the clinical differential diagnosis between sebaceous of Jadassohn (NSJ), congenital triangular alopecia (CTA) and aplasia cutis congenita (ACC) may be challenging. A certain overlap of standard dermoscopic features can occur, especially in atypical cases, depending on scalp skin morphology and maturation age. The recently developed line-field confocal optical coherence tomography (LC-OCT) can provide morphological skin details with cellular resolution trough a rapid non-invasive examination. To assess the LC-OCT features of 6 cases of congenital alopecia of different aetiologies, with both typical and atypical clinical appearance. A non-invasive imaging examination combining standard dermoscopy, high-resolution videodermoscopy (HRVD) and LC-OCT was realized in 7 babies presenting for congenital alopecia with overlapping features, aged between 5 months and 5 years. Based on the specific LC-OCT features, and supported by HRVD features, a diagnosis of NSJ, congenital triangular alopecia (CTA) and AC) were made in 4, 2 and 1 case, respectively. The combined LC-OCT plus HRVD non-invasive imaging bring the advantage to have a real time diagnosis, to set the proper management and allows to avoid a skin biopsy in the perinatal age/first years of life at delicate skin site.

Diagnosis and Management of Hair Loss in Pediatric

Background: Hair loss can occur in pediatric and adult populations and may have different patterns. The causes of hair loss in pediatric patients include tinea capitis, alopecia areata, telogen effluvium, traction alopecia, anagen effluvium, androgenetic alopecia, loose anagen syndrome, short anagen syndrome, congenital aplasia cutis, congenital triangular alopecia, atrichia congenita, congenital hypotrichosis, and transient neonatal hair loss.Purpose: to understand etiologies of hair loss in pediatrics, and to determine the appropriate examinations for diagnosing and managing hair loss in children.Review: Hair loss in children can be categorized as congenital or acquired. Congenital hair loss is classified based on distribution, while acquired hair loss is classified as either scarring or non-scarring. Hair loss complications in children can be irreversible. The diagnosis of hair loss in pediatric patients includes anamnesis, physical examination, and supporting examinations. The supporting examinations used for diagnosis include fungal cultures, hair pull tests, hair tug tests, light microscopy, and trichoscopy. Conclusion: There are numerous causes of hair loss in pediatric patients that need to be identified before appropriate management can be implemented. The management of hair loss requires a holistic approach, including psychosocial support. Correct diagnosis and treatment of pediatric hair loss can prevent a decrease in the patient's quality of life.

A Case of Nonsyndromic Aplasia Cutis Congenita (Epitheliogenesis Imperfecta) in a Large White Yorkshire Piglet

Nonsyndromic Aplasia Cutis Congenita (Epitheliogenesis Imperfecta) are congenital, circumscribed hypoplastic defects of multiple or deeper skin layers in swine. Although swine have been reported to have epitheliogenesis imperfecta, little is known about this condition in the literature. A new born Large White Yorkshire female piglet was presented with glistening red, well-demarcated discontinuities in the skin on the frontal skull with no apparent bleeding which was managed by conservative treatment.

Expanding the phenotypic spectrum of NOTCH1 variants: clinical manifestations in families with congenital heart disease.

Pathogenic variants in NOTCH1 are associated with non-syndromic congenital heart disease (CHD) and Adams-Oliver syndrome (AOS). The clinical presentation of individuals with damaging NOTCH1 variants is characterized by variable expressivity and incomplete penetrance; however, data on systematic phenotypic characterization are limited. We report the genotype and phenotype of a cohort of 33 individuals (20 females, 13 males; median age 23.4 years, range 2.5-68.3 years) from 11 families with causative NOTCH1 variants (9 inherited, 2 de novo; 9 novel), ascertained from a proband with CHD. We describe the cardiac and extracardiac anomalies identified in these 33 individuals, only four of whom met criteria for AOS. The most common CHD identified was tetralogy of Fallot, though various left- and right-sided lesions and septal defects were also present. Extracardiac anomalies identified include cutis aplasia (5/33), cutaneous vascular anomalies (7/33), vascular anomalies of the central nervous system (2/10), Poland anomaly (1/33), pulmonary hypertension (2/33), and structural brain anomalies (3/14). Identification of these findings in a cardiac proband cohort supports NOTCH1-associated CHD and NOTCH1-associated AOS lying on a phenotypic continuum. Our findings also support (1) Broad indications for NOTCH1 molecular testing (any familial CHD, simplex tetralogy of Fallot or hypoplastic left heart); (2) Cascade testing in all at-risk relatives; and (3) A thorough physical exam, in addition to cardiac, brain (structural and vascular), abdominal, and ophthalmologic imaging, in all gene-positive individuals. This information is important for guiding the medical management of these individuals, particularly given the high prevalence of NOTCH1 variants in the CHD population.

