Familial Epidermolysis Bullosa With Aplasia Cutis Congenita: Bart's Syndrome?

Cristiane Benvenuto, MD, Christine K. Kraemer, MD, Ricardo L. Kruse, Tania F. Cestari, MD, PhD

Disclosures

Skinmed. 2003;2(5) 

A boy was born at term to a 39-year-old mother after an uneventful pregnancy. On examination, soon after birth, he presented an erythematous ulcerated lesion, covered by a thin membrane, affecting the right leg and foot. The borders of the ulcer showed active granulation and small superficial vessels could be visualized underlying the defect. His left hallux was hypoplastic with anonychia. All other foot nails were dystrophic (Figure 1). Other than the skin defect, the child had no added defects or abnormalities. The histopathology of a biopsy taken from the periphery of the lesion demonstrated dermal-epidermal junction detachment, suggestive of epidermolysis bullosa (EB) (Figure 2). A study of the pedigree of his family revealed, including the patient, eight affected members, four women (his sister, his mother, his mother's mother, and his mother's half-sister) and four men (the patient himself, his two first cousins, and his mother's grandfather) (Figure 3). The patient's mother reported the same problem at birth, affecting the same leg, and showed no surprise when the physicians gave her the baby. She, and both of the patient's cousins, had active lesions of epidermolysis bullosa, the mother on her legs and the two cousins on their hands, caused by trauma (Figure 4). The patient's 12-year-old sister also had aplasia cutis congenita (ACC) (with similar lesions on the right leg) and EB. The management was conservative, and the patient was maintained under careful monitoring, with progressive healing of the lesion. After 2 months, reepithelization was complete and milia were prominent over the scar (Figure 5). On the 1-year follow-up exam, the child presented normal physical and neurologic development, without new cutaneous lesions except those induced by skin fragility just like his older sister and all affected family members.

Right leg and foot showing an erythematous ulcerated lesion and a hypoplastic hallux with anonychia.

Biopsy histopathology: detachment of the dermalepidermal junction.

Pedigree of the patient's family with eight affected members: the patient himself, his sister, his mother, his mother's mother, his mother's half-sister, his two first cousins (who were brothers), and his mother's mother's father.

Patient's mother's right leg: active lesion of epidermolysis bullosa resultant from local trauma.

Right leg and foot after 3 months of progressive healing of the lesion: complete reepithelization and prominent milia over the scar.

Epidermolysis bullosa is a rare inherited disorder characterized by increased skin fragility and blister formation.[1] The term comprises a heterogeneous group of mechanobullous diseases that differ with regard to genetic, clinical, and ultra structural characteristics.[1] At least 17 types of EB have been defined.[2] Using electron microscopy, the level of cleavage can be determined, allowing the classification among three different presentations. The separation occurs in the lamina lucida in junctional EB, below the lamina densa in the dystrophic variant, and within the epidermis in EB simplex.[1] Three autosomal dominant inherited forms of dystrophic EB are classically described, namely the Cockayne-Touraine type, the Pasini type, and Bart's syndrome.[3] All three types exhibit similar optical and electron microscopic features: blisters arise in the most superficial region of the dermis, immediately beneath the lamina densa of the dermal-epidermal junction, where anchoring fibrils are normally located.[3] Bart's syndrome is clinically characterized by congenital localized absence of skin, oral mucosal lesions, marked improvement after puberty, and minimal residual scarring in affected adults.

ACC, which may be associated with EB, was first reported in 1767. It is a rare condition characterized by well-circumscribed areas of congenital absence of skin, most commonly affecting the scalp with small, single, midline, posterior ulcers.[4,5,6] There is no sex predilection and the malformation may be limited to the epidermis, involve the full thickness of the skin, or include bone defects as well.[1,7,8,9,10] Histologically, there is an absence of epidermis (without inflammation), rudimentary or absent appendageal structures, and a decrease of elastic fibers in the dermis.[5] The diagnosis is mainly clinical and includes nine different groups, depending on the extension of compromising, inheritance, and associated findings.[10] Group 6, which is associated with EB, can be divided into two types: 1) localized blistering with autosomal dominant or recessive inheritance; and 2) widespread skin fragility with congenital abnormalities and autosomal recessive inheritance. There is no unifying theory explaining the origin of ACC because it is a physical finding denoting only that a disruption of the skin development has occurred in uterus.[10] The causes of this disruption vary and include genetic factors, teratogens, compromised skin vasculature, and trauma.[10]

The association of EB and ACC was first described in 1966.[11] The syndrome consists of ACC of the lower extremities, a mild blistering disorder of the hands and feet, oral mucosal lesions, and nail dystrophy. It usually shows marked improvement after puberty and minimal residual scarring in affected adults, keeping skin fragility throughout life.[7,12] One of the theories to explain the absence of skin in these patients is that mechanical trauma could occur from fetal movements, such as kicking, leading to in uterus blistering with subsequent erosions. This might also explain the preponderance of lower-extremity lesions.[10] The original paper[11] described a family with 26 affected members. Eight of them had blistering and nail dystrophy resembling Cockayne-Touraine type, but the skin defects healed without scarring. One member had only blisters, and three others presented only nail abnormalities. As at that time no histologic examination of blisters was reported,[10] the term Bart's syndrome has been used from then on, being associated with simple -- which probably was the case described by Bart at that time -- junctional and dystrophic EB.[1,8]

The continued use of the term Bart's syndrome to describe ACC of the extremities associated with mild blistering is problematic, since it is now evident that several forms of EB with different levels of blistering can have these findings (such as ACC with EB simplex and autosomal dominant EB dystrophica).[1,3] In such patients, efforts should be made to further characterize the type of EB with electron microscopy, continued clinical observation, and detailed use of the clinical history to characterize the form of inheritance.[10]

Management of ACC is controversial and may be conservative, surgical, or a combination of both, depending on the extension and location of the lesion.[9] Obstetricians and pediatricians must be familiar with the clinical findings described here to avoid the common suspicion of birth trauma (and all the legal aspects involved) and intempestive therapies.[8] Careful monitoring and conservative management are appropriate including protection of the skin with the use of atraumatic dressings, since lesions tend to heal spontaneously in a few days, leaving a residual scar.[4,13] When associated with EB, attention should be given to prevention of trauma. The triad of wound management, nutritional support, and infection control is the key for successful management of all EB patients.[14] Some authors have already tried topical, dietetic, and systemic treatments without positive results.[12]

The familial history of the case reported here, with three consecutive generations affected, confirms the autosomal dominant inheritance of the disease, calling attention to the importance of genetic counseling, considering its high penetrance.[5,7,8,15]

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