Counselling in Incontinentia Pigmenti (IP2) families: useful information from X-inactivation studies. M.L. Bonduelle, W. Lissens, I. Rayen, L. De Raeve, I. Liebaers. Dutch-speaking Brussels Free University, Brussels, Belgium.

   Incontinentia Pigmenti (IP2) is an X-linked dominant neurocutaneous disorder with prenatal male lethality. Affected females display a progressive erythematous and vesicular skin eruption soon after birth evolving through different stages and frequently accompanied by dental and retinal abnormalities. Central nervous system is affected in a variable degree. Expression is highly variable even within families. Penetrance approaches 100%, but in families with minimal symptoms counselling remains sometimes difficult. Selection against mutant alleles in blood leukocytes is a consistent feature in IP2 families (98% in multigenerational IP2 and 85% in new mutations). In families with apparently de novo mutations and minimal symptoms such as dental anomalies in the mother, X inactivation studies can help to make the diagnosis and determine the parental origin of the mutation. In 4 IP2 families where the mother had minimal or no symptoms we determined the parental origin of the new mutation through X inactivation studies for the M27beta locus with restriction enzymes MspI and HpaII. Three new mutations had a maternal and 1 had a paternal origin. Complete skewing in the patients and random X-inactivation in the healthy mother could be used as an additional argument for considering the mother not being a carrier. Unless germline mosaicism would have occurred, these data could be used to reassure the couple and minimalise the recurrence risk for IP2.