Abstract
Objectives:
To synthesize the clinical characteristics, management, and outcomes of newborns with aplasia cutis congenita (ACC) type I.
Introduction:
ACC type I is a rare congenital condition characterized by isolated scalp defects without associated malformations. Evidence is limited and fragmented.
Methods:
We conducted a systematic review of studies reporting individual-level clinical data, including case reports, case series, and correspondence describing individual patients, following PRISMA guidelines. An additional clinical case was included.
Results:
Thirty-six studies, including 69 newborns, were analyzed. Most lesions were solitary (84.1%), located on the vertex (61.9%), superficial (55%), and more frequent in males (60.9%). Management was predominantly surgical. Complications were uncommon (21.3%), and outcomes were generally favorable.
Conclusion:
ACC type I typically presents as an isolated scalp defect with a favorable prognosis. Lesion characteristics and risk of complications should guide management.
Introduction
Aplasia cutis congenita (ACC) is a rare developmental anomaly characterized by the absence of epidermis, dermis, and, in some cases, subcutaneous tissue at birth. 1 Its pathogenesis remains uncertain, although abnormal intrauterine skin development, vascular disruption, and teratogenic exposures. 2 Lesions can appear on any site, but approximately 70% to 90% occur on the scalp vertex.3,4 The American Academy of Pediatrics estimated 1 to 3 cases per 10 000 live births, 5 while a large European population-based study from the European Surveillance of Congenital Anomalies (EUROCAT) network reported a prevalence of 5.1 per 100 000 births. 6 Such variability may reflect under-reporting, genetic and environmental differences, or methodological inconsistencies among registries.
Frieden’s 2 classification distinguishes 9 clinical subtypes of ACC based on lesion location and associated anomalies, with type I—isolated scalp defects without additional malformations—being the most frequent. The diagnosis of ACC type I is primarily clinical, and the key determinant is the absence of underlying malformations, particularly neural-tube defects or other dysraphism, which can be ruled out through cutaneous ultrasonography. 7 Although type I lesions are typically small, well-demarcated, and solitary, complications such as local infection, hemorrhage, or exposure of underlying structures may occur when lesions overlie the calvarium or dura mater. 8 Consequently, the diagnostic process must not only confirm the absence of skin but also exclude more profound or systemic anomalies to ensure appropriate therapeutic planning.
Once ACC type I is confirmed, management largely depends on lesion size and depth. 9 Small defects (<4 cm) typically heal with conservative measures, while extensive or deep lesions often require surgical reconstruction.10,11 However, evidence guiding these decisions remains anecdotal, derived mainly from isolated case reports and small series, without standardized protocols or expert consensus. This systematic review aims to integrate the existing literature on the clinical characteristics, diagnostic evaluation, management strategies, and outcomes of ACC type I in newborns, establishing an evidence-based framework to inform practice and delineate priorities for future research.
Methods
This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 12 The review protocol was prospectively registered on the Open Science Framework (OSF) platform (registration code: 10.17605/OSF.IO/JSPM3). The PRISMA checklist is provided as Supplemental Table 1. The case report was prepared in accordance with the CARE guidelines.
Ethical approval and written informed consent for publication were obtained exclusively for the reported clinical case. Approval was granted by the Institutional Review Board of the Hospital Regional de Ica, Peru (No. 335-2025-HRI/DE), and written informed consent was obtained from the patient’s parents.
Systematic Search
We conducted a comprehensive search across 4 databases: PubMed, Embase, Scopus, and Web of Science, from inception through January 6, 2025. The search strategy combined controlled vocabulary (MeSH and Emtree terms) and free-text keywords related to ACC and newborns. The main MeSH terms included “Aplasia Cutis,” “Ectodermal Dysplasia,” and “Infant, Newborn.” Corresponding free-text terms used were “aplasia cutis,” “scalp defect,” “ectodermal defect,” “congenital ectodermal,” and “neonate.” The complete search strategy for each database is detailed in Supplemental Table 2. To guide the search strategy and eligibility criteria, we defined the following PICO question: Population: newborns (0-28 days) with ACC type I; Intervention: not applicable; Comparison: not applicable; Outcomes: clinical characteristics, management approaches, complications, and prognosis.
