Incontinentia pigmenti (IP, Bloch-Sulzberger syndrome)

Incontinentia Pigmenti (IP) is a rare multisystem disorder classified as an ectodermal dysplasia with variable abnormalities of the skin, hair, nails, teeth, eyes, and central nervous system. The skin of IP patients shows vesicular, verrucous, and pigmented macular lesions. In addition, the patients have dental, ocular, central nervous system, and structural anomalies (Gorlin et al, 1990). IP is an X-linked dominant disorder and has been shown to be due to mutations in IKK-gamma (NEMO) gene located in Xq28 (Smahi et al, 2000). The affected individuals are mostly females (97% of the patients). It is assumed that males with the mutation usually do not survive through gestation (Macey-Dare et al, 1999).

In studies on dental anomalies, over 90% of the patients have hypodontia, mostly classified as severe (6 or more teeth missing), microdontia (generalized microdontia or peg-shaped teeth), macrodontia (extra cusps in the posterior teeth), delayed eruption of permanent teeth, or taurodontism (Gorlin et al, 1990; Macey-Dare et al, 1999). Incidence of congenitally missing teeth has been reported to be as high as 43%; in addition, 30% of the patients have conical teeth (Macey-Dare et al, 1999). Tooth anomalies are seen both in primary and permanent dentitions, but the permanent dentition is usually more severely affected.

Hypohidrotic ectodermal dysplasia and immune deficiency (HED-ID)

A novel form of EDA, together with immunodeficiency, segregates as an X-linked recessive trait (Zonana et al, 2000) (D÷ffinger et al, 2001). Clinical findings: hypohidrosis and abnormal dentition, are similar to those in other forms of EDA. Tooth agenesis occurs both in primary and in permanent dentitions. Hypodontia, oligodontia, and conical teeth are the forms of tooth manifestation. Affected males manifest dysgammaglobulinemia and suffer significant mortality from infections. Female carriers show no clinical signs of immunodeficiency but have other manifestations including hypodontia and conical teeth. Mutations in the IKK-gamma (NEMO) gene have been found in HED-ID patients, and thus HED-ID is allelic to incontinentia pigmenti. IKKg is required for activation of NFkB, a transcription factor transducing TNF signaling. NFkB was recently shown also to transduce signaling via ectodysplasin/ Edar, which presumably explains the phenotypic similarities between EDA and HED-ID (Kumar et al, 2001; Koppinen et al, 2001).

IKK-gamma has also been inactivated in mice (Makris et al, 2000; Schmidt-Supprian et al, 2000). Male mice with a null allele of IKK-gamma in X-chromosome die in midgestation (embryonic days 13-15) because of massive apoptosis in the liver. Hemizygous female mice are viable but develop a dermatopathy characterized by keratinocyte hyperproliferation and increased apoptosis that leads to early lethality or survival through selection of wildtype keratinocytes that have inactivated the X chromosome with mutant IKK-gamma. Defects of dentition in these mice has not been reported.

Text partially adapted from Sirpa Arte: Phenotypic and genotypic features of familial hypodontia. Dissertation, Institute of Dentistry, University of Helsinki, Finland, 2001.


Jackson Mouse Genome Database Transgene Database OMIM

Text last edited 09.10.2003 by P.N. , page last created 10.12.2004 by P.N.