Transient bullous dermolysis of the newborn in three generations

Abstract

Transient bullous dermolysis of the newborn (TBDN) is a rare form of dystrophic epidermolysis bullosa (DEB) that presents with neonatal skin blistering but which usually improves markedly during early life or even remits completely. Skin biopsies reveal abnormal intraepidermal accumulation of type VII collagen which results in poorly constructed anchoring fibrils and a sublamina densa plane of blister formation. The reason for the spontaneous clinical improvement is not known, but there is a gradual recovery in type VII collagen secretion from basal keratinocytes to the dermal-epidermal junction, with subsequent improvement or correction of anchoring fibril morphology. In this report, we describe TBDN occurring in three generations of the same family. Blistering occurred only during the first few months after birth, and all affected individuals were found to have a heterozygous glycine substitution mutation in exon 45 of the type VII collagen gene, COL7A1, designated G1522E. This mutation represents the third report of a pathogenic COL7A1 mutation in TBDN. Despite limited understanding of the disease mechanism in TBDN, this distinct form of DEB is important to recognize as it typically has a benign and self-limiting course. However, not all cases of DEB associated with intraepidermal type VII collagen are 'transient'. Genetic counselling in such patients therefore should be guarded until the pathophysiology of TBDN is better understood.

COL7A1 mutation G2037E causes epidermal retention of type VII collagen

“…2B). This pattern is a characteristic feature of DDEB and transient bullous dermolysis of the newborn; this is a rare form of dystrophic epidermolysis bullosa and also caused by COL7A1 mutations (Fassihi et al 2005). Patients with transient bullous dermolysis of the newborn present with neonatal skin blistering which usually improves markedly during early life or even remits completely.…”

Milia: A review and classification

“…Transient bullous dermolysis of the newborn is a rare, controversial condition characterized by neonatal trauma-induced blisters on the extremities, lasting approximately 2 months, and usually followed by milia. [128][129][130][131][132] A minority of cases demonstrate a positive family history, oral lesions, onychodystrophy, scarring, or hypopigmentation. Pathologic features include a sublamina densa split, damaged and decreased anchoring fibrils, dilated rough endoplasmic reticulum in basal keratinocytes, and stellate bodies containing procollagen 7 in basal keratinocytes.…”

“…Pathologic features include a sublamina densa split, damaged and decreased anchoring fibrils, dilated rough endoplasmic reticulum in basal keratinocytes, and stellate bodies containing procollagen 7 in basal keratinocytes. Several cases [129][130][131][132] have demonstrated COL7A1 gene mutations with autosomal dominant or recessive inheritance.…”

Autosomal dominant bullous dermolysis of the newborn associated with a heterozygous missense mutation p.G1673R in type VII collagen

“…1,2 It is characterized by blistering of the skin at birth in the setting of mechanical trauma, with subsequent improvement or complete resolution of symptoms over the ensuing months of life (OMIM 131705). Initial neonatal blistering can be widespread, involving the trunk and extremities.…”

“…Healing typically occurs without scarring, although permanent scarring has been reported. 2,3 Fewer than 30 cases of BDN have been reported in the literature since the identification of the disease in 1985. 4 The pathogenesis of the disease is poorly understood; however, mutations in the collagen VII gene (COL7A1) have been implicated.…”