BLISTER FORMING SKIN DISORDERS

 

Fetal skin denudation is a rare phenomenon because the occurrence of bullae in blister forming skin disorders usually occurs postnatally.

Blister forming skin disorders that have been reported antenatally include aplasia cutis and bullous ichthyosiform erythroderma (epidermolytic hyperkeratosis) and epidermolysis bullosa.(1).

  • Aplasia Cutis Congenita (ACC):
    It is believed that the large skin defects seen in cases of ACC are probably due to in utero skin peeling secondary to fetal movement (2).
    The presence of high levels of amniotic fluid alpha-fetoprotein in cases of epidermolysis bullosa further suggests that in utero blistering and skin denudation does occur (3).
    Aplasia cutis is a feature of Adams-Oliver syndrome.
  • Bullous ichthyosiform erythroderma (4).
    This condition has been prenatally diagnosed through skin biopsies at fetoscopy and from cell in the amniotic fluid.
  • Epidermolysis Bullosa (5,6).  Junctional Epidermolysis Bullosa (JEB) is a group of inherited mechanobullous diseases having an autosomal recessive mode of inheritance, and characterized by  blister formation of the lamina lucida of the epidermal basement layer, and hypoplastic hemidesmosomes. EB-PA is a sub-type  of JEB, associated with congenital pyloric atresia. It is known to be caused by the ITGA6 or ITGB4 genes encoding for the integrin alpha 6 or beta 4 subunit respectively  (7,8).

 

ULTRASOUND
  • Snowflake Sign (1).
    Small echogenic particles in the amniotic fluid early in pregnancy. It may be impossible to distinguish from vernix which usually appears later in pregnancy. These particles, when present in association with an elevated maternal serum alpha-fetoprotein, or when there is a family history of a relevant skin disorder suggests that the snowflakes are due to a skin disorder.

 

 

 

REFERENCES
  1. Meizner I, Carmi R. The snowflake sign. A sonographic marker for prenatal detection of fetal skin denudation. J Ultrasound Med 1990;9:607-609.
  2. Carmi R, Sofer S, Karplus M et.al. Aplasia cutis congenita in two sibs discordant for pyloric atresia. Am J Med Genet 1982;11:319.
  3. Leschot NJ. Letter to the editor: Congenital skin defects and gastrointestinal atresia. Am J Med Genet 1983;15:157.
  4. Golbus MS, Sagebiel RW, Filly RA et.al. Prenatal diagnosis of congenital bullous ichthyosiform erythroderma by fetal skin biopsy. N Engl J Med 1980;302:93.
  5. Yacoub T, Campbell CA, Gordon YB et.al. Maternal serum and amniotic fluid concentrations of alpha-fetoprotein in epidermolysis bullosa simplex. Br Med J 1979;1:307.
  6. De Jenlis B De, Deruelle P, Kacet N . et.al. Prenatal findings in epidermolysis bullosa with pyloric atresia in a family not known to be at risk. Ultrasound Obstet Gynecol 2005;25:607-609.
  7. Ruzzi L, Gagnoux-Palacois L, Pinola M et.al. A homozygous mutation in the integrin alpha 6 gene in junctional epidermolysis bullosa with pyloric atresia. J Clin Invest 1997;99:2826-2831.
  8. Vidal F, Aberdam D, Miquel C et.al. Integrin beta 4 mutations associated with junctional epidermolysis bullosa with pyloric atresia..Nat Genet 1995;10:229-234.