16 - incontinentia pigmentosa

Incontinentia Pigmenti (IP) is a genetic disorder that affects the skin, hair, teeth, and nails. It is also known as Bloch Sulzberger syndrome, Bloch Siemens syndrome, melanoblastosis cutis and naevus pigmentosus systematicus.

This disorder was first reported by Bruno Bloch, a German dermatologist in 1926 and Marion Sulzberger, an American dermatologist in 1928.

The skin lesions evolve through characteristic stages:

1. blistering (from birth to about four months of age),
2. a wart-like rash (for several months),
3. swirling macular hyperpigmentation (from about six months of age into adulthood), followed by
4. linear hypopigmentation.

chinese letter pattern of hyperpigmentation seen in incontinentia pigmentosa

Alopecia, hypodontia, abnormal tooth shape, and dystrophic nails are observed. Some patients have retinal vascular abnormalities predisposing to retinal detachment in early childhood. Cognitive delays/mental retardation are occasionally seen.

The diagnosis of IP is established by clinical findings and occasionally by corroborative skin biopsy. Molecular genetic testing of the IKBKG gene (chromosomal locus Xq28) reveals disease-causing mutations in about 80% of probands. Such testing is available clinically. In addition, females with IP have skewed X-chromosome inactivation; testing for this can be used to support the diagnosis.

IP is inherited in an X-linked dominant manner. IP is lethal in most, but not all, males. A female with IP may have inherited the IKBKG mutation from either parent or have a new gene mutation. Parents may either be clinically affected or have germline mosaicism. Affected women have a 50% risk of transmitting the mutant IKBKG allele at conception; however, most affected male conceptuses miscarry. Thus, the expected ratio for liveborn children is 33% unaffected females, 33% affected females, and 33% unaffected males. Genetic counseling, prenatal testing, and preimplantation genetic diagnosis is available.

In females, the cells expressing the mutated IKBKG gene due to lyonization selectively die around the time of birth so the X-inactivation is extremely skewed.