Study Selection
Study selection was performed independently and in duplicate by 2 reviewers (ASH and DTH) using the web-based platform Rayyan (https://www.rayyan.ai) to enable blinded screening and minimize selection bias. Any discrepancies were resolved through a third author (LJUC).
Eligible studies met the following criteria: (1) studies reporting individual-level clinical data on newborns (from birth up to 28 days of life) diagnosed with ACC type I; and (2) availability of extractable sociodemographic and clinical characteristics. This included case reports, case series, and correspondence articles/brief reports describing individual patients.
In studies including multiple ACC subtypes, only data corresponding to type I cases were extracted when these could be clearly identified and analyzed separately. No language restrictions were applied.
Conference abstracts were included only when sufficient individual-level data were available.
The exclusion criteria were: (1) review articles, systematic reviews, meta-analyses, or narrative reviews; (2) studies reporting only ACC subtypes II to IX or syndromic forms without any identifiable type I case; and (3) reports lacking extractable individual-level clinical data.
For this review, ACC type I was operationally defined as isolated scalp defects without associated extracutaneous malformations, in accordance with Frieden’s 2 classification. Cases were included if they were explicitly reported as type I or if the absence of extracutaneous anomalies (eg, limb defects, syndromic features, or systemic malformations) could be clearly confirmed. Cases with underlying bony involvement (eg, calvarial defects) were not excluded, provided no extracutaneous anomalies were reported.
Risk of Bias in Individual Studies
The methodological quality and risk of bias of the included studies were assessed using the Joanna Briggs Institute (JBI) critical appraisal tools for case series 13 and case reports. 14 Each checklist item was rated as “Yes,” “No,” “Unclear,” or “Not applicable,” following the official JBI methodological guidance.
Risk of bias assessment was conducted according to the underlying study design rather than the publication format. Studies reporting individual patients were evaluated using the JBI checklist for case reports, while studies describing multiple patients were assessed using the checklist for case series.
In cases where reporting was insufficient to allow meaningful assessment, studies were considered not assessable for risk of bias and were excluded from the quality appraisal. Conference abstracts were not included in the risk of bias assessment due to their limited reporting, whereas brief reports and similar formats were assessed when sufficient methodological and clinical information was available.
The JBI tool for case series evaluates 10 domains related to study design and reporting, including the clarity of inclusion criteria, standardization of diagnostic assessment, completeness of demographic and clinical data, and adequacy of outcome and follow-up reporting. The JBI tool for case reports comprises 8 domains assessing the quality of reporting on patient demographics, clinical history, diagnostic procedures, interventions, post-treatment condition, adverse events, and key clinical lessons.
Quality assessments were conducted independently by 2 reviewers (EBE and STV), with disagreements resolved through a third author (LJUC).
Data Extraction
Data were independently extracted by 2 reviewers (ASH and DTH) using a pre-designed standardized form. Extracted information included: first author’s name, country, year of publication, newborn sex and age, clinical presentation, maternal characteristics (maternal age, obstetric history, complications during pregnancy, and delivery mode), type of treatment (conservative or surgical), and lesion depth, classified as superficial (epidermis/dermis involvement) or deep (extension into subcutaneous tissue or periosteum).2,11 Prognostic outcomes were classified as: (1) complete resolution without sequelae, (2) healing with residual alopecia, or (3) occurrence of severe complications, such as hemorrhage or infection. Categorical variables were summarized using frequencies and percentages, while continuous variables were described using means and standard deviations or medians and interquartile ranges, as appropriate. All analyses were performed using Stata/SE, version 18.0 (StataCorp LLC, College Station, TX, USA). Figures were created and formatted using graphic design software (Canva, Canva Pty Ltd, Sydney, Australia).
