Incontinentia Pigmenti Flashcards
Incontinentia Pigmenti (IP)
The condition describes is Incontinentia Pigmenti (IP), an X-linked male lethal trait.
- In such conditions one sees fewer than expected males in a given pedigree, as ½ of male fetuses (those affected) are lost.
- For an X-linked lethal trait, approximately 1/3rd of cases are new mutations.
- There is no cytogenetic abnormality associated with IP.
- Chromosome analysis of fibroblasts demonstrates an abnormality in approximately 40% of cases of Hypomelanosis of Ito, a related but clinically distinct disorder.
- Affected females can have unaffected males and affected and unaffected females.
Incontinentia Pigmenti
- IKBKG (aka NEMO)
- XLD (most male fetuses miscarry)
Major:
- Four stages of skin changes:
- erythema->blister->hyperpigmented streaks->atrophic skin patches.
Minor:
- hypo/andontia, small or malformed teeth, alopecia, woolly hair, nail ridging or pitting, retinal neovascularization causing retinal detachment.
- ID is rare.
Incognentia Pigmenti
Incontinentia Pigmenti
Responsible gene: IKBKG (aka NEMO)
Protein: NF-kappa B essential modulator
Cytogenetic locus: Xq28
The most efficacious molecular genetic testing approach is single-gene testing.
Molecular Tests: Southern blot: Exon 4-10 deletion (80%).
- Skewed X inactivation in females (not diagnostic).
Disease Mechanism: Lack of NF-kappa beta activation leads to cells that are sensitive to proapoptotic signals and apoptosis easily.
- Treatment/Prognosis: Regular retinal exams in first 1-2 yrs. Cosmetic dentistry. Normal life expectancy.
A 3-year-old girl has hypodontia, alopecia, and mild developmental delay. Examination reveals
hyperpigmented hyperkeratotic streaks. Her sister has severe developmental delay with seizures.
Her mother has partial adontia and atrophic scalp hair.
One sees fewer than expected males in affected families.
