Bart Syndrome: A Case with Extensive Skin Lesions and Multiple Congenital Anomalies in a Preterm Neonate

Abstract

Background

Epidermolysis bullosa (EB) with congenital absence of skin (CAS) (Bart syndrome) is a rare condition characterized by the coexistence of any form of EB and congenital localized absence of skin, also known as aplasia cutis congenita (ACC). It represents a subset of ACC with associated epidermal fragility, often leading to blisters, nail dystrophy, and additional congenital anomalies.

Case Presentation

We describe a case of a 2-day-old male preterm infant who presented with CAS over the cheeks, lower abdomen, and extremities. Blisters were noted on the left hand fingers, accompanied by nail dystrophy. The clinical presentation was suggestive of a skin fragility disorder. Laboratory investigations and imaging studies revealed multiple associated congenital anomalies. Based on the clinical findings, a diagnosis of Bart syndrome was established.

Conclusion

EB with CAS (Bart syndrome) should be considered in neonates presenting with congenital skin absence and signs of epidermal fragility. Early recognition and multidisciplinary management are crucial for addressing potential complications and improving patient outcomes.

Introduction

Epidermolysis bullosa (EB) with congenital absence of skin (CAS) (Bart syndrome) is a rare genetic condition characterized by the simultaneous occurrence of any form of EB and congenital localized absence of skin, also known as aplasia cutis congenita (ACC) [1]. The syndrome was first described by Bart et al. [2] in 1966 after he studied a family with multiple affected members, highlighting its hereditary nature. ACC is a heterogeneous group of disorders, and in 1986, Frieden [3] classified ACC into nine groups based on the location of skin lesions and associated anomalies, with EB with CAS designated as Group 6.

Clinically, EB with CAS manifests with blistering of the skin and/or mucous membranes, absence of skin predominantly on the extremities, and nail dystrophy [3]. The skin lesions are often present at birth and may affect various body parts, leading to significant morbidity due to risk of infection and fluid loss. In more severe cases, particularly those linked to junctional EB, additional congenital anomalies can occur. These may include amniotic bands, arthrogryposis, renal abnormalities, pyloric atresia, and malformations of the ears and nose [1]. Such complexities can complicate clinical management and impact the overall prognosis of affected individuals.

The mode of inheritance for EB with CAS is typically autosomal dominant, which means a single copy of the altered gene in each cell is sufficient to cause the disorder. However, de novo mutations have been documented, resulting in sporadic cases without a prior family history of the disease [4, 5]. This genetic variability underscores the importance of genetic counseling and molecular diagnostics in managing the condition and advising affected families.

Due to its rarity and clinical overlap with other forms of EB and ACC, EB with CAS may be underdiagnosed or misdiagnosed. Early recognition is essential for implementing appropriate wound care, preventing complications, and providing families with accurate prognostic information. Multidisciplinary management involving dermatologists, geneticists, and pediatric surgeons may be required for optimal care [4].

Although EB with CAS has classically been described as an autosomal dominant disorder, cases presenting with extensive congenital anomalies, as observed in this patient, are more commonly inherited in an autosomal recessive pattern, as noted in Frieden’s classification [3] and supported by Bolognia et al. [1, p. 740–741]. This report presents a case of EB with CAS in a preterm infant with severe congenital anomalies, contributing to the existing literature and emphasizing the need for heightened clinical awareness and early intervention in such cases.

Case Presentation

A male preterm infant was delivered at 32 weeks of gestation to a mother with gestational diabetes mellitus and antiphospholipid syndrome. The maternal history was significant for three previous spontaneous abortions. During the pregnancy, the mother was on a regimen of prednisolone, aspirin, and enoxaparin for anticoagulation. The parents were consanguineous, with no family history of similar conditions. There was no history of maternal radiation exposure during the pregnancy.