Data Synthesis
A narrative synthesis was conducted to integrate findings across the included studies. Descriptive analysis focused on identifying patterns in clinical presentation, management approaches, and reported outcomes, emphasizing common features and variability across cases and series. Tables were used to summarize demographic, clinical, and treatment-related characteristics, facilitating comparison among studies.
The present clinical case was included in the systematic review as part of the analyzed sample. It was described separately to detail patient demographics, lesion characteristics, diagnostic evaluation, management, and follow-up outcomes. This inclusion allowed direct comparison with previously reported cases and provided contextual support for interpreting the overall findings of the review.
Results
Case Report
A male neonate, 2 days old, was delivered by elective cesarean section at term (39 weeks of gestation). Birth measurements were within normal limits for gestational age: weight 3260 g, length 50 cm, and head circumference 34 cm. Apgar scores were 9 and 10 at 1 and 5 minutes, respectively. The mother was 40 years old, with 3 pregnancies and 2 previous live births, and a history of macrosomia and 2 prior term cesarean deliveries. She received complete prenatal care, including serologic screening and 3 obstetric ultrasounds, which revealed normal fetal development and no cranial abnormalities. The pregnancy and delivery were uneventful. The neonate required no resuscitation at birth and was transferred to rooming-in with the mother in stable condition.
On physical examination, a well-circumscribed, bilobed, ulcerated lesion was observed in the parieto-occipital region of the scalp, measuring approximately 2 × 3 cm. The lesion presented an erythematous base, absence of epidermis, and granulation tissue, with no bleeding, exudate, or crusting. There were no additional skin findings or systemic anomalies. Based on its isolated and characteristic presentation, the dermatology service established a diagnosis of ACC type I (Figure 1).
Type I aplasia cutis congenita at birth.
Initial differential diagnoses included traumatic scalp ulceration due to intrauterine pressure and neonatal herpes simplex infection. These were clinically ruled out based on the lesion’s solitary and well-demarcated morphology, absence of vesicles or bullae, and lack of systemic symptoms. No additional imaging studies (cranial ultrasound, skull radiography, or magnetic resonance imaging) or laboratory tests were requested, as the clinical evaluation showed no evidence of underlying bone or neurological involvement.
The patient underwent multidisciplinary clinical evaluation by dermatology, neonatology, pediatrics, and neurology, which confirmed the absence of associated malformations, including neural tube defects or cranial dysraphism. Family history was negative for genetic disorders, congenital malformations, or prior cases of ACC in both parental lineages.
Conservative management was initiated, consisting of daily wound care with isotonic saline cleansing, gentle washing using a 1.1% lactic acid-based syndet to restore the skin’s protective barrier, and topical application of nitrofurazone 0.2% to prevent bacterial infection. Dressings were replaced every 24 hours for 14 consecutive days under sterile conditions. The lesion exhibited progressive re-epithelialization and complete healing by secondary intention after 4 weeks, leaving a flat, atrophic, alopecic scar without infectious, hemorrhagic, or neurological complications (Figure 2).
Type I aplasia cutis congenita. (A) Day 1. (B) Day 2. (C) Day 3. (D) First week. (E) Second week. (F) Third week. (G) First month.
The patient was followed for 3 months, undergoing regular dermatologic and neurologic evaluations, during which he remained asymptomatic, with normal neurodevelopmental progress and scarring alopecia.
Systematic Review
Study Selection
A total of 3230 titles were initially identified. After removing duplicates and conducting the initial screening, followed by full-text assessment, 35 studies met the eligibility criteria and were included in the review (Figure 3). In addition, the clinical case presented in this paper was incorporated into the final analysis, resulting in a total of 36 studies. The list of reasons for exclusion of full-texts is provided in Supplemental Table 3.
Flowchart of PRISMA.
Risk of Bias Assessment
Risk of bias assessment was conducted for 23 of the 35 included studies. Twelve studies were not assessable due to insufficient reporting, including 10 case reports and 2 case series, primarily corresponding to conference abstracts and brief reports lacking adequate methodological and clinical detail.
