Hypohidrotic ectodermal dysplasia and Hypomelanosis of Ito in a girl with a de novo t(X;13)(q13;p11.2). S.J. Orlow1, R. Marion2, C. Duncan3, H. Gu3, M. Genovese3, E. Jenkins3, A. Shanske2. 1) Dermatology, NYU Medical Center, New York, NY; 2) Pediatrics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; 3) Institute for Basic Research, Staten Island, NY.
Hypohidrotic ectodermal dysplasia (HED)is caused by mutations of the EDA1 gene at Xq12-13.1 that is critical for the morphogenesis of epidermal derivatives.Heterozygous women may show mild abnormalities of ectodermal derivatives and fully manifesting females look like affected males.Hypomelanosis of Ito(HI)is a heterogeneous disorder characterized by macular hypopigmented whorls, streaks, and patches.Abnormalities of the CNS occur frequently.Mosaicism for different aneuploidies is a common finding and often involves the X chromosome.We evaluated a 5-year-old female with features of both HED and HI.Her physical examination at 4 10/12 years of age revealed an unstigmatized youngster whose height was 104 cm (50%); weight 16 kg (10-25%)and HC 51 cm (50%). She had maxillary hypoplasia,low nasal bridge,conical teeth with increased spacing,periorbital wrinkling,patchy alopecia,and sebaceous hypoplasia over the bridge of her nose consistent with HED and striped hypopigmentation on her trunk following Blaschko's lines consistent with HI.Short term whole blood lymphocyte cultures revealed an apparently balanced de novo X;13 translocation in 40 cells analyzed with a karyotype of 46,X,t(X;13)(q13;p11.2).The same nonmosiac translocation was identified in fibroblast cultures derived from hypopigmented and pigmented areas of skin. Replication X studies using a BrdU terminal pulse showed an inactive normal X chromosome in 100%of blood cells but were unsuccessful in fibroblasts.
We conclude that our patient is a fully manifesting female with HED because the translocation affects the EDA1 gene.Functional disomy has been proposed as a likely mechanism because of the skewed X-inactivation observed in most cases.PCR analysis of DNA extracted from uncultured cells show that a more balanced pattern of inactivation can be observed in these cells.Partial functional disomy in the fibroblast cell lineage may also be responsible for the HI in our patient.