Duplication at Xq28 involving IKBKG is associated with progressive macrocephaly, recurrent infections, ectodermal dysplasia, benign tumors, and neuropathy.
Duplications on Xq28 are common, although quite variable in size, but usually include the MECP2 gene. Here, we present a patient with a unique, small, 167-kb duplication at Xq28, not including MECP2. The most important gene in the duplicated region was IKBKG, mutations in which can cause a variety of distinct syndromes. Our patient's symptoms overlapped with different IKBKG-associated phenotypes, including hypohidrotic ectodermal dysplasia, incontinentia pigmenti, immunodeficiency, recurrent isolated invasive pneumococcal disease and anhidrotic ectodermal dysplasia with immunodeficiency, osteopetrosis, and lymphedema. In addition, she also had peripheral neuropathy, gastroparesis and various benign tumors, but no intellectual disability. Mixed syndromal presentation in several patients with IKBKG defect implies that IKBKG-related phenotypes are more like a spectrum, rather than distinct syndromes. We also suggest our patient's multisystem phenotype to be a novel contiguous gene syndrome, in which the key features include immune deficiency, macrocephaly, skin abnormalities, gastroparesis, peripheral small-fiber neuropathy, and benign tumors.
Department of Pediatrics, Tulane University Medical School, Hayward Genetics Center, New Orleans, Louisiana, USA.
Ellyze
E
van Asbeck
Arivudainambi
A
Ramalingam
Chris
C
Dvorak
Tian-Jian
TJ
Chen
Eva
E
Morava
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D058674:Chromosome Duplication; D041321:Chromosomes, Human, X / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004476:Ectodermal Dysplasia / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006391:Hemangioma / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics*; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000235:genetics; D058627:Megalencephaly / Q000175:diagnosis* / Q000235:genetics; D009442:Neurilemmoma / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D011115:Polyneuropathies / Q000175:diagnosis* / Q000235:genetics
C491731:IKBKG protein, human; D051550:I-kappa B Kinase