Among the 7 assessed case series, the overall reporting quality was adequate, with a median JBI score of 7 (IQR 7-9). All studies (100%) clearly described diagnostic assessment methods, patient demographics, and clinical information. Consecutive inclusion of participants was reported in 4 studies (57.1%), and complete inclusion of eligible cases in 3 (42.9%). Follow-up outcomes and site-related information were described in 6 studies (85.7%), whereas none provided details on statistical analyses (Supplemental Figure 1).
In contrast, case reports demonstrated lower methodological quality, with a median JBI score of 4 (IQR 2-6). Most studies adequately described patient demographics (81.3%), medical history (75.0%), and clinical presentation (75.0%). However, fewer provided sufficient details on diagnostic procedures (43.8%) or post-intervention outcomes (37.5%). Descriptions of interventions or treatment procedures were limited (31.3%), and only a minority reported adverse events (25.0%). Takeaway clinical lessons were reported in 62.5% of cases (Supplemental Figure 2).
Overall, the quality of case reports was suboptimal, particularly regarding the description of interventions and outcomes. Conversely, case series generally met most quality criteria, reflecting greater methodological rigor and completeness in reporting.
Study Characteristics
A total of 36 studies, encompassing 69 newborns diagnosed with type I ACC, were included in the final analysis. The majority were case reports (n = 27; 75.0%), followed by case series (n = 9; 25.0%). Due to the wide geographic dispersion and heterogeneity of countries represented, studies were grouped by continent for descriptive purposes. Studies were predominantly conducted in Europe (n = 12; 33.3%) and Asia (n = 10; 27.8%), with fewer originating from North America (n = 7; 19.4%), South America (n = 5; 13.9%), Oceania (n = 1; 2.8%), and Africa (n = 1; 2.8%; Table 1).
Baseline Study, Maternal, and Neonatal Characteristics of Newborns with Type I ACC.
Percentages excluding missing values were calculated among reported cases.
Abbreviations: ACC, aplasia cutis congenita.
Mean ± DE.
One study contributed 2 cases to the analysis.
Additional details on publication characteristics, including study type, ethical approval, parental consent, and funding statements, are presented in Supplemental Table 4.
Maternal Characteristics
The mean maternal age was 31.2 years (SD 5.6; n = 22, 18 studies). Most mothers reported no drug exposure during pregnancy (n = 37, 80.4%). When exposure was documented (n = 9, 19.6%), the most frequently reported drugs were methimazole (n = 3, 6.5%) and carbimazole (n = 2, 4.3%), followed by valproic acid (n = 1, 2.2%) and other unspecified agents (n = 3, 6.5%). Among cases with available data (n = 46), a positive family history of ACC was reported in (n = 43, 93.5%), although this estimate is based on a limited number of studies reporting this variable. Regarding delivery type (n = 32, 24 studies), eutocic births occurred (n = 20, 62.5%) and dystocic deliveries (n = 12, 37.5%). Detailed maternal characteristics are presented in Table 1.
Newborn Characteristics
Baseline neonatal characteristics are summarized in Table 1. Among the 69 newborns, male sex predominated (60.9%). Most presented with a single lesion (84.1%), typically located on the vertex (61.9%). Lesions were mainly superficial (55.0%) and round in shape (50.0%). Additional morphological details are presented in Figure 4. Diagnosis was primarily clinical or imaging-based. Surgical management (including primary closure, grafts, and flaps) was the most common approach (84.6%). Complications were infrequent, with graft loss (12.1%) and infection (4.6%) being the most reported. At follow-up, most newborns (67.2%) had residual alopecia, while complete resolution occurred in a smaller proportion (29.7%).
Distribution (number, location, and shape) of lesions.
