Alternative titles; symbols
SNOMEDCT: 723553000; ORPHA: 79411; DO: 0111345;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3p21.31 | Transient bullous of the newborn | 131705 | Autosomal dominant; Autosomal recessive | 3 | COL7A1 | 120120 |
A number sign (#) is used with this entry because transient bullous dermolysis of the newborn (TBDN) is caused by heterozygous or compound heterozygous mutation in the COL7A1 gene (120120) on chromosome 3p21.
Autosomal dominant and autosomal recessive epidermolysis bullosa dystrophica (131750, 226600) are allelic disorders.
Transient bullous dermolysis of the newborn (TBDN) is a rare form of dystrophic epidermolysis bullosa (DEB) that presents with neonatal skin blistering but usually improves markedly during early life and 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 (summary by Fassihi et al., 2005).
Hashimoto et al. (1985) first described this disorder in an African American male delivered by cesarean section who developed large bullae on his extremities and in other friction areas soon after birth. The bullae healed rapidly, leaving hypopigmentation, but no scars or milia. Occasional new lesions continued to appear for 4 months but not after. Reexamination 12 months later showed a normal healthy infant with only residual hypopigmentation in some of the previously involved areas. Histologic and electron microscopic examinations revealed a subepidermal bulla that was ultrastructurally a subbasal lamina separation associated with collagenolysis and damage to the anchoring fibrils. There was no significant family history.
Hashimoto et al. (1989) reported 2 additional cases of transient bullous dermolysis of the newborn. One was a white boy who had normal skin at birth, but developed multiple blisters soon after. The oral mucous membranes were not affected. All lesions healed within 4 months without scars but with many milia. No blisters or milia were apparent at age 17 months. The second patient was a Japanese girl who showed extensive denudation of her hands at birth. Generalized blisters and involvement of the oral mucous membrane developed. Blistering stopped within 1.25 months, and all lesions healed without scars. The blisters were subepidermal in both cases. Electron microscopy revealed collagenolysis, diminution or loss of anchoring fibrils, and stellate inclusions in dilated rough endoplasmic reticulum in the keratinocytes of the lower epidermis.
Fine et al. (1990) also described cases. The usual finding is blistering during the first months of life but none after age 1 year. Immunohistochemical studies showed granular basilar keratinocyte perinuclear intracytoplasmic deposits of COL7A1, rather than exclusively linear basement membrane deposits. Fine et al. (1990) proposed a defect in the intracytoplasmic packaging or in the transport of type VII collagen within basilar keratinocytes.
Fine et al. (1991, 1993) performed longitudinal studies of 9 patients from 4 families with transient bullous dermolysis of the newborn. Clinical features included the development of generalized blisters and skin erosions at birth followed by milia formation. Nail dystrophy was also apparent, but nails tended to regrow normally. In 3 families, blister formation disappeared by age 6 months; in the fourth family, blister activity became minimal within the first 2 years of life although some lesions continued to occur into the thirties. During the blistering period, type VII collagen was retained within basilar keratinocytes rather than incorporated into the dermal-epidermal junction. However, following complete cessation of or marked reduction in the extent of blister formation, type VII collagen was expressed in normal intensity in linear distribution along the dermal-epidermal junction, identical to that observed in normal human skin. Fine et al. (1991, 1993) concluded that the temporary presence of mechanical fragility and blister formation reflected a delay in transport and integration of type VII collagen from basilar keratinocytes into skin basement membrane.
McCollough et al. (1991) reported an infant with this disorder. She was born with blisters on the hands, feet, trunk, face, and oral mucosa which healed without scarring. By age 6 months the patient had developed only an occasional blister. The mother stated that during the first 6 months of life she also had had blisters, which spontaneously resolved at 6 months of age. Intraepidermal type VII collagen was demonstrated immunohistologically.
Fassihi et al. (2005) reported autosomal dominant TBDN in a proband, his father, and his paternal grandfather. The authors performed a skin biopsy analysis in the affected individuals, which showed persistence of some intraepidermal type VIII collagen, suggesting that despite the clinical resolution, some abnormalities of type VII collagen processing and secretion may persist.