At birth, the infant presented with a complete absence of skin over the cheeks, lower abdomen, and extremities, along with blistering on the left hand fingers. He was admitted to the neonatal intensive care unit due to respiratory failure and intrauterine growth restriction, requiring mechanical ventilation. The infant was administered two doses of surfactant. On physical examination, the neonate’s weight was 1.1 kg, length was 39 cm, and head circumference was 27 cm. Vital signs included a temperature of 36.9°C, blood pressure of 90/45 mm Hg (mean arterial pressure: 60 mm Hg), respiratory rate of 50 breaths per minute, and oxygen saturation of 95% on mechanical ventilation. Local examination revealed a distended abdomen with visible veins and telangiectasia. Dermatologic examination identified well-demarcated areas of skin absence over the cheeks, nose, lower abdomen, and bilateral upper and lower extremities. Visible vascular structures were noted over the lower limbs as well as blisters on the lateral fingers of the left hand (Fig. 1). The scalp and mucous membranes were unaffected.

Fig. 1.

Clinical features of Bart syndrome in a neonate. a Absence of skin over the cheeks and nose. b Absence of skin on the lower abdomen and extremities. c Visible vascular structures over the lower limbs. d Blisters over the left hand fingers with nail dystrophy.

Initial laboratory investigations revealed a hemoglobin level of 14.9 g/dL, total leukocyte count of 12.7 × 10³/µL, and platelet count of 203 × 10³/µL. However, subsequent results showed deterioration, with hemoglobin dropping to 4 g/dL and platelet count to 67 × 10³/µL. Additional investigations demonstrated renal failure (serum creatinine: 773 µmol/L). Ultrasonography identified a right multicystic dysplastic kidney and a left hydronephrotic kidney. Echocardiography revealed a large patent ductus arteriosus and a chest radiograph showed pulmonary infiltration with congestion. Furthermore, the patient was diagnosed with a tracheoesophageal fistula.

The patient was managed conservatively. Wound care included the application of nonadhesive dressings, Vaseline, and 2% fusidic acid cream to the affected areas. General supportive measures were provided to minimize trauma and invasive procedures. On the 19th day of life, the infant succumbed to complications including anemia, thrombocytopenia, and renal failure.

Discussion

EB with CAS is a rare genetic disorder characterized by the presence of sharply defined, shiny red ulcerative patches with occasional blistering that affect the skin and mucous membranes. It is often accompanied by congenital nail absence or dystrophy [1]. The syndrome has been linked to a variety of congenital anomalies, including wide-set eyes, a flattened nose, a broad nasal root, pyloric atresia, and stunted ear development [2]. While involvement of the scalp is the most common manifestation in cases of ACC, accounting for approximately 84% of cases, the trunk and extremities may also be affected. ACC can present unilaterally or, less commonly, bilaterally [6–8].

Tracheoesophageal fistula is more commonly associated with type I ACC and is extremely rare in type VI, as seen in Bart syndrome [9]. Its presence in our case sheds lights on the unusual severity and complexity of this presentation.

The diagnosis of EB with CAS is predominantly clinical, relying on its characteristic signs and symptoms, as was the case with our patient [5]. In certain instances, a skin biopsy may be required to determine the specific subtype EB through immunofluorescence staining or electron microscopy. Genetic testing is an essential tool to identify the causative gene mutation, which aids in confirming the diagnosis [4, 10].

The syndrome typically follows an autosomal dominant inheritance pattern; however, sporadic cases resulting from de novo mutations are well documented [10]. Christiano and colleagues [11] conducted a mutation analysis on affected individuals from the original family described with Bart syndrome. Their findings identified a guanine-to-adenine transition within exon 73 of the COL7A1 gene, leading to the substitution of glycine with arginine in the triple-helical domain of type VII collagen [4]. This mutation underscores the classification of EB with CAS as a clinical variant of dominant dystrophic EB in this family. The COL7A1 gene, located on chromosome 3, encodes the pro-α1 (VII) chain, a critical component of type VII collagen. Type VII collagen plays an essential role in the formation of anchoring fibrils that connect the epidermis to the dermis. A deficiency or abnormality in type VII collagen disrupts fibril formation, impairing the connection between the two skin layers. As a result, even minor trauma or friction can lead to separation of the layers, causing blistering and subsequent scarring during the healing process [11].

