Long-term follow-up of neurological manifestations in a boy with incontinentia pigmenti

Abstract

Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis confined to females. It is usually lethal in males. However, the survival of some males has been reported in literature. We describe a long follow-up case of a 12-year-old male with IP and a normal karyotype but a genomic deletion of the NEMO gene in the Xq28 position in the form of somatic mosaicism. The patient showed severe ophthalmic abnormalities and neurological manifestations characterised by very mild cerebellar ataxia and a history of epilepsy that was severe at the beginning with West syndrome, become moderate overtime and is now resolved. Despite these neurological manifestations, probably related to the presence of at least some mutated cells in his brain, the long-term follow-up in this patient demonstrated good neurological and cognitive outcome.

Neonatal presentation of incontinentia pigmenti with a family history extending over four generations – A case report

“…The patient showed severe ophthalmic abnormalities and neurological manifestations characterized by mild cerebellar ataxia and a history of epilepsy that was severe at the beginning with West syndrome, become moderate overtime and gradually resolved. Despite these neurological manifestations the longterm follow-up in this patient as reported by the authors, demonstrated good neurological and cognitive outcome [14]. It should be noted here that not all IP patients may have such an outcome.…”

Incontinentia pigmenti in a male (XY) infant with long‐term follow up over 8 years

“…Somatic mosaicism refers to the occurrence of two genetically distinct populations of cells within an individual. On the other hand, hypomorphic or milder mutations in the IKBKG/NEMO gene, which result in the attenuation of NEMO function, can cause hypohidrotic ectodermal dysplasia with severe immunodeficiency (ectodermal dysplasia with immunodeficiency) . Large frame‐shift or deletion mutations that completely impair NEMO function lead to a lethal condition in male fetuses …”

“…On the other hand, hypomorphic or milder mutations in the IKBKG/ NEMO gene, which result in the attenuation of NEMO function, can cause hypohidrotic ectodermal dysplasia with severe immunodeficiency (ectodermal dysplasia with immunodeficiency). 8 Large frame-shift or deletion mutations that completely impair NEMO function lead to a lethal condition in male fetuses. 9 A large deletion of exons 4-10 is found in approximately 80% of IP patients, whereas a small proportion of patients demonstrate mutations such as small nucleotide substitution, deletion and insertion.…”

Human Genetics and Clinical Aspects of Neurodevelopmental Disorders

“…De novo mutations, germline mosaicism and other complexities Although this concept of somatic mosaicism has been in the literature for many years [131][132][133][134][135], it is really only recently that more people are beginning to realize that it might be much more extensive in humans than previously thought [23,[136][137][138][139][140][141][142][143][144][145][146][147][148][149]. In fact, hardly anything is truly known regarding the extent of somatic mosaicism in humans and its effect on phenotype in even well studied diseases.…”