The transmission pattern of TBDN in the family reported by Fine et al. (1993) and Christiano et al. (1997) was consistent with autosomal dominant inheritance.
In affected members of a family with autosomal dominant transient bullous dermolysis of the newborn reported by Fine et al. (1993), Christiano et al. (1997) identified a heterozygous mutation in the COL7A1 gene (120120.0039).
In a patient with TBDN, Hammami-Hauasli et al. (1998) identified compound heterozygosity for 2 mutations in the COL7A1 gene (G2251E, 120120.0014; G1519D, 120120.0015). Heterozygous carriers of the G2251E allele had normal skin but isolated toenail dystrophy (607523).
In affected males in 3 generations of a family segregating TBDN, Fassihi et al. (2005) identified a heterozygous mutation in the COL7A1 gene (120120.0044).
Christiano, A. M., Fine, J.-D., Uitto, J. Genetic basis of dominantly inherited transient bullous dermolysis of the newborn: a splice site mutation in the type VII collagen gene. J. Invest. Derm. 109: 811-814, 1997. [PubMed: 9406826] [Full Text: https://doi.org/10.1111/1523-1747.ep12341013]
Fassihi, H., Diba, V. C., Wessagowit, V., Dopping-Hepenstal, P. J. C., Jones, C. A., Burrows, N. P., McGrath, J. A. Transient bullous dermolysis of the newborn in three generations. Brit. J. Derm. 153: 1058-1063, 2005. [PubMed: 16225626] [Full Text: https://doi.org/10.1111/j.1365-2133.2005.06873.x]
Fine, J. D., Horiguchi, Y., Stein, D. H., Esterly, N. B., Leigh, I. M. Intraepidermal type VII collagen: evidence for abnormal intracytoplasmic processing of a major basement membrane protein in rare patients with dominant and possibly localized recessive forms of dystrophic epidermolysis bullosa. J. Am. Acad. Derm. 22: 188-195, 1990. [PubMed: 2104504]
Fine, J. D., Johnson, L. B., Cronce, D., Wright, J. T., Leigh, I. M., McCollough, M., Briggaman, R. A. Intracytoplasmic retention of type VII collagen and dominant dystrophic epidermolysis bullosa: reversal of defect following cessation of or marked improvement in disease activity. J. Invest. Derm. 101: 232-236, 1993. [PubMed: 8345225] [Full Text: https://doi.org/10.1111/1523-1747.ep12364899]
Fine, J. D., Johnson, L. B., Leigh, I. M., Briggaman, R. A. Intracytoplasmic retention of type VII collagen in dominant dystrophic epidermolysis bullosa: ultrastructural demonstration of reversal of defect following cessation of or marked improvement of disease activity. (Abstract) Clin. Res. 39: 323A only, 1991.
Hammami-Hauasli, N., Raghunath, M., Kuster, W., Bruckner-Tuderman, L. Transient bullous dermolysis of the newborn associated with compound heterozygosity for recessive and dominant COL7A1 mutations. J. Invest. Derm. 111: 1214-1219, 1998. [PubMed: 9856844] [Full Text: https://doi.org/10.1046/j.1523-1747.1998.00394.x]
Hashimoto, K., Burk, J. D., Bale, G. F., Eto, H., Hashimoto, A., Kameyama, K., Kanzaki, T., Nishiyama, S. Transient bullous dermolysis of the newborn: two additional cases. J. Am. Acad. Derm. 21: 708-713, 1989. [PubMed: 2681282] [Full Text: https://doi.org/10.1016/s0190-9622(89)70241-3]
Hashimoto, K., Matsumoto, M., Iacobelli, D. Transient bullous dermolysis of the newborn. Arch. Derm. 121: 1429-1438, 1985. [PubMed: 3901931]
McCollough, M. L., Grimwood, R. E., Grabski, W. J. Dominant dystrophic epidermolysis bullosa with intraepidermal type VII collagen. (Letter) J. Am. Acad. Derm. 24: 512 only, 1991. [PubMed: 2061461] [Full Text: https://doi.org/10.1016/s0190-9622(08)80088-6]