Large skin defect in Type V aplasia cutis congenita treated with conservative treatment: a case report

Aplasia cutis congenita (ACC) is a congenital disorder that can be classified into nine types, with Type I ACC being the most common. Type V ACC associated with fetus papyraceus is a rare subtype of ACC. We report the case of a Type V ACC in a male newborn with extensive abdominal skin defects. The patient received conservative treatment using hydrogel foam and silicone foam dressings. Approximately five weeks later, the patient was discharged when more than 60% of the skin had completed epithelialization. After discharge from West China Second University Hospital, Chengdu , the patient continued to be followed up regularly at the Burns and Plastic Surgery Clinic at local hospital in Gansu. We followed up the child by telephone. After 4 months of follow-up, scar tissue formation was observed in the trunk area. The infant is 2 years and 5 months old now, physical examination did not reveal any organ problems.

Aplasia Cutis Congenita Associated with a Fetus Papyraceus: A Case Report

Aplasia Cutis Congenita Associated with a Fetus Papyraceus: A Case Report

Multiple congenital anomalies in a late-preterm neonate: A case of possible carbimazole embryopathy

ABSTRACT The use of carbimazole in the treatment of hyperthyroidism in pregnant women is associated with several congenital anomalies, especially when used during early pregnancy. Some of the reported congenital anomalies include aplasia cutis congenita, choana/esophageal atresia, facial dysmorphism, and cardiovascular/gastrointestinal anomalies. We report the case of a 17-day-old late-preterm neonate who presented with complaints of difficulty in breathing, darkening of the lips/extremities, and abnormal facies observed since birth. The mother had been on tablet carbimazole 20 mg daily for the treatment of hyperthyroidism until the fifth week of gestation from the time she was confirmed to be pregnant. Physical examination and further evaluations revealed multiple congenital anomalies, including facial dysmorphism, bilateral arthrogryposis of the lower limbs, micropenis, complex congenital heart disease, and intestinal obstruction. This case report, therefore, highlights the need to avoid the use of imidazole derivatives such as carbimazole during the pre-conception period as well as in the first trimester of pregnancy.

Non-surgical management of severe aplasia cutis congenital accompanied by a bone defect – a case study

Background and objectives. Aplasia cutis congenita (ACC) is a rare developmental disorder that is not fully understood. It is part of a diverse group of conditions characterized by the congenital absence of THE epidermis, dermis, and occasionally subcutaneous tissues or bone, often affecting the crown of the scalp. It frequently presents as an isolated condition but can also be associated with a syndrome. Among patients, scalp involvement is common; however, large scalp defects with skull involvement are uncommon. Materials and methods. We report the case of a newborn delivered at full term by cesarean section, 3200g, in Mangalia Municipal Hospital, later transferred to the Constanta Neonatology Department, Neonatal Intensive Care department, for 3 injuries with lack of substance, both in tegument and bone, of different sizes, at the level of the vertex and the occiput. Results. Given the fragile age, a conservative management approach was chosen. The wound was meticulously cleaned daily using sterile water, and a self-adhesive absorbent dressing with hydrocolloid was applied. This dressing promoted granulation and epithelialization, adjusting dynamically to the lesion size. The newborn remained hospitalized for 35 days until the closure of the most extensive skin lesion at the vertex. Conclusions. Aplasia cutis congenita can be managed using various treatment approaches, but a consensus on the optimal strategy remains elusive. While conservative treatment has been proposed, several authors have highlighted its limitations. The choice between conservative and surgical management should be personalized, considering factors such as lesion size, location, underlying etiology, and related abnormalities.

Skin Expander for Scalp Reconstruction: Reappraisal of a Reconstructive Procedure for Aplasia Cutis Congenita.

Aplasia cutis congenita (ACC) is a heterogeneous group of congenital disorders characterized by the absence of epidermis, dermis, appendages, subcutaneous tissue, and bone. The aim of the study is to describe a clinical report of ACC of the scalp treated with skin expanders. In October 2019, a 16-year-old female patient underwent scalp expansion with 2 rectangular devices (150 and 250cm3; Radovan Mentor-Johnson&Johnson). The inflation started 30 days after surgery and continued once every 7 to 10 days to gain 10% of overexpansion. After 3 months, the patient underwent the second surgical step with the expanded scalp transposed to close the defect. Clinical examination 6 months after surgery revealed an acceptable cosmetic result with a hidden surgical scar and hair growth in the previous area of frontoparietal alopecia. Skin expander for the reconstruction of extensive ACC defects of the scalp is a valid procedure.

Amniotic membrane dressings for treatment of aplasia cutis in newborns.

