A Case of a Surviving Male Infant with Incontinentia Pigmenti: DISCUSSION

13 Feb
2011

Although a case resembling IP was first described by Garrod in 1906, IP was characterized as a clinical syndrome by Bloch in 1926. In 1927, Sulzberger reported Bloch’s case in details, and then proposed as Bloch-Sulzberger’s disease.

In general, boys with single X chromosomal gene abnormality are so severely affected as to be lethal in utero, therefore there is an increased incidence of spontaneous abortion in affected women, pre­sumably of male fetuses.

The major cause of IP is loss-of-function mutation of NEMO protein, most consisting of a deletion of exons 4 ~ 10 in heterozygous females. The gene mutated in IP is mapped to Xq28 and encodes the NEMO. NEMO is a regulatory component of the IKB kinase complex required for NF- kB activation. Therefore, it is central to many immune, inflam­matory responses, and apoptotic pathways. Disrup­tion of NEMO gene leads to diminished NF- kB activity which increases the susceptibility of cells to apoptosis. cialis canadian pharmacy

It is quite rare for male patients with IP to survive. Survival occurs in approximately 2~3% of all the reported cases. It can be explained by three potential mechanisms: abnormal karyotype (Kline­felter’s syndrome, 47, XXY), hypomorphic muta­tions, and somatic mosaicism. The third is the most reliable explanation for the survival of male patients. It results from a postzygotic mutation oc­curring during the blastocyst stage of embryogenesis and does not completely abolish NF- К activity, which allows survival. Thus, the presence of somatic mosaicism results in mild features of known genetic disorders, and better outcomes afterward. Skin findings of live born male patients are generally not greater than those in affected females and many male patients have disease expression limited to cutaneous involvement of one or two limbs. According to Scheuerle, live born males with IP are inferred to be of generally good health and not at increased risk of neonatal or infantile mortality, because multiple hospitalizations or life threatening illness have not been reported. The clinical features of IP are associated with ectodermal tissue abnormalities including skin, hair, nails, teeth, eyes, and central nervous system. Skin finding is characterized by typical linear lesions subdivided into 4 stages with variable timings: Perinatal inflam­matory vesicles (stage 1), verrucous patches with hyperkeratosis (stage 2), a distinctive pattern of streaky hyperpigmentation following Blaschko’s lines (stage 3), and finally atrophy, hairlessness, and scarring (stage 4). These represent the death of cells carrying the mutated gene along lines of embryonic cellular migration. However, some of the stages may occur concurrently with others, or not at all.

In addition, females who carry loss-of-function mutations would be expected to often have severe clinical signs, including neurologic: spastic paralysis, convulsion, and mental retardation; ophthalmolo­gic: strabismus, cataracts, microphthalmos, cataract and optic atrophy; and odontologic defects: partial anodontia, delayed impaction, and crown malfor­mations, presenting at birth or during the first few weeks of life. generic viagra online

The severity of IP is related to ocular and neurological impairment, in particular, blindness and psychomotor retardation, not skin lesions. The latter generally disappear spontaneously, and no treatment is necessary other than the control of secondary infection. However, other complications should be sought carefully and, if possible, treated quickly as soon as the diagnosis of IP is established. Also, urgent consultations with ophthalmic, neu­rologic and dental subspecialists are often needed.

In conclusion, in a survival case of male infant with IP, careful evaluation, chromosomal analysis, and family counseling should be performed to rule out alternative diagnoses and for better clinical outcomes.

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