Discussion
Main Findings
The present systematic review, to our knowledge, represents the first structured synthesis of the clinical characteristics, management strategies, and outcomes of newborns with ACC type I. Across 36 studies encompassing 69 cases, our findings indicate that most lesions were isolated, located at the scalp vertex, and associated with a generally favorable prognosis. Surgical closure was the most frequent management approach, although conservative treatment achieved satisfactory results in selected cases.
Despite an overall moderate methodological quality, considerable heterogeneity was observed in the reporting of clinical details, diagnostic methods, and follow-up data. These findings emphasize the need for standardized clinical and reporting guidelines to ensure consistent diagnosis, management, and documentation of ACC type I across future research and clinical practice.
Comparison with Previous Literature
The findings of this review align with established descriptions of ACC type I, particularly the predominance of solitary scalp lesions located on the vertex or parietal regions, as previously reported by Frieden and subsequent epidemiologic studies.2,3,5,6 Similarly, the generally favorable outcomes observed in our synthesis reflect the benign course noted in earlier case series in which no associated malformations are present.3,5,9
Maternal exposures were uncommon, consistent with prior literature indicating that although methimazole and related antithyroid drugs are recognized teratogenic agents,15,16 they account for only a minority of reported cases. This reinforces the view that most type I cases are sporadic and lack an identifiable environmental trigger.
In contrast with existing recommendations that suggest targeted imaging—especially for midline or ulcerated lesions7,17—the studies included here demonstrated considerable variability in diagnostic evaluation, echoing previous critiques of inconsistent reporting and the absence of standardized assessment protocols. Notably, newer techniques such as ultra–high–frequency ultrasound may enhance the evaluation of lesion depth and underlying structures, yet this modality is absent mainly from published series. 18
Management patterns in our review similarly show overlap between surgical and conservative approaches, diverging from traditional practice frameworks, suggesting surgery for larger or deeper defects.2,9 This reflects the individualized decision-making described in recent clinical reports and supports the consensus that prognosis is generally excellent regardless of management strategy when lesions are appropriately monitored.9,19
By focusing exclusively on isolated type I lesions, this review helps refine the clinical profile of non-syndromic ACC and underscores persistent variability in diagnostic and treatment practices that future studies should address.
Clinical Management and Prognostic Implications
Beyond lesion-specific management, our review highlights the importance of multidisciplinary follow-up in newborns with ACC type I. Regular dermatologic and neurologic evaluations are essential to promptly identify complications such as secondary infection, hemorrhage, or delayed wound healing, particularly in deep or vertex lesions.7,20 The literature suggests that most infants maintain normal neurodevelopment despite alopecic scars, underscoring the importance of early reassurance and parental counseling in care.2,6
Moreover, accurate documentation of lesion characteristics—including size, depth, and location—can improve outcome prediction and facilitate longitudinal research. Emerging imaging modalities, particularly ultra–high-frequency ultrasound, offer a noninvasive approach to assess underlying calvarial and soft-tissue structures, which may guide selective surgical intervention and reduce procedural risk. 18
Finally, the generally favorable prognosis observed in our review supports a tailored approach: conservative management is appropriate for the majority of cases, while surgical repair should be reserved for lesions at risk of complications.20-22 These findings reinforce the need for standardized reporting frameworks and long-term follow-up protocols to optimize care, support parental counseling, and enable robust multicenter studies on ACC type I outcomes.
Future Directions and Clinical Implications
Future studies should prioritize developing management protocols for ACC type I, providing guidance on when conservative care is appropriate and when surgical intervention is indicated. There is a need for prospective, longitudinal studies to assess long-term outcomes, including scar formation, alopecia, esthetic, and functional consequences.
Multicenter collaboration and prospective registries are essential for assembling larger cohorts, which would enable the identification of risk factors for complications, such as lesion size, depth, location, and perinatal or maternal factors. These data would enable risk stratification and more individualized management plans.