Given the multisystem involvement, including renal anomalies, tracheoesophageal fistula, and hematologic complications, differential diagnoses such as VACTERL association and other syndromic congenital anomalies should be considered. The etiology of ACC, a hallmark feature of EB with CAS, is multifactorial and may involve intrauterine infections, trauma, teratogens, vascular impairments, and genetic abnormalities [10].

Management of Bart syndrome requires a comprehensive approach combining conservative measures, secondary intention healing, and, when necessary, surgical interventions. The primary goals of treatment are to accelerate wound healing, reduce the risk of infection, and minimize scarring [1, 2]. Conventional management strategies include meticulous wound care and infection prevention using topical agents like bacitracin ointment or silver sulfadiazine cream [3, 4]. Petrolatum gauze is considered the optimal dressing material, as it maintains a moist wound environment, prevents trauma, and reduces the risk of contact dermatitis [3]. In our patient, nonadhesive dressings, Vaseline, and fusidic acid cream were applied to the exposed skin areas. General supportive measures, such as minimizing invasive procedures and ensuring gentle handling, were also emphasized. Despite these efforts, the patient succumbed to complications, including anemia and thrombocytopenia, on the 19th day of life.

Prognosis in EB with CAS varies depending on the extent and severity of ACC, the EB subtype, associated abnormalities, and the effectiveness of management strategies. While the prognosis is generally favorable in mild cases, severe cases, particularly those with systemic involvement, may result in significant morbidity and mortality [6, 12].

Conclusion

Bart syndrome is a rare genetic disorder with a broad spectrum of clinical presentations, including the severe and uncommon combination of anomalies observed in this case. This report highlights a unique presentation in a preterm infant, characterized by extensive ACC, blistering, renal failure, and a tracheoesophageal fistula. Such rare and complex manifestations highlight the need for increased clinical awareness and a multidisciplinary approach to management. By sharing this case, we aim to expand the understanding of Bart syndrome’s diverse phenotypic spectrum and improve recognition of its rarer forms.

Statement of Ethics

Informed consent was obtained from legal guardian for the publication of this case report. The legal guardian was informed that the identity would be kept confidential, and all personal identifying information would be removed to ensure anonymity. They were also made aware that the case report may be published in medical literature or presented at medical conferences. They were informed that their participation was voluntary and that they could withdraw their consent at any time. Written consent for the use of photographs in this manuscript has been obtained from the patient’s legal guardian depicted in the images. The patient’s legal guardian has been assured of anonymity and understands that these images will be used exclusively for educational and illustrative purposes within this manuscript. This study was conducted in accordance with the World Medical Association Declaration of Helsinki. As per institutional and national guidelines, single case reports are exempt from ethical approval at Al-Noor Specialist Hospital. Additionally, this retrospective review of patient data did not require ethical approval in accordance with local and national regulations. Written informed consent was obtained from the patient’s legal guardian for the publication of this case report, including the use of clinical data and images. The patient’s legal guardian was informed about the purpose of the publication and agreed that no identifying information would be disclosed. They understood that the case details might be published in medical literature or presented at conferences. The CARE Checklist for this case report is available as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000547618).

Conflict of Interest Statement

The authors do not have any conflict of interest.

Funding Sources

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Author Contributions

D.A., A.A., H.Y.N., and H.A. equally contributed to conceptualization, data collection, writing of the manuscript, supervision, reviewing, and editing of the final manuscript.

Funding Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Data Availability Statement

All data generated or analyzed during this study are included in this published article and its supplementary information files. Further inquiries can be directed to the corresponding author, Houriah Nukaly.