OMIM ID:
Incontinentia Pigmenti
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
This is primarily a disorder of skin, teeth, hair, and the central nervous system but 35% of patients have important ocular features. The iris is variably atrophic and has pigmentary anomalies often with posterior synechiae. Nystagmus, strabismus, and limited vision are often present. The majority (up to 90%) of individuals have significant retinal disease. The retinal vascular pattern is anomalous with tortuosity in some areas and absence of vessels in others. Preretinal fibrosis and retinal detachments may suggest the presence of a retinoblastoma. Cataracts are common in patients who have a retinal detachment and some patients have microphthalmia. The retinal pigment epithelium is often abnormal with various-sized patches of sharply demarcated depigmentation. Cases with uveitis, papillitis and chorioretinitis have been observed and it has been suggested that the observed retinal and choroidal changes result from prior inflammatory disease, perhaps even occurring in utero. There is a great deal of asymmetry in the clinical findings in the two eyes.
Systemic Features
Skin changes consisting of erythematous eruptions in a linear pattern are often present at birth and this may be followed by a verrucous stage. The acute, early findings of inflammatory disease eventually subside, ultimately resulting in pigmentary changes that appear in a ‘marbled pattern’ in young adults. Hypodontia and anodontia may be present. Alopecia and CNS abnormalities are found in nearly half of patients. Skeletal and structural deformities are common in patients with severe neurological deficits. The only sign of this disorder in adult women may be a whorled pattern of scarring alopecia.
As many as 30% of patients have neurological features which may be present in the neonatal period. Seizures of various types occur in 30% of patients. MRI findings include periventricular and subcortical white matter changes, as well as corpus callosum hypoplasia, cerebral atrophy, and cerebellar hypoplasia.
Genetics
Inheritance
The majority of evidence suggests that this is an X-linked dominant disorder with lethality in males although sporadic cases occur. The mutation occurs as a genomic rearrangement of the IKK-gamma gene, also known as NEMO (IKBKG) located at Xq28. There is evidence from skin cultures that cells with the mutant X chromosome inactivated are preferentially viable. It has been proposed that cells with the mutant bearing X chromosome as the active one are gradually replaced by those in which the normal X chromosome is active accounting for the post-natal course of the skin disease.
Pedigree
X-linked dominant, mother affected
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.