Aplasia cutis congenita (ACC) is a rare congenital skin defect characterized by a focal or extensive absence of the epidermis, dermis, and occasionally, subcutaneous tissue. When the wound caused by this defect is wide or deep, various treatments are used, including skin grafting. The amniotic membrane (AM) is a biological dressing that facilitates re-epithelialization as it contains mesenchymal cells and numerous growth factors. To report the efficacy of AM dressings in treating the skin defects of ACC. This study was conducted on five neonates diagnosed with ACC born between 2018 and 2022, referred to the Children's Medical Center in Tehran, Iran. AM dressings were applied on wounds larger than 1 cm2. The wounds were assessed weekly and, if required, an additional AM dressing was applied. The skin defects gradually re-epithelialized after application of the AM. The complete healing process took around 3.5 weeks on average. No hypertrophic scarring was observed. The application of AM dressing resulted in satisfactory cosmetic outcomes, with no hypertrophic scar formation. Complete healing occurred in all cases except one. The length of the hospital stay ranged from 2 to 6 weeks, depending on the size of the wound.

BTB domain mutations perturbing KCTD15 oligomerisation cause a distinctive frontonasal dysplasia syndrome.

KCTD15 encodes an oligomeric BTB domain protein reported to inhibit neural crest formation through repression of Wnt/beta-catenin signalling, as well as transactivation by TFAP2. Heterozygous missense variants in the closely related paralogue KCTD1 cause scalp-ear-nipple syndrome. Exome sequencing was performed on a two-generation family affected by a distinctive phenotype comprising a lipomatous frontonasal malformation, anosmia, cutis aplasia of the scalp and/or sparse hair, and congenital heart disease. Identification of a de novo missense substitution within KCTD15 led to targeted sequencing of DNA from a similarly affected sporadic patient, revealing a different missense mutation. Structural and biophysical analyses were performed to assess the effects of both amino acid substitutions on the KCTD15 protein. A heterozygous c.310G>C variant encoding p.(Asp104His) within the BTB domain of KCTD15 was identified in an affected father and daughter and segregated with the phenotype. In the sporadically affected patient, a de novo heterozygous c.263G>A variant encoding p.(Gly88Asp) was present in KCTD15. Both substitutions were found to perturb the pentameric assembly of the BTB domain. A crystal structure of the BTB domain variant p.(Gly88Asp) revealed a closed hexameric assembly, whereas biophysical analyses showed that the p.(Asp104His) substitution resulted in a monomeric BTB domain likely to be partially unfolded at physiological temperatures. BTB domain substitutions in KCTD1 and KCTD15 cause clinically overlapping phenotypes involving craniofacial abnormalities and cutis aplasia. The structural analyses demonstrate that missense substitutions act through a dominant negative mechanism by disrupting the higher order structure of the KCTD15 protein complex.

Aplasia cutis congenita as a complication of early interstitial laser embryo reduction in a case of monochorionic triamniotic triplet pregnancy ‒ a case report

Abstract Objectives Monochorionic multiple pregnancies are being increasingly encountered. Early embryo reduction by interstitial laser is an option of therapeutic intervention. The patient counseling is mainly focused on miscarriage and fetal demise but this case report highlights that the counseling also needs to mention the possibility of developing Aplasia cutis congenita post intervention and that interstitial laser though technically feasible can have rare complications. Case presentation This was a uncommon form of twinning diagnosed as monochorionic triamniotic triplet pregnancy where the parents wanted to continue with a single fetus. Interstitial laser was performed in two of the embryos, which became papyraceous. The newborn on delivery was seen to have extensive skin scarring on the trunk which was diagnosed as Aplasia cutis congenita. Conclusions Awareness on complications on early interstitial laser procedures beyond miscarriage and fetal demise and the psychological impact on the parents of seeing the scarred neonate for the first time, if they have not been made aware of this complication.

Gastrointestinal Tract Granular Cell Tumor in the Pediatric Population: A Multicenter Experience.

Pediatric granular cell tumors (GCT) involving the gastrointestinal tract (GIT) are rare with limited case report/series reported to date. Multicenter retrospective study of pediatric GIT GCT. A total of 10 cases were included in the study with a median age of 13.5 years (range: 7-18 years) and were predominantly female patients (60%). In half of the patients no significant medical history was present with the remaining 5 having Crohn disease (10%), eosinophilic esophagitis (EoE) (10%), Crohn disease and EoE (10%), growth hormone deficiency (10%), and aplasia cutis congenita (10%). The GCT median size was 1.3 cm (range: 1-1.6 cm) and were more commonly located in the esophagus (70%) followed by the stomach (20%) and rectum (10%). Most of the cases showed round/polygonal tumor cells with abundant granular cytoplasm, and none of the cases had nuclear atypia, increased mitotic activity, or tumor cell necrosis. None of our cases received specific therapy for GCT other than clinical follow-up, and none of the patients had evidence of local recurrence or metastatic disease. We present our multicenter experience with GIT GCT, all cases had a benign course. Interestingly, 4 of the esophageal GCT cases (including 2 patients with EoE) showed an eosinophil-rich esophagitis in the underlying mucosa.