Strengths and Limitations
This systematic review has several notable strengths. It represents the first comprehensive synthesis of ACC type I in newborns, integrating detailed, individual-level data from 36 studies encompassing 69 cases, including an original clinical case. By focusing on patient-level characteristics rather than aggregated data from larger observational studies, this review provides clinically actionable insights regarding lesion morphology, depth, location, maternal and neonatal factors, and management strategies. This approach offers a reference for pediatricians, dermatologists, and surgeons, supporting informed decision-making in diagnosis, risk assessment, and treatment planning.
Several limitations must also be acknowledged. Most included studies were case reports or small case series, which limits generalizability and introduces potential publication bias. Reporting was heterogeneous, with variable detail on lesion depth, diagnostic evaluation, and follow-up outcomes. Long-term outcomes beyond infancy were seldom documented, preventing comprehensive assessment of functional or cosmetic sequelae. Additionally, larger observational studies were not included because they typically report aggregated data, which would not allow extraction of patient-level clinical characteristics. The limited publications can be explained by the fact that this disease is often an isolated vertex defect, with most cases being mild and managed conservatively, leading to underreporting.
Furthermore, some variables, such as family history, were inconsistently reported across studies and were available only in a subset of cases, which may have led to overestimation and limited the interpretability of this finding. In addition, a proportion of included studies could not be assessed for risk of bias due to insufficient reporting, particularly among conference abstracts and brief reports, which may affect the overall interpretation of the methodological quality of the evidence.
Conclusion
Isolated ACC type I in newborns most commonly presents as solitary scalp lesions, predominantly on the vertex, and generally carries a favorable prognosis when appropriately monitored. Management should be guided by lesion size, depth, and risk of complications, with conservative care often sufficient for small, superficial defects and surgical intervention reserved for larger or high-risk lesions. Accurate documentation of lesion characteristics, coupled with multidisciplinary follow-up, is essential to prevent complications and support informed parental counseling. This synthesis provides clinicians with an evidence-based framework for recognizing, assessing, and managing ACC type I, while highlighting the need for prospective studies to clarify long-term outcomes and optimize care strategies.
Supplemental Material
sj-docx-1-gph-10.1177_30502225261444806 – Supplemental material for Clinical Characteristics, Management, and Prognosis of Newborns with Aplasia Cutis Congenita Type I: A Systematic Review and Case Report
Supplemental material, sj-docx-1-gph-10.1177_30502225261444806 for Clinical Characteristics, Management, and Prognosis of Newborns with Aplasia Cutis Congenita Type I: A Systematic Review and Case Report by Leonardo J. Uribe-Cavero, Fabián A. Chavez-Ecos, Marisella Chumán-Sánchez, Alexander M. Parra-Huaroto, Jesús Neyra-Leon, Dayana O. Torres-Huamani, Anthony Siguas-Huasquiche, Solange Tarazona-Vilca, Elías E. Bohorquez-Espino, Maribel Anchante-Centeno, Giancarlo Alvarado-Gamarra and Noé Atamari-Anahui in Sage Open Pediatrics
Footnotes
Acknowledgements
None.
ORCID iDs
Ethical Considerations
This study was conducted in accordance with the ethical standards of the Institutional Ethics Committee of the Cuerpo Institutional Hospital Regional de Ica, Peru, and with the 1964 Helsinki Declaration and its later amendments.
Consent to Participate
Written informed consent was obtained from the patient’s mother, as the patient is a minor, prior to participation in the study.
Consent to Publication
The patient’s mother provided written consent for the publication of the case details and accompanying images.
Author Contributions
L.J.U.C. was responsible for the study conception, design, data acquisition, analysis, and manuscript drafting. F.A.C.E., M.C.S., A.M.P.H., J.N.L., D.O.T.H., A.S.H., S.T.V., E.E.B.E., M.A.C., G.A.G., and N.A.A. contributed to data acquisition, literature review, analysis, and critical revision of the manuscript. All authors read and approved the final version of the manuscript.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data Availability Statement
Data supporting the findings of this study are available from the corresponding author upon reasonable request.
Supplemental Material
Supplemental material for this article is available online.
References
Supplementary Material
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