Aplasia Cutis Congenita of the Lumbosacral Area with “Hair Collar Sign” but No Underlying Neuroectodermal Defects

Aplasia Cutis Congenita of the Lumbosacral Area with “Hair Collar Sign” but No Underlying Neuroectodermal Defects

Adams-Oliver Syndrome (OSA)

Introduction: Adams-Oliver's syndrome (SAO) is a rare genetic condition characterized by the association of lumb anomalies and Aplasia cutis congenita in vertex, often accompanied by underlying ossification defect and vascular lesions. The objective through this new observation is to describe the clinical, radiological, therapeutic and evolutionary elements according to what was described up to there in the literature.
 Observation: Female newborn child, stemming from a pregnancy followed with normal obstetric ultrasounds. He presents a scalp agenesis, underlying cranial bone aplasia and toes hypoplasia with syndactyly. The association of these two major criteria allowed making the diagnosis of SAO. Moreover, she presents disjointed and large sagittal suture with left parietal bone borders hypoplasia. The notion of periventricular bleeding. The rest of the balance sheet deformation, namely the abdominal ultrasound and echocardiography was without anomalies. The newborn was sent in neurosurgery for restorative treatment, which will be planned at the age of 3 months.
 Discussion and Conclusion: This observation illustrates sporadic and not complicated SAO. The absence of complete gene mapping in SAO and therefore of any genetic counseling, prenatal morphological ultrasound, is making important in evolutionary terms of subsequent pregnancies.

KCTD1/KCTD15 complexes control ectodermal and neural crest cell functions, and their impairment causes aplasia cutis.

Aplasia cutis congenita (ACC) is a congenital epidermal defect of the midline scalp and has been proposed to be due to a primary keratinocyte abnormality. Why it forms mainly at this anatomic site has remained a long-standing enigma. KCTD1 mutations cause ACC, ectodermal abnormalities, and kidney fibrosis, whereas KCTD15 mutations cause ACC and cardiac outflow tract abnormalities. Here, we found that KCTD1 and KCTD15 can form multimeric complexes and can compensate for each other's loss and that disease mutations are dominant negative, resulting in lack of KCTD1/KCTD15 function. We demonstrated that KCTD15 is critical for cardiac outflow tract development, whereas KCTD1 regulates distal nephron function. Combined inactivation of KCTD1/KCTD15 in keratinocytes resulted in abnormal skin appendages but not in ACC. Instead, KCTD1/KCTD15 inactivation in neural crest cells resulted in ACC linked to midline skull defects, demonstrating that ACC is not caused by a primary defect in keratinocytes but is a secondary consequence of impaired cranial neural crest cells, giving rise to midline cranial suture cells that express keratinocyte-promoting growth factors. Our findings explain the clinical observations in patients with KCTD1 versus KCTD15 mutations, establish KCTD1/KCTD15 complexes as critical regulators of ectodermal and neural crest cell functions, and define ACC as a neurocristopathy.

Genome-wide association analysis unveils candidate genes and loci associated with aplasia cutis congenita in pigs

BackgroundAplasia cutis congenita (ACC) is a rare genetic disorder characterized by the localized or widespread absence of skin in humans and animals. Individuals with ACC may experience developmental abnormalities in the skeletal and muscular systems, as well as potential complications. Localized and isolated cases of ACC can be treated through surgical and medical interventions, while extensive cases of ACC may result in neonatal mortality. The presence of ACC in pigs has implications for animal welfare. It contributes to an elevated mortality rate among piglets at birth, leading to substantial economic losses in the pig farming industry. In order to elucidate candidate genetic loci associated with ACC, we performed a Genome-Wide Association Study analysis on 216 Duroc pigs. The primary goal of this study was to identify candidate genes that associated with ACC.ResultsThis study identified nine significant SNPs associated with ACC. Further analysis revealed the presence of two quantitative trait loci, 483 kb (5:18,196,971–18,680,098) on SSC 5 and 159 kb (13:20,713,440–207294431 bp) on SSC13. By annotating candidate genes within a 1 Mb region surrounding the significant SNPs, a total of 11 candidate genes were identified on SSC5 and SSC13, including KRT71, KRT1, KRT4, ITGB7, CSAD, RARG, SP7, PFKL, TRPM2, SUMO3, and TSPEAR.ConclusionsThe results of this study further elucidate the potential mechanisms underlying and genetic architecture of ACC and identify reliable candidate genes. These results lay the foundation for treating and understanding